Somatropin Treatment to Final Height in Turner Syndrome (GDCT)

This study has been completed.
Sponsor:
Information provided by:
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT00191113
First received: September 12, 2005
Last updated: December 13, 2009
Last verified: December 2009
Results First Received: December 1, 2008  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Turner Syndrome
Interventions: Drug: Somatropin
Drug: Ethinyl estradiol
Drug: Medroxyprogesterone acetate

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Addenda 1, 2, and 3 are not sequential, and they differ in eligibility criteria. Depending on individual eligibility and choices made, a patient might have participated in none, 1, 2, or all 3 of these addenda.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Addendum 1: provided option of Humatrope treatment to patients who had been randomized to control in Core Study. Addendum 2: extended period of follow-up for 5 years after discontinuation from Core Study. Addendum 3: evaluated possible genomic imprinting effects (published: Hamelin et al. 2006).

Reporting Groups
  Description
As-Randomized Control Control arm; untreated with Humatrope. Ethinyl estradiol (escalating doses to 20 mcg daily) after age 13, and medroxyprogesterone acetate (10 mg tablets ten days monthly) after age 15. Subject continues until Core study completion criteria are met (protocol final height).
As-Randomized Humatrope Humatrope (0.05 mg/kg/dose) by subcutaneous injection 6 times per week. Ethinyl estradiol (escalating doses to 20 mcg daily) after age 13, and medroxyprogesterone acetate (10 mg tablets ten days monthly) after age 15. Subject continues until Core study completion criteria are met (protocol final height).

Participant Flow for 4 periods

Period 1:   Core Study
    As-Randomized Control     As-Randomized Humatrope  
STARTED     78     76  
COMPLETED     43     61  
NOT COMPLETED     35     15  
Withdrawal by Subject                 25                 9  
Protocol Violation                 6                 2  
Lost to Follow-up                 3                 0  
Adverse Event                 0                 2  
Lack of Efficacy                 0                 2  
Death                 1                 0  

Period 2:   Addendum 1
    As-Randomized Control     As-Randomized Humatrope  
STARTED     2     0 [1]
COMPLETED     2     0 [1]
NOT COMPLETED     0     0  
[1] Not Applicable -- only Control patients were eligible for Addendum 1

Period 3:   Addendum 2
    As-Randomized Control     As-Randomized Humatrope  
STARTED     28     48  
COMPLETED     18     31  
NOT COMPLETED     10     17  

Period 4:   Addendum 3
    As-Randomized Control     As-Randomized Humatrope  
STARTED     20     37  
COMPLETED     20     37  
NOT COMPLETED     0     0  



  Baseline Characteristics
  Hide 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.
No text entered.

Reporting Groups
  Description
As-Randomized Control Control arm; untreated with Humatrope. Ethinyl estradiol (escalating doses to 20 mcg daily) after age 13, and medroxyprogesterone acetate (10 mg tablets ten days monthly) after age 15. Subject continues until Core study completion criteria are met (protocol final height).
As-Randomized Humatrope Humatrope (0.05 mg/kg/dose) by subcutaneous injection 6 times per week. Ethinyl estradiol (escalating doses to 20 mcg daily) after age 13, and medroxyprogesterone acetate (10 mg tablets ten days monthly) after age 15. Subject continues until Core study completion criteria are met (protocol final height).
Total Total of all reporting groups

Baseline Measures
    As-Randomized Control     As-Randomized Humatrope     Total  
Number of Participants  
[units: participants]
  78     76     154  
Age  
[units: years]
Mean ± Standard Deviation
  10.46  ± 1.77     10.36  ± 1.80     10.41  ± 1.78  
Gender  
[units: participants]
     
Female     78     76     154  
Male     0     0     0  
Region of Enrollment  
[units: participants]
     
Canada     78     76     154  
Karyotype  
[units: participants]
     
45,X     48     45     93  
45,X/46,XXqi     6     2     8  
45,X/46,XXr     1     2     3  
45,X/46,XX     3     3     6  
46,XXqi     2     6     8  
45,X/47,XXX     1     2     3  
46,XXp     1     0     1  
45,X/46,XXp     1     1     2  
45,X/46,XX/47,XXX     0     0     0  
46,XXr     0     0     0  
Other     15     15     30  
Race/Ethnicity  
[units: participants]
     
American Indian or Alaska Native     1     1     2  
Asian     7     6     13  
Native Hawaiian or Other Pacific Islander     0     0     0  
Black or African American     1     0     1  
White     54     66     120  
Hispanic     0     2     2  
Other     4     0     4  
Unknown     11     1     12  
Bone Age [1]
[units: years]
Mean ± Standard Deviation
  8.57  ± 1.51     8.79  ± 1.42     8.69  ± 1.46  
Height  
[units: centimeters]
Mean ± Standard Deviation
  120.06  ± 8.26     119.84  ± 8.45     119.96  ± 8.33  
Height Standard Deviation Score (SDS) [Lyon] [2]
[units: Standard Deviation Score (SDS)]
Mean ± Standard Deviation
  -0.13  ± 0.86     -0.10  ± 0.88     -0.11  ± 0.87  
Height Standard Deviation Score (SDS) [National Center for Health Statistics (NCHS)] [3]
[units: Standard Deviation Score (SDS)]
Mean ± Standard Deviation
  -3.25  ± 0.82     -3.21  ± 0.82     -3.23  ± 0.82  
[1] Bone age was determined by the Greulich-Pyle method.
[2] SDS report the number of standard deviations from the mean for age and sex for an individual measurement (normal range: -2 to +2 SDS). Height SDS [Lyon] uses the Turner syndrome reference height values for age (Lyon AJ et al. 1985) as the population mean and standard deviation. Height SDS is derived by subtracting the population mean from individual’s height value and then dividing that difference by the population standard deviation. Since the data reported by Lyon AJ et al represent a Turner syndrome reference standard, values for patients with Turner syndrome are centered around zero.
[3] SDS report the number of standard deviations from the mean for age and sex for an individual measurement (normal range: -2 to +2 SDS). Height SDS [NCHS] uses the NCHS US general female population reference height values for age (Kuczmarski RJ et al. 2000) as the population mean and standard deviation. Calculation of Height SDS is provided in Height SDS [Lyon] description (baseline). Since data reported by Kuczmarski RJ et al provides US general female population standards, values of Height SDS [NCHS] for untreated patients with Turner syndrome tend to be below zero e.g, -2.0 to -4.0 SDS.



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Height Standard Deviation Score (SDS) (National Center for Health Statistics [NCHS]), Change From Baseline to Last Measurement, As Randomized Population   [ Time Frame: Baseline, and end of 4-year addendum ]

2.  Primary:   Height Standard Deviation Score (SDS) (National Center for Health Statistics [NCHS]), Last Measurement After Attainment of Final Height   [ Time Frame: at completion of core study, or at end of 4-year addendum ]

3.  Secondary:   Height Standard Deviation Score (SDS) (National Center for Health Statistics [NCHS]), Change From Baseline, As-Treated Population   [ Time Frame: every 3 months during core study, and at start and end of 4-year addendum ]

4.  Secondary:   Height (Centimeters [cm])   [ Time Frame: every 3 months during core study, and at start and end of 4-year addendum ]

5.  Secondary:   Number of Participants With an Abnormal Pure Tone Audiometry, Audiologist Assessment   [ Time Frame: at completion of core study or beginning of addendum ]

6.  Secondary:   Number of Participants With Abnormal Speech Audiometry, Audiologist Assessment   [ Time Frame: at completion of core study or beginning of addendum ]

7.  Secondary:   Number of Participants With Abnormal Impedance Tympanometry, Audiologist Assessment   [ Time Frame: at completion of core study or beginning of addendum ]

8.  Secondary:   Number of Participants With Hearing Loss, Audiologist Assessment   [ Time Frame: at completion of core study or beginning of addendum ]

9.  Secondary:   Fasting Glucose, Change From Baseline   [ Time Frame: At core study baseline, and at end of 4-year addendum ]

10.  Secondary:   Maximum Fasting Glucose Value   [ Time Frame: At start and through end of 4-year addendum (up to an additional 2 years) ]

11.  Secondary:   Number of Participants With Any Abnormal Fasting Glucose Value   [ Time Frame: At start and through end of 4-year addendum ]

12.  Secondary:   Maximum Fasting Insulin Values   [ Time Frame: At start and through end of 4-year addendum (up to an additional 2 years) ]

13.  Secondary:   Number of Participants With Any Abnormal Fasting Insulin Value   [ Time Frame: At start and through end of 4-year addendum ]

14.  Secondary:   Minimum Fasting Glucose/Insulin Ratio Values   [ Time Frame: At start and through end of 4-year addendum (up to an additional 2 years) ]

15.  Secondary:   Number of Participants With Any Abnormal Fasting Glucose/Insulin Ratio Value   [ Time Frame: At start and through end of 4-year addendum ]

16.  Secondary:   Glycosylated Hemoglobin, Change From Baseline   [ Time Frame: At core study baseline, and at end of 4-year addendum ]

17.  Secondary:   Maximum Glycosylated Hemoglobin   [ Time Frame: At start and through end of 4-year addendum (up to an additional 2 years) ]

18.  Secondary:   Number of Participants With Any Abnormal Glycosylated Hemoglobin (HbA1c) Value   [ Time Frame: At start and through end of 4-year addendum ]


  Serious Adverse Events


  Other Adverse Events


  More Information
  Hide 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 Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.


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.  


Results Point of Contact:  
Name/Title: Chief Medical Officer
Organization: Eli Lilly and Company
phone: 1-800-545-5979


Publications of Results:
Other Publications:
Publications automatically indexed to this study:

Responsible Party: Chief Medical Officer, Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT00191113     History of Changes
Other Study ID Numbers: 817/4419, #817 B9R-CA-GDCT Core study, #4419 GDCT/1 Addenda
Study First Received: September 12, 2005
Results First Received: December 1, 2008
Last Updated: December 13, 2009
Health Authority: Canada: Health Canada
United States: Food and Drug Administration