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Acupuncture-Like Transcutaneous Electrical Nerve Stimulation (ALTENS) or Pilocarpine in Treating Early Dry Mouth in Patients Undergoing Radiation Therapy for Head and Neck Cancer

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ClinicalTrials.gov Identifier: NCT00656513
Recruitment Status : Completed
First Posted : April 11, 2008
Results First Posted : August 21, 2017
Last Update Posted : August 21, 2017
Sponsor:
Collaborators:
National Cancer Institute (NCI)
NRG Oncology
Information provided by (Responsible Party):
Radiation Therapy Oncology Group

Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Supportive Care
Conditions: Head and Neck Cancer
Xerostomia
Interventions: Drug: Pilocarpine
Procedure: ALTENS

  Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
ALTENS: Phase II Acupuncture-like transcutaneous electrical nerve stimulation (ALTENS) twice weekly for 12 weeks via a Codetron unit
Pilocarpine: Phase III 5mg pilocarpine by mouth 3 times a day for 12 weeks
ALTENS: Phase III Acupuncture-like transcutaneous electrical nerve stimulation (ALTENS) twice weekly for 12 weeks via a Codetron unit

Participant Flow:   Overall Study
    ALTENS: Phase II   Pilocarpine: Phase III   ALTENS: Phase III
STARTED   48   73   75 
COMPLETED   44 [1]   43 [1]   53 [1] 
NOT COMPLETED   4   30   22 
Protocol Violation                1                0                2 
Withdrawal by Subject                0                11                4 
Death                0                0                1 
Missing data                0                11                9 
Incomplete treatment                3                0                0 
Treatment completed outside of timeframe                0                3                1 
Missing baseline form                0                5                5 
[1] Subjects with data available for the primary analysis are considered to have completed the study.



  Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Eligible patients (i.e. without protocol violation)

Reporting Groups
  Description
ALTENS: Phase II Acupuncture-like transcutaneous electrical nerve stimulation (ALTENS) twice weekly for 12 weeks via a Codetron unit
Pilocarpine: Phase III 5mg pilocarpine by mouth 3 times a day for 12 weeks
ALTENS: Phase III Acupuncture-like transcutaneous electrical nerve stimulation (ALTENS) twice weekly for 12 weeks via a Codetron unit
Total Total of all reporting groups

Baseline Measures
   ALTENS: Phase II   Pilocarpine: Phase III   ALTENS: Phase III   Total 
Overall Participants Analyzed 
[Units: Participants]
 47   73   73   193 
Age 
[Units: Years]
Median (Full Range)
 60 
 (24 to 80) 
 59 
 (29 to 78) 
 58 
 (42 to 83) 
 58 
 (24 to 83) 
Sex: Female, Male 
[Units: Participants]
Count of Participants
       
Female      7  14.9%      10  13.7%      11  15.1%      28  14.5% 
Male      40  85.1%      63  86.3%      62  84.9%      165  85.5% 


  Outcome Measures

1.  Primary:   Phase II: Treatment Compliance (Number of Compliant Patients)   [ Time Frame: Randomization to 12 weeks ]

Measure Type Primary
Measure Title Phase II: Treatment Compliance (Number of Compliant Patients)
Measure Description Patients completing at least 19 out of 24 ALTENS therapy sessions were categorized as compliant. Fleming’s two-stage was used, assuming a successful target compliance rate of 80%, statistical power of 0.87, and a type I error rate of 0.13. If fewer than 9 of the first 13 patients were compliant, then treatment delivery will be deemed not feasible. If there were between 9-12 compliant patients, the second stage analysis would be required to determine feasibility of treatment delivery. If all 13 patients are compliant, treatment delivery will immediately be deemed feasible. The second stage analysis required at least 31 compliant out of 39 overall patients for the treatment delivery to be deemed feasible.
Time Frame Randomization to 12 weeks  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Eligible patients starting protocol treatment

Reporting Groups
  Description
ALTENS: Phase II Acupuncture-like transcutaneous electrical nerve stimulation (ALTENS) twice weekly for 12 weeks via a Codetron unit

Measured Values
   ALTENS: Phase II 
Participants Analyzed   47 
Phase II: Treatment Compliance (Number of Compliant Patients) 
[Units: Participants]
Count of Participants
 
First Stage   
Participants Analyzed   13 
First Stage   12 
Second Stage (Overall)   
Participants Analyzed   47 
Second Stage (Overall)   44 

No statistical analysis provided for Phase II: Treatment Compliance (Number of Compliant Patients)



2.  Primary:   Phase III: Change From Baseline in Overall Xerostomia Burden at 9 Months   [ Time Frame: Baseline (randomization) and 9 months ]

Measure Type Primary
Measure Title Phase III: Change From Baseline in Overall Xerostomia Burden at 9 Months
Measure Description Xerostomia burden is measured by the University of Michigan Xerostomia Related Quality of Life Scale (XeQOLS). The XeQOLS is a validated patient-reported 15-item assessment scale with 4 domains: physical functioning,pain/discomfort, personal/psychologic functioning, and social functioning.The score is the average of all responses of all domains and can range from 0 to 4, with higher scores indicating increased xerostomia burden. Change in xerostomia burden is calculated by subtracting the baseline score from the 9-month score such that a negative change indicates an improvement of the xerostomia burden.
Time Frame Baseline (randomization) and 9 months  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Eligible randomized patients with both baseline and 9 month XeQOLS scores

Reporting Groups
  Description
Pilocarpine: Phase III 5mg pilocarpine by mouth 3 times a day for 12 weeks
ALTENS: Phase III Acupuncture-like transcutaneous electrical nerve stimulation (ALTENS) twice weekly for 12 weeks via a Codetron unit

Measured Values
   Pilocarpine: Phase III   ALTENS: Phase III 
Participants Analyzed   43   53 
Phase III: Change From Baseline in Overall Xerostomia Burden at 9 Months 
[Units: Units on a scale]
Median (Inter-Quartile Range)
 -0.27 
 (-1.06 to 0) 
 -0.53 
 (-0.87 to -0.2) 


Statistical Analysis 1 for Phase III: Change From Baseline in Overall Xerostomia Burden at 9 Months
Groups [1] All groups
Statistical Test Type [2] Superiority
Statistical Method [3] Wilcoxon (Mann-Whitney)
P Value [4] 0.45
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  An effect size of 0.50 was chosen for sample size calculation. On the basis of a 2-sided t test with alpha= 0.05 and 1 interim analysis, 130 patients were required for 80% statistical power. Adjustment by 10% for loss to follow-up and retrospective ineligibility of recruited study participants yielded a sample size of 144 patients. Actual power given only 96 patients was 68.6%
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.



3.  Secondary:   Phase II: Pecentage of Patients With Beneficial Treatment Response   [ Time Frame: Pre-treatment and 6 months from registration ]

Measure Type Secondary
Measure Title Phase II: Pecentage of Patients With Beneficial Treatment Response
Measure Description This secondary objective was to evaluate the effect of ALTENS treatment on overall radiation-induced xerostomia burden by looking at treatment response. Treatment response was determined by a reduction of at least 20% from baseline to 6 months in the University of Michigan Xerostomia Related Quality of Life Scale (XeQOLS). The XeQOLS is a validated patient-reported 15-item assessment scale with 4 domains: physical functioning,pain/discomfort, personal/psychologic functioning, and social functioning.The score is the average of all responses of all domains and can range from 0 to 4. Higher scores indicate increased xerostomia burden. This scale has high reproducibility and sensitivity. For the first and second stage analyses, 4 and 10 patients, respectively, must respond to treatment in order to proceed to the phase III component.
Time Frame Pre-treatment and 6 months from registration  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Eligible patients who started treatment and have both baseline and 6-month XeQOLS scores

Reporting Groups
  Description
ALTENS: Phase II Acupuncture-like transcutaneous electrical nerve stimulation (ALTENS) twice weekly for 12 weeks via a Codetron unit

Measured Values
   ALTENS: Phase II 
Participants Analyzed   35 
Phase II: Pecentage of Patients With Beneficial Treatment Response 
[Units: Percentage of participants]
Number (95% Confidence Interval)
 85.7 
 (84.9 to 86.5) 

No statistical analysis provided for Phase II: Pecentage of Patients With Beneficial Treatment Response



4.  Secondary:   Change From Baseline in Overall Xerostomia Burden at 4, 6, and 15 Months (Phase III)   [ Time Frame: Baseline, 4, 6, and 15 months from randomization ]

Measure Type Secondary
Measure Title Change From Baseline in Overall Xerostomia Burden at 4, 6, and 15 Months (Phase III)
Measure Description Xerostomia burden is measured by the University of Michigan Xerostomia Related Quality of Life Scale (XeQOLS). The XeQOLS is a validated patient-reported 15-item assessment scale with 4 domains: physical functioning,pain/discomfort, personal/psychologic functioning, and social functioning.The score is the average of all responses of all domains and can range from 0 to 4, with higher scores indicating increased xerostomia burden. Change in xerostomia burden is calculated by subtracting the baseline score from the 9-month score such that a negative change indicates an improvement of the xerostomia burden.
Time Frame Baseline, 4, 6, and 15 months from randomization  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Eligible patients with both baseline and respective follow-up (4,6,15 months) XeQOLS scores.

Reporting Groups
  Description
Pilocarpine: Phase III 5mg pilocarpine by mouth 3 times a day for 12 weeks
ALTENS: Phase III Acupuncture-like transcutaneous electrical nerve stimulation (ALTENS) twice weekly for 12 weeks via a Codetron unit

Measured Values
   Pilocarpine: Phase III   ALTENS: Phase III 
Participants Analyzed   67   63 
Change From Baseline in Overall Xerostomia Burden at 4, 6, and 15 Months (Phase III) 
[Units: Units on a scale]
Median (Inter-Quartile Range)
   
4 months     
Participants Analyzed   67   52 
4 months   -0.27 
 (-0.6 to 0) 
 -0.47 
 (-0.8 to -0.13) 
6 months     
Participants Analyzed   45   47 
6 months   -0.33 
 (-0.73 to -0.2) 
 -0.4 
 (-0.87 to -0.14) 
15 months     
Participants Analyzed   67   47 
15 months   -0.47 
 (-0.87 to -0.07) 
 -0.6 
 (-1 to -0.2) 


Statistical Analysis 1 for Change From Baseline in Overall Xerostomia Burden at 4, 6, and 15 Months (Phase III)
Groups [1] All groups
Statistical Test Type [2] Superiority
Statistical Method [3] Wilcoxon (Mann-Whitney)
P Value [4] 0.11
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Two-sided test of values at 4 months.

Statistical Analysis 2 for Change From Baseline in Overall Xerostomia Burden at 4, 6, and 15 Months (Phase III)
Groups [1] All groups
Statistical Test Type [2] Superiority
Statistical Method [3] Wilcoxon (Mann-Whitney)
P Value [4] 0.31
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Two-sided test of values at 6 months.

Statistical Analysis 3 for Change From Baseline in Overall Xerostomia Burden at 4, 6, and 15 Months (Phase III)
Groups [1] All groups
Statistical Test Type [2] Superiority
Statistical Method [3] Wilcoxon (Mann-Whitney)
P Value [4] 0.21
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Two-sided test of values at 15 months.



5.  Secondary:   Change From Baseline in Symptom Burden at 4, 6, 9 and 15 Months (Phase III)   [ Time Frame: Baseline, 4, 6, 9 and 15 months from randomization ]

Measure Type Secondary
Measure Title Change From Baseline in Symptom Burden at 4, 6, 9 and 15 Months (Phase III)
Measure Description Symptom burden is measured by the University of Michigan Xerostomia Related Quality of Life Scale (XeQOLS). The XeQOLS is a validated patient-reported 15-item assessment scale with 4 domains: physical functioning,pain/discomfort, personal/psychologic functioning, and social functioning. The domain score is the average of all responses on a given domain and can range from 0 to 4, with higher scores indicating increased symptom burden. Change in symptom burden is calculated by subtracting the baseline score from the 9-month score such that a negative change indicates an improvement of the symptom burden.
Time Frame Baseline, 4, 6, 9 and 15 months from randomization  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Eligible patients with both baseline and respective follow-up (4,6, 9,15 months) XeQOLS scores.

Reporting Groups
  Description
Pilocarpine: Phase III 5mg pilocarpine by mouth 3 times a day for 12 weeks
ALTENS: Phase III Acupuncture-like transcutaneous electrical nerve stimulation (ALTENS) twice weekly for 12 weeks via a Codetron unit

Measured Values
   Pilocarpine: Phase III   ALTENS: Phase III 
Participants Analyzed   67   63 
Change From Baseline in Symptom Burden at 4, 6, 9 and 15 Months (Phase III) 
[Units: Units on a scale]
Median (Inter-Quartile Range)
   
4-month Physical Functioning     
Participants Analyzed   43   52 
4-month Physical Functioning   -0.5 
 (-0.75 to 0) 
 -0.5 
 (-0.75 to 0) 
4-month Pain/Discomfort     
Participants Analyzed   43   52 
4-month Pain/Discomfort   -0.25 
 (-0.75 to 0) 
 -0.375 
 (-1 to 0.125) 
4-month Personal/Psychological Functioning     
Participants Analyzed   43   52 
4-month Personal/Psychological Functioning   -0.25 
 (-0.5 to 0.25) 
 -0.5 
 (-0.875 to -0.125) 
4-month Social Functioning     
Participants Analyzed   43   52 
4-month Social Functioning   0 
 (-0.67 to 0.33) 
 -0.33 
 (-0.835 to 0) 
6-month Physical Functioning     
Participants Analyzed   45   47 
6-month Physical Functioning   -0.5 
 (-1 to 0) 
 -0.5 
 (-1 to 0) 
6-month Pain/Discomfort     
Participants Analyzed   45   47 
6-month Pain/Discomfort   -0.25 
 (-0.5 to 0) 
 -0.5 
 (-1 to 0) 
6-month Personal/Psychological Functioning     
Participants Analyzed   45   47 
6-month Personal/Psychological Functioning   -0.25 
 (-0.75 to 0) 
 -0.5 
 (-1 to -0.25) 
6-month Social Functioning     
Participants Analyzed   45   47 
6-month Social Functioning   -0.33 
 (-0.67 to 0.66) 
 -0.33 
 (-0.67 to 0) 
9-month Physical Functioning     
Participants Analyzed   43   53 
9-month Physical Functioning   -0.5 
 (-1.25 to 0) 
 -0.5 
 (-1 to -0.25) 
9-month Pain/Discomfort     
Participants Analyzed   43   53 
9-month Pain/Discomfort   -0.25 
 (-0.5 to 0) 
 -0.5 
 (-1 to 0) 
9-month Personal/Psychological Functioning     
Participants Analyzed   43   53 
9-month Personal/Psychological Functioning   -0.5 
 (-1 to 0.25) 
 -0.75 
 (-1 to -0.25) 
9-month Social Functioning     
Participants Analyzed   43   53 
9-month Social Functioning   -0.66 
 (-1 to 0.33) 
 -0.33 
 (-0.67 to 0) 
15-month Physical Functioning     
Participants Analyzed   43   47 
15-month Physical Functioning   -0.5 
 (-1 to 0) 
 -0.75 
 (-1.25 to -0.25) 
15-month Pain/Discomfort     
Participants Analyzed   43   47 
15-month Pain/Discomfort   -0.5 
 (-1 to 0) 
 -0.5 
 (-1 to 0) 
15-month Personal/Psychological Functioning     
Participants Analyzed   43   47 
15-month Personal/Psychological Functioning   -0.5 
 (-1 to 0) 
 -0.75 
 (-1.25 to -0.25) 
15-month Social Functioning     
Participants Analyzed   43   47 
15-month Social Functioning   0 
 (-1 to 0.33) 
 -0.33 
 (-0.67 to 0) 


Statistical Analysis 1 for Change From Baseline in Symptom Burden at 4, 6, 9 and 15 Months (Phase III)
Groups [1] All groups
Statistical Test Type [2] Superiority
Statistical Method [3] Wilcoxon (Mann-Whitney)
P Value [4] 0.35
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  4-month Physical Functioning score; two-sided test, significance level 0.05

Statistical Analysis 2 for Change From Baseline in Symptom Burden at 4, 6, 9 and 15 Months (Phase III)
Groups [1] All groups
Statistical Test Type [2] Superiority
Statistical Method [3] Wilcoxon (Mann-Whitney)
P Value [4] 0.78
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  4 months Pain/Discomfort score; two-sided test, significance level 0.05

Statistical Analysis 3 for Change From Baseline in Symptom Burden at 4, 6, 9 and 15 Months (Phase III)
Groups [1] All groups
Statistical Test Type [2] Superiority
Statistical Method [3] Wilcoxon (Mann-Whitney)
P Value [4] 0.12
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  4 months Personal/Psychological Functioning score; two-sided test, significance level 0.05

Statistical Analysis 4 for Change From Baseline in Symptom Burden at 4, 6, 9 and 15 Months (Phase III)
Groups [1] All groups
Statistical Test Type [2] Superiority
Statistical Method [3] Wilcoxon (Mann-Whitney)
P Value [4] 0.28
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  4-month Social Functioning score; two-sided test, significance level 0.05

Statistical Analysis 5 for Change From Baseline in Symptom Burden at 4, 6, 9 and 15 Months (Phase III)
Groups [1] All groups
Statistical Test Type [2] Superiority
Statistical Method [3] Wilcoxon (Mann-Whitney)
P Value [4] 0.98
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  6-month Physical Functioning score; two-sided test, significance level 0.05

Statistical Analysis 6 for Change From Baseline in Symptom Burden at 4, 6, 9 and 15 Months (Phase III)
Groups [1] All groups
Statistical Test Type [2] Superiority
Statistical Method [3] Wilcoxon (Mann-Whitney)
P Value [4] 0.28
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  6-month Pain/Discomfort score; two-sided test, significance level 0.05

Statistical Analysis 7 for Change From Baseline in Symptom Burden at 4, 6, 9 and 15 Months (Phase III)
Groups [1] All groups
Statistical Test Type [2] Superiority
Statistical Method [3] Wilcoxon (Mann-Whitney)
P Value [4] 0.13
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  6-month Personal/Psychological Functioning score; two-sided test, significance level 0.05

Statistical Analysis 8 for Change From Baseline in Symptom Burden at 4, 6, 9 and 15 Months (Phase III)
Groups [1] All groups
Statistical Test Type [2] Superiority
Statistical Method [3] Wilcoxon (Mann-Whitney)
P Value [4] 0.58
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  6-month Social Functioning score; two-sided test, significance level 0.05

Statistical Analysis 9 for Change From Baseline in Symptom Burden at 4, 6, 9 and 15 Months (Phase III)
Groups [1] All groups
Statistical Test Type [2] Superiority
Statistical Method [3] Wilcoxon (Mann-Whitney)
P Value [4] 0.88
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  9-month Physical Functioning score; two-sided test, significance level 0.05

Statistical Analysis 10 for Change From Baseline in Symptom Burden at 4, 6, 9 and 15 Months (Phase III)
Groups [1] All groups
Statistical Test Type [2] Superiority
Statistical Method [3] Wilcoxon (Mann-Whitney)
P Value [4] 0.09
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  9-month Pain/Discomfort score; two-sided test, significance level 0.05

Statistical Analysis 11 for Change From Baseline in Symptom Burden at 4, 6, 9 and 15 Months (Phase III)
Groups [1] All groups
Statistical Test Type [2] Superiority
Statistical Method [3] Wilcoxon (Mann-Whitney)
P Value [4] 0.49
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  9-month Personal/Psychological Functioning score; two-sided test, significance level 0.05

Statistical Analysis 12 for Change From Baseline in Symptom Burden at 4, 6, 9 and 15 Months (Phase III)
Groups [1] All groups
Statistical Test Type [2] Superiority
Statistical Method [3] Wilcoxon (Mann-Whitney)
P Value [4] 0.45
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  9-month Social Functioning score; two-sided test, significance level 0.05

Statistical Analysis 13 for Change From Baseline in Symptom Burden at 4, 6, 9 and 15 Months (Phase III)
Groups [1] All groups
Statistical Test Type [2] Superiority
Statistical Method [3] Wilcoxon (Mann-Whitney)
P Value [4] 0.45
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  15-month Physical Functioning; two-sided test, significance level 0.05

Statistical Analysis 14 for Change From Baseline in Symptom Burden at 4, 6, 9 and 15 Months (Phase III)
Groups [1] All groups
Statistical Test Type [2] Superiority
Statistical Method [3] Wilcoxon (Mann-Whitney)
P Value [4] 0.30
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  15-month Pain/Discomfort; two-sided test, significance level 0.05

Statistical Analysis 15 for Change From Baseline in Symptom Burden at 4, 6, 9 and 15 Months (Phase III)
Groups [1] All groups
Statistical Test Type [2] Superiority
Statistical Method [3] Wilcoxon (Mann-Whitney)
P Value [4] 0.48
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  15-month Personal/Psychological Functioning; two-sided test, significance level 0.05

Statistical Analysis 16 for Change From Baseline in Symptom Burden at 4, 6, 9 and 15 Months (Phase III)
Groups [1] All groups
Statistical Test Type [2] Superiority
Statistical Method [3] Wilcoxon (Mann-Whitney)
P Value [4] 0.68
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  15-month Social Functioning; two-sided test, significance level 0.05



6.  Secondary:   Change From Baseline in Stimulated Whole Salivary Production (WSP) at 4, 6, 9 and 15 Months (Phase III)   [ Time Frame: Baseline, 4, 6, 9 and 15 months from randomization ]

Measure Type Secondary
Measure Title Change From Baseline in Stimulated Whole Salivary Production (WSP) at 4, 6, 9 and 15 Months (Phase III)
Measure Description Stimulated (citric acid primed) whole salivary production (WSP) was measured by expectoration weight, with one gram of saliva produced considered as one ml of saliva. WSP is expressed in ml/min calculated by dividing the measured weight or volume of WSP by five. Procedure: Patients refrain from eating, drinking, and smoking at least two hours prior to each measurement. Stimulation is elicited by asking patients to rinse 5 ml of 2% citric acid solution in the mouth for 15 seconds and then completely expectorating the citric acid. For each measurement, patients are asked to expectorate continuously into a pre-weighed dry plastic container over a 5-minute period without swallowing. The collected saliva with the plastic container will be weighed (total weight) immediately after each collection. The total weight minus the weight of the container is the weight or volume of whole saliva collected.
Time Frame Baseline, 4, 6, 9 and 15 months from randomization  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Eligible patients with both baseline and respective follow-up (4,6, 9,15 months) WSP measurements.

Reporting Groups
  Description
Pilocarpine: Phase III 5mg pilocarpine by mouth 3 times a day for 12 weeks
ALTENS: Phase III Acupuncture-like transcutaneous electrical nerve stimulation (ALTENS) twice weekly for 12 weeks via a Codetron unit

Measured Values
   Pilocarpine: Phase III   ALTENS: Phase III 
Participants Analyzed   73   73 
Change From Baseline in Stimulated Whole Salivary Production (WSP) at 4, 6, 9 and 15 Months (Phase III) 
[Units: Ml/min]
Median (Inter-Quartile Range)
   
4 months   0.03 
 (-0.12 to 1.4) 
 0.2 
 (-0.2 to 0.9) 
6 months   0.2 
 (-0.27 to 1.33) 
 0.40 
 (-0.3 to 1.07) 
9 months   0.99 
 (0 to 1.9) 
 0.60 
 (-0.17 to 1.44) 
15 months   0.3 
 (-0.3 to 1.7) 
 0.20 
 (-0.13 to 2) 


Statistical Analysis 1 for Change From Baseline in Stimulated Whole Salivary Production (WSP) at 4, 6, 9 and 15 Months (Phase III)
Groups [1] All groups
Statistical Test Type [2] Superiority
Statistical Method [3] Wilcoxon (Mann-Whitney)
P Value [4] 0.97
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  4-month score; two-sided test, significance level 0.05

Statistical Analysis 2 for Change From Baseline in Stimulated Whole Salivary Production (WSP) at 4, 6, 9 and 15 Months (Phase III)
Groups [1] All groups
Statistical Test Type [2] Superiority
Statistical Method [3] Wilcoxon (Mann-Whitney)
P Value [4] 0.83
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  6-months; two-sided test, significance level 0.05

Statistical Analysis 3 for Change From Baseline in Stimulated Whole Salivary Production (WSP) at 4, 6, 9 and 15 Months (Phase III)
Groups [1] All groups
Statistical Test Type [2] Superiority
Statistical Method [3] Wilcoxon (Mann-Whitney)
P Value [4] 0.28
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  9-months; two-sided test, significance level 0.05

Statistical Analysis 4 for Change From Baseline in Stimulated Whole Salivary Production (WSP) at 4, 6, 9 and 15 Months (Phase III)
Groups [1] All groups
Statistical Test Type [2] Superiority
Statistical Method [3] Wilcoxon (Mann-Whitney)
P Value [4] 0.89
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  15-months; two-sided test, significance level 0.05



7.  Secondary:   Change From Baseline in Unstimulated Whole Salivary Production (WSP) at 4, 6, 9 and 15 Months (Phase III)   [ Time Frame: Pre-treatment to 4, 6, 9 and 15 months from randomization ]

Measure Type Secondary
Measure Title Change From Baseline in Unstimulated Whole Salivary Production (WSP) at 4, 6, 9 and 15 Months (Phase III)
Measure Description Basal whole salivary production (WSP) was measured by expectoration weight, with one gram of saliva produced considered as one ml of saliva. WSP is expressed in ml/min calculated by dividing the measured weight or volume of WSP by five. Procedure: Patients refrain from eating, drinking, and smoking at least two hours prior to each measurement. For each measurement, patients are asked to expectorate continuously into a pre-weighed dry plastic container over a 5-minute period without swallowing. The collected saliva with the plastic container will be weighed (total weight) immediately after each collection. The total weight minus the weight of the container is the weight or volume of whole saliva collected.
Time Frame Pre-treatment to 4, 6, 9 and 15 months from randomization  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Eligible randomized patients with both baseline and respective follow-up (4,6, 9,15 months) WSP measurements.

Reporting Groups
  Description
Pilocarpine: Phase III 5mg pilocarpine by mouth 3 times a day for 12 weeks
ALTENS: Phase III Acupuncture-like transcutaneous electrical nerve stimulation (ALTENS) twice weekly for 12 weeks via a Codetron unit

Measured Values
   Pilocarpine: Phase III   ALTENS: Phase III 
Participants Analyzed   73   73 
Change From Baseline in Unstimulated Whole Salivary Production (WSP) at 4, 6, 9 and 15 Months (Phase III) 
[Units: Ml/min]
Median (Inter-Quartile Range)
   
4 months     
Participants Analyzed   49   63 
4 months   0 
 (-0.3 to 0.29) 
 0 
 (-0.28 to 0.38) 
6 months     
Participants Analyzed   47   58 
6 months   0 
 (-0.3 to 0.7) 
 0.02 
 (-0.32 to 0.46) 
9 months     
Participants Analyzed   46   63 
9 months   0.056 
 (-0.1 to 0.9) 
 0.04 
 (-0.2 to 0.587) 
15 months     
Participants Analyzed   49   57 
15 months   0.13 
 (0 to 0.9) 
 0.192 
 (-0.2 to 0.8) 


Statistical Analysis 1 for Change From Baseline in Unstimulated Whole Salivary Production (WSP) at 4, 6, 9 and 15 Months (Phase III)
Groups [1] All groups
Statistical Test Type [2] Superiority
Statistical Method [3] Wilcoxon (Mann-Whitney)
P Value [4] 0.54
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  4-months; two-sided test, significance level 0.05

Statistical Analysis 2 for Change From Baseline in Unstimulated Whole Salivary Production (WSP) at 4, 6, 9 and 15 Months (Phase III)
Groups [1] All groups
Statistical Test Type [2] Superiority
Statistical Method [3] Wilcoxon (Mann-Whitney)
P Value [4] 0.99
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  6-months; two-sided test, significance level 0.05

Statistical Analysis 3 for Change From Baseline in Unstimulated Whole Salivary Production (WSP) at 4, 6, 9 and 15 Months (Phase III)
Groups [1] All groups
Statistical Test Type [2] Superiority
Statistical Method [3] Wilcoxon (Mann-Whitney)
P Value [4] 0.56
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  6-months; two-sided test, significance level 0.05

Statistical Analysis 4 for Change From Baseline in Unstimulated Whole Salivary Production (WSP) at 4, 6, 9 and 15 Months (Phase III)
Groups [1] All groups
Statistical Test Type [2] Superiority
Statistical Method [3] Wilcoxon (Mann-Whitney)
P Value [4] 0.58
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  6-months; two-sided test, significance level 0.05



8.  Secondary:   Quality of Life (QOL) as Measured by the University of Washington Head and Neck Questionnaire (UWHNSS) Phase III   [ Time Frame: Baseline and 9 months from randomization. ]

Measure Type Secondary
Measure Title Quality of Life (QOL) as Measured by the University of Washington Head and Neck Questionnaire (UWHNSS) Phase III
Measure Description The UWHNSS includes ten categories—pain, disfigurement, activity, recreation/entertainment, employment, eating, saliva, taste, speech, mucus/phlegm. Patient scores on the UWHNSS range from 0 to 100 with higher scores indicating declining quality of life. Change in total score was calculated by subtracting baseline from follow-up , thus a positive change score indicates a worsening while a negative change score indicates an improvement.
Time Frame Baseline and 9 months from randomization.  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Eligible randomized patients with both baseline and 9-month UWHNSS total scores.

Reporting Groups
  Description
Pilocarpine: Phase III 5mg pilocarpine by mouth 3 times a day for 12 weeks
ALTENS: Phase III Acupuncture-like transcutaneous electrical nerve stimulation (ALTENS) twice weekly for 12 weeks via a Codetron unit

Measured Values
   Pilocarpine: Phase III   ALTENS: Phase III 
Participants Analyzed   43   51 
Quality of Life (QOL) as Measured by the University of Washington Head and Neck Questionnaire (UWHNSS) Phase III 
[Units: Units on a scale]
Median (Inter-Quartile Range)
 -3.64 
 (-9.09 to 1.82) 
 -7.27 
 (-12.73 to -1.81) 


Statistical Analysis 1 for Quality of Life (QOL) as Measured by the University of Washington Head and Neck Questionnaire (UWHNSS) Phase III
Groups [1] All groups
Statistical Test Type [2] Superiority
Statistical Method [3] t-test, 2 sided
P Value [4] 0.14
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Two-sided test, significance level 0.05




  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


  More Information

Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Wendy Seiferheld, M.S.
Organization: NRG Oncology
e-mail: seiferheldw@nrgoncology.org


Publications of Results:

Responsible Party: Radiation Therapy Oncology Group
ClinicalTrials.gov Identifier: NCT00656513     History of Changes
Other Study ID Numbers: RTOG-0537
CDR0000592644
First Submitted: April 10, 2008
First Posted: April 11, 2008
Results First Submitted: June 22, 2017
Results First Posted: August 21, 2017
Last Update Posted: August 21, 2017