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The Efficacy of Low Dose Naltrexone Therapy in Children With Crohn's Disease (LDN-Ped)

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ClinicalTrials.gov Identifier: NCT00715117
Recruitment Status : Completed
First Posted : July 15, 2008
Results First Posted : May 30, 2013
Last Update Posted : September 6, 2018
Sponsor:
Information provided by (Responsible Party):
Milton S. Hershey Medical Center

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Crohn's Disease
Interventions Drug: Naltrexone
Other: Placebo, sugar pill
Enrollment 14
Recruitment Details 14 subjects were enrolled in this pilot trial and 2 were screen failures and not randomized or treated
Pre-assignment Details The 2 subjects who were screen failures had PCDAI scores less than 30.
Arm/Group Title A: Placebo Then Naltrexone B: Naltrexone Then Naltrexone
Hide Arm/Group Description Subjects will receive placebo for for the first 8weeks then be crossed over to active drug naltrexone for the last 8 weeks Naltrexone 0.1 mg/kg (not to exceed 4.5mg) once a day for 8 weeks followed by the same treatment for an additional 8 weeks
Period Title: Overall Study
Started 6 6
Completion fo 8 Week Study 6 6
Completed 6 5 [1]
Not Completed 0 1
Reason Not Completed
Crohn's flare and rescue with steroids             0             1
[1]
One subject flared and was rescued with steroids
Arm/Group Title A: Placebo Control Group B: Naltrexone, Active Drug Group Total
Hide Arm/Group Description Subjects will receive placebo for for the first 8weeks then be crossed over to active drug for the last 8 weeks Naltrexone 0.1 mg/kg (not to exceed 4.5mg) once a day for 16 weeks Total of all reporting groups
Overall Number of Baseline Participants 6 6 12
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 6 participants 12 participants
<=18 years
6
 100.0%
6
 100.0%
12
 100.0%
Between 18 and 65 years
0
   0.0%
0
   0.0%
0
   0.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 6 participants 6 participants 12 participants
12.2  (3.31) 13  (3.22) 12.5  (3.2)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 6 participants 12 participants
Female
2
  33.3%
5
  83.3%
7
  58.3%
Male
4
  66.7%
1
  16.7%
5
  41.7%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 6 participants 12 participants
Female
2
  33.3%
5
  83.3%
7
  58.3%
Male
4
  66.7%
1
  16.7%
5
  41.7%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 6 participants 6 participants 12 participants
6 6 12
Pediatric Crohn's Disease Activity Index (PCDAI) score   [1] 
Mean (Full Range)
Unit of measure:  Score
Number Analyzed 6 participants 6 participants 12 participants
45
(35 to 52.5)
38.3
(30 to 57)
41.7
(30 to 57)
[1]
Measure Description: The PCDAI score is a number unit that is calculated from symptoms scores by the subject over a 7-day period prior to the visit, laboratory values, height & weight, and physical exam findings. A score of 10 and under denotes "remission". Mild disease (score of 11-30); moderate disease (score of 31-45), a severe disease (scores greater than 45. A decline of 10 points or more is considered "response to therapy". The score can range from 0 to >60 Patient must have a PCDAI score of equal or greater than 30 to qualify for this study (i.e., moderate to severe disease).
1.Primary Outcome
Title Number of Patients Reporting Side Effects
Hide Description Using adverse events and laboratory values Safety & toxicity were evaluated between those on placebo for 8 weeks and those on naltrexone for either 8 or 16 weeks.
Time Frame 8 weeks or 16 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The Fisher Exact Test was used to evaluate the number of side effects reported between placebo and naltrexone groups. The Student T-test was used to evaluate the differences between the mena values of laboratory tests.
Arm/Group Title Placebo Naltrexone
Hide Arm/Group Description:
These subjects received placebo for 8 weeks by mouth daily.
These subjects were treated with naltrexone at a dose 0.1 mg/kg not to exceed 4.5 mg po daily for either 8 or 16 weeks.
Overall Number of Participants Analyzed 6 12
Measure Type: Number
Unit of Measure: participants
Sleep disturbance 2 2
Unusal Dreams 0 2
Twitching 1 1
Headaches 1 0
Decreased appetite 1 0
Nausea 0 1
Hair loss 1 0
Fatigue 1 0
Flushed ears 0 1
Papules, rash 1 0
Double vision 0 1
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Naltrexone
Comments Sleep disturbance
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.0
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Naltrexone
Comments Unusual dreams
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.45
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Naltrexone
Comments Twitching
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.0
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Naltrexone
Comments Headaches
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.0
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, Naltrexone
Comments Decreased appetite
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.0
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, Naltrexone
Comments Nausea
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.0
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Placebo, Naltrexone
Comments Hair loss
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.0
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Placebo, Naltrexone
Comments Fatigue
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.0
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Placebo, Naltrexone
Comments Flushed ears
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.0
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Placebo, Naltrexone
Comments Papules, rash
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.0
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 11 Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Placebo, Naltrexone
Comments Double vision
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.0
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
2.Secondary Outcome
Title Pediatric Crohn's Disease Activity Index Score (PCDAI)
Hide Description

Secondary outcome was efficacy on clinical activity. Mean pretreatment PCDAI scores in patients had moderate to severe disease activity at baseline were compared between those who received placebo for 8 weeks and those who received active experimental drug, naltrexone.

The PCDAI score is a number unit that is calculated from symptoms scores by the subject over a 7-day period prior to the visit, laboratory values, height & weight, and physical exam findings. A score of 10 and under denotes "remission". Mild disease (score of 11-30); moderate disease (score of 31-45), a severe disease (scores greater than 45. A decline of 10 points or more is considered "response to therapy". The score can range from 0 to >60 Patient must have a PCDAI score of equal or greater than 30 to qualify for this study (i.e., moderate to severe disease).

Time Frame Pretreatment and 8 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The power calculations were performed using STPLAN version 4.1. The current investigation was designed as a pseudo-cross over study to increase the number of participants. In the proposed study, it was assumed that 80% would respond to naltrexone and that no more than 25% of the placebo.
Arm/Group Title All Participants Pretreament Placebo Naltrexone
Hide Arm/Group Description:
All participants prior to receiving placebo or naltrexone at week 0
Patients were treated with a placebo (sugar pill)for 8 weeks.
Includes all Naltrexone treated participants 8 weeks of treatment.
Overall Number of Participants Analyzed 12 6 12
Mean (Standard Error)
Unit of Measure: units on a scale
34.2  (3.3) 30  (4.9) 21.7  (3.9)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection All Participants Pretreament, Naltrexone
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.005
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Naltrexone
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.05
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
3.Secondary Outcome
Title Change in Quality of Life Scores From Baseline to After 8 Weeks of Naltrexone Therapy
Hide Description IMPACT III was a pediatric Crohn's specific quality of life survey used in this study. It examines five major categories influencing the quality of life in children with Crohn’s disease including bowel symptoms, systemic symptoms, emotional well-being, social well-being, and body image perception. The IMPACT-III uses 5-point Likert scale ranging from 1 to 5 for all answers. The outcome score ranges from 35 to 175, with higher scores suggesting better quality of life. So an increase in score denotes improved Quality of life.
Time Frame 16 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Baseline Week 16
Hide Arm/Group Description:
Quality of life values in all subjects at baseline before receiving placebo or naltrexone.
Quality of life survey values in all subjects determined at week 16 after all 12 participants had received naltrexone for either 8 or 16 weeks.
Overall Number of Participants Analyzed 12 12
Mean (Standard Error)
Unit of Measure: units on a scale
Bowel symptoms 20  (2.1) 23  (1.9)
Social well-being 40  (0.9) 45  (0.8)
Emotional Well-being 20  (1.6) 24  (1.5)
Systemic symtoms 9.8  (0.2) 10.1  (0.2)
Body image 10.2  (0.2) 10.3  (0.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Baseline, Week 16
Comments Bowel symptoms
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.05
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Baseline, Week 16
Comments Social well-being
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.035
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Baseline, Week 16
Comments Emotional well-being
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.05
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Baseline, Week 16
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.035
Comments Systemic symptoms
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Baseline, Week 16
Comments Body Image
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.05
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title A: Placebo Control Group B: Naltrexone, Active Drug Group
Hide Arm/Group Description Subjects will receive placebo for 8weeks Naltrexone 0.1 mg/kg (not to exceed 4.5mg) once a day for 8 or 16 weeks
All-Cause Mortality
A: Placebo Control Group B: Naltrexone, Active Drug Group
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
A: Placebo Control Group B: Naltrexone, Active Drug Group
Affected / at Risk (%) Affected / at Risk (%)
Total   0/6 (0.00%)   0/12 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
A: Placebo Control Group B: Naltrexone, Active Drug Group
Affected / at Risk (%) Affected / at Risk (%)
Total   5/6 (83.33%)   4/12 (33.33%) 
Eye disorders     
Double vision  0/6 (0.00%)  1/12 (8.33%) 
Gastrointestinal disorders     
Nausea  0/6 (0.00%)  1/12 (8.33%) 
General disorders     
Fatigue  1/6 (16.67%)  0/12 (0.00%) 
Metabolism and nutrition disorders     
Decreased appetite  1/6 (16.67%)  0/12 (0.00%) 
Nervous system disorders     
Twitching  1/6 (16.67%)  1/12 (8.33%) 
Headaches  1/6 (16.67%)  0/12 (0.00%) 
Psychiatric disorders     
Sleep disturbance  2/6 (33.33%)  2/12 (16.67%) 
Unusual dreams  0/6 (0.00%)  2/12 (16.67%) 
Skin and subcutaneous tissue disorders     
Hair loss  1/6 (16.67%)  0/12 (0.00%) 
Papules, rash  1/6 (16.67%)  0/12 (0.00%) 
Vascular disorders     
Flushed ears  0/6 (0.00%)  1/12 (8.33%) 
This was a pseudo-crossover trial where 6 subjects received placebo for 8 wks then were crossed over to active drug for 8 wks to increase the N treated with active drug. A smaller cohort of subjects on placebo were for safety & toxicity comparison.
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.
No restrictions by the sponsor. The PI may disclose results after the manuscript has been published.
Results Point of Contact
Name/Title: Jill P Smith, MD Professor Emeritus of medicine
Organization: Pennsylvania State University
Phone: 717-531-3694
Responsible Party: Milton S. Hershey Medical Center
ClinicalTrials.gov Identifier: NCT00715117     History of Changes
Other Study ID Numbers: PSU-IRB-27793
First Submitted: July 14, 2008
First Posted: July 15, 2008
Results First Submitted: August 4, 2011
Results First Posted: May 30, 2013
Last Update Posted: September 6, 2018