Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 22 of 29 for:    "Turner Syndrome" | "Estrogens"

Somatropin Treatment to Final Height in Turner Syndrome (GDCT)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00191113
Recruitment Status : Completed
First Posted : September 19, 2005
Results First Posted : January 27, 2010
Last Update Posted : January 27, 2010
Sponsor:
Information provided by:
Eli Lilly and Company

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Turner Syndrome
Interventions Drug: Somatropin
Drug: Ethinyl estradiol
Drug: Medroxyprogesterone acetate
Enrollment 154
Recruitment Details 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 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).
Arm/Group Title As-Randomized Control As-Randomized Humatrope
Hide Arm/Group Description 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). 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).
Period Title: Core Study
Started 78 76
Completed 43 61
Not Completed 35 15
Reason Not Completed
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 Title: Addendum 1
Started 2 0 [1]
Completed 2 0 [1]
Not Completed 0 0
[1]
Not Applicable -- only Control patients were eligible for Addendum 1
Period Title: Addendum 2
Started 28 48
Completed 18 31
Not Completed 10 17
Period Title: Addendum 3
Started 20 37
Completed 20 37
Not Completed 0 0
Arm/Group Title As-Randomized Control As-Randomized Humatrope Total
Hide Arm/Group Description 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). 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 of all reporting groups
Overall Number of Baseline Participants 78 76 154
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 78 participants 76 participants 154 participants
10.46  (1.77) 10.36  (1.80) 10.41  (1.78)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 78 participants 76 participants 154 participants
Female
78
 100.0%
76
 100.0%
154
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Canada Number Analyzed 78 participants 76 participants 154 participants
78 76 154
Karyotype  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 78 participants 76 participants 154 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  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 78 participants 76 participants 154 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] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 78 participants 76 participants 154 participants
8.57  (1.51) 8.79  (1.42) 8.69  (1.46)
[1]
Measure Description: Bone age was determined by the Greulich-Pyle method.
Height  
Mean (Standard Deviation)
Unit of measure:  Centimeters
Number Analyzed 78 participants 76 participants 154 participants
120.06  (8.26) 119.84  (8.45) 119.96  (8.33)
Height Standard Deviation Score (SDS) [Lyon]   [1] 
Mean (Standard Deviation)
Unit of measure:  Standard Deviation Score (SDS)
Number Analyzed 78 participants 76 participants 154 participants
-0.13  (0.86) -0.10  (0.88) -0.11  (0.87)
[1]
Measure Description: 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.
Height Standard Deviation Score (SDS) [National Center for Health Statistics (NCHS)]   [1] 
Mean (Standard Deviation)
Unit of measure:  Standard Deviation Score (SDS)
Number Analyzed 78 participants 76 participants 154 participants
-3.25  (0.82) -3.21  (0.82) -3.23  (0.82)
[1]
Measure Description: 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.
1.Primary Outcome
Title Height Standard Deviation Score (SDS) (National Center for Health Statistics [NCHS]), Change From Baseline to Last Measurement, As Randomized Population
Hide Description Value analyzed is change from baseline to the most mature height measurement available. The terms Standard Deviation Score (SDS) and National Center for Health Statistics (NCHS) were defined in baseline characteristics. Greater height SDS values indicate greater height; positive values of change from baseline indicate increased height.
Time Frame Baseline, and end of 4-year addendum
Hide Outcome Measure Data
Hide Analysis Population Description
Population of all randomized patients. Intent to treat analysis with as-randomized treatment groups, at most mature measurement available.
Arm/Group Title As-Randomized Control As-Randomized Humatrope
Hide Arm/Group Description:
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).
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).
Overall Number of Participants Analyzed 78 76
Least Squares Mean (Standard Error)
Unit of Measure: Standard Deviation Score (SDS) [NCHS]
0.09  (0.07) 0.97  (0.07)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection As-Randomized Control, As-Randomized Humatrope
Comments This component of the primary analysis is inferential i.e. to ascertain definitively whether Humatrope treatment affects change in Height SDS (NCHS). Null hypothesis is no effect of Humatrope treatment.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments Model includes baseline height SDS, baseline age, treatment, and interactions. Age and interaction terms removed when not significant.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.9
Confidence Interval 95%
0.7 to 1.1
Estimation Comments Effect direction is "As-Randomized Humatrope" minus "As-Randomized Control"
2.Primary Outcome
Title Height Standard Deviation Score (SDS) (National Center for Health Statistics [NCHS]), Last Measurement After Attainment of Final Height
Hide Description 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.
Time Frame at completion of core study, or at end of 4-year addendum
Hide Outcome Measure Data
Hide Analysis Population Description
Population of patients for whom Final Height measurements are available. Efficacy analysis with as-treated treatment groups, at most mature measurement available at or after attainment of Final Height.
Arm/Group Title As-Treated No Growth Hormone As-Treated Growth Hormone
Hide Arm/Group Description:
Patients who never received growth hormone
Patients who received Humatrope or another brand of growth hormone
Overall Number of Participants Analyzed 48 82
Least Squares Mean (Standard Error)
Unit of Measure: Standard Deviation Score (SDS) [NCHS]
-3.30  (0.07) -2.25  (0.05)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection As-Treated No Growth Hormone, As-Treated Growth Hormone
Comments Estimation analysis of the magnitude of effect of treatment with growth hormone upon Final Height. Null hypothesis is no effect of growth hormone upon attained height standard deviation score (National Center for Health Statistics).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments Model includes baseline height SDS, baseline age, treatment, and interactions. Age and interactions terms removed when not significant.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 1.0
Confidence Interval 95%
0.9 to 1.2
Estimation Comments Effect direction is "As-Treated Growth Hormone" minus "As-Treated No Growth Hormone"
3.Secondary Outcome
Title Height Standard Deviation Score (SDS) (National Center for Health Statistics [NCHS]), Change From Baseline, As-Treated Population
Hide Description Value analyzed is change from baseline to the most mature height measurement available. The terms Standard Deviation Score (SDS) and National Center for Health Statistics (NCHS) were defined in baseline characteristics. Greater height SDS values indicate greater height; positive values of change from baseline indicate increased height.
Time Frame every 3 months during core study, and at start and end of 4-year addendum
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title As-Treated No Growth Hormone As-Treated Growth Humatrope
Hide Arm/Group Description:
Patients who never received growth hormone
Patients who received Humatrope or another brand of growth hormone
Overall Number of Participants Analyzed 48 82
Least Squares Mean (Standard Error)
Unit of Measure: Standard Deviation Score (SDS) [NCHS]
-0.09  (0.08) 0.99  (0.06)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection As-Treated No Growth Hormone, As-Treated Growth Humatrope
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 1.1
Confidence Interval 95%
0.9 to 1.3
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Height (Centimeters [cm])
Hide Description Most mature measurement available, at or after attainment of Final Height.
Time Frame every 3 months during core study, and at start and end of 4-year addendum
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title As-Treated No Growth Hormone As-Treated Growth Humatrope
Hide Arm/Group Description:
Patients who never received growth hormone
Patients who received Humatrope or another brand of growth hormone
Overall Number of Participants Analyzed 48 82
Least Squares Mean (Standard Error)
Unit of Measure: centimeters (cm)
141.63  (0.47) 148.52  (0.36)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection As-Treated No Growth Hormone, As-Treated Growth Humatrope
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 6.9
Confidence Interval 95%
5.7 to 8.1
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Number of Participants With an Abnormal Pure Tone Audiometry, Audiologist Assessment
Hide Description [Not Specified]
Time Frame at completion of core study or beginning of addendum
Hide Outcome Measure Data
Hide Analysis Population Description
All Randomized Patients with Hearing Examination
Arm/Group Title As-Treated No Growth Hormone As-Treated Growth Hormone
Hide Arm/Group Description:
Patients who never received growth hormone
Patients who received Humatrope or another brand of growth hormone
Overall Number of Participants Analyzed 19 53
Measure Type: Number
Unit of Measure: participants
10 29
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection As-Treated No Growth Hormone, As-Treated Growth Hormone
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.999
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
6.Secondary Outcome
Title Number of Participants With Abnormal Speech Audiometry, Audiologist Assessment
Hide Description [Not Specified]
Time Frame at completion of core study or beginning of addendum
Hide Outcome Measure Data
Hide Analysis Population Description
All Randomized Patients with Hearing Examination
Arm/Group Title As-Treated No Growth Hormone As-Treated Growth Hormone
Hide Arm/Group Description:
Patients who never received growth hormone
Patients who received Humatrope or another brand of growth hormone
Overall Number of Participants Analyzed 19 53
Measure Type: Number
Unit of Measure: participants
3 12
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection As-Treated No Growth Hormone, As-Treated Growth Hormone
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.744
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
7.Secondary Outcome
Title Number of Participants With Abnormal Impedance Tympanometry, Audiologist Assessment
Hide Description [Not Specified]
Time Frame at completion of core study or beginning of addendum
Hide Outcome Measure Data
Hide Analysis Population Description
All Randomized Patients with Hearing Examination
Arm/Group Title As-Treated No Growth Hormone As-Treated Growth Hormone
Hide Arm/Group Description:
Patients who never received growth hormone
Patients who received Humatrope or another brand of growth hormone
Overall Number of Participants Analyzed 19 53
Measure Type: Number
Unit of Measure: participants
2 18
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection As-Treated No Growth Hormone, As-Treated Growth Hormone
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.073
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
8.Secondary Outcome
Title Number of Participants With Hearing Loss, Audiologist Assessment
Hide Description Sensorineural Hearing Loss (SNHL)=air conduction threshold >20 dB HL and air-bone gap ≤10 dB HL; Conductive Hearing Loss (CHL)= air conduction threshold >20 dB HL, bone conduction threshold ≤20 dB HL and air-bone gap >10 dB HL; Mixed Hearing Loss (MHL) = evidence of SNHL as defined above and CHL as defined above, in the same ear; Unspecified Hearing Loss (UHL)= abnormal hearing with none of SNHL, CHL, or MHL present.
Time Frame at completion of core study or beginning of addendum
Hide Outcome Measure Data
Hide Analysis Population Description
All Randomized Patients with Hearing Examination for whom Audiologist responded to Hearing Loss question
Arm/Group Title As-Treated No Growth Hormone As-Treated Growth Hormone
Hide Arm/Group Description:
Patients who never received growth hormone
Patients who received Humatrope or another brand of growth hormone
Overall Number of Participants Analyzed 19 52
Measure Type: Number
Unit of Measure: participants
Conductive Hearing Loss 1 7
Sensorineural Hearing Loss 8 15
Mixed Hearing Loss 2 9
Unspecified Hearing Loss 1 1
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection As-Treated No Growth Hormone, As-Treated Growth Hormone
Comments Comparison of proportion of patients with any category of hearing loss between As-Treated Growth Hormone group and As-Treated No Growth Hormone.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.999
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
9.Secondary Outcome
Title Fasting Glucose, Change From Baseline
Hide Description Change from core study baseline to addendum 2 maximum.
Time Frame At core study baseline, and at end of 4-year addendum
Hide Outcome Measure Data
Hide Analysis Population Description
Patients who were followed for at least 4 years without growth hormone treatment or who received growth hormone for at least 4 years, and who were treated as randomized and had core study baseline and addendum glucose metabolism data.
Arm/Group Title Treated-As-Randomized Control Treated-As-Randomized Humatrope
Hide Arm/Group Description:
Patients in As-Randomized Control group who at each observed time point remained untreated with growth hormone.
Patients in As-Randomized Humatrope group who received Humatrope treatment
Overall Number of Participants Analyzed 20 36
Least Squares Mean (Standard Error)
Unit of Measure: mg / dL
5.495  (2.455) 3.003  (1.830)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Treated-As-Randomized Control, Treated-As-Randomized Humatrope
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.419
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.492
Confidence Interval 95%
-8.631 to 3.646
Estimation Comments Direction of estimated treatment effect is Humatrope minus Control
10.Secondary Outcome
Title Maximum Fasting Glucose Value
Hide Description Maximum measured value over addendum. In special cases an additional measurement is taken at 2 years.
Time Frame At start and through end of 4-year addendum (up to an additional 2 years)
Hide Outcome Measure Data
Hide Analysis Population Description
Patients with addendum data who were followed for at least 4 years without growth hormone treatment (and never received growth hormone) or who received growth hormone for at least 4 years.
Arm/Group Title As-Treated No Growth Hormone As-Treated Growth Hormone
Hide Arm/Group Description:
Patients who never received growth hormone
Patients who received Humatrope or another brand of growth hormone
Overall Number of Participants Analyzed 21 39
Mean (Standard Deviation)
Unit of Measure: milligrams per deciliter (mg/dL)
85.2  (6.6) 85.2  (10.4)
11.Secondary Outcome
Title Number of Participants With Any Abnormal Fasting Glucose Value
Hide Description Indicates if patient had any measured value exceeding threshold of normality at any visit during addendum. Abnormal Fasting Glucose=Fasting Glucose >=100 milligrams per deciliter (mg/dL).
Time Frame At start and through end of 4-year addendum
Hide Outcome Measure Data
Hide Analysis Population Description
Patients with any Addendum 2 glucose metabolism data
Arm/Group Title As-Treated No Growth Hormone As-Treated Growth Humatrope
Hide Arm/Group Description:
Patients who never received growth hormone
Patients who received Humatrope or another brand of growth hormone
Overall Number of Participants Analyzed 21 39
Measure Type: Number
Unit of Measure: participants
0 3
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection As-Treated No Growth Hormone, As-Treated Growth Humatrope
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.545
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
12.Secondary Outcome
Title Maximum Fasting Insulin Values
Hide Description Maximum measured value over addendum. In special cases an additional measurement is taken at 2 years.
Time Frame At start and through end of 4-year addendum (up to an additional 2 years)
Hide Outcome Measure Data
Hide Analysis Population Description
Patients with addendum data who were followed for at least 4 years without growth hormone treatment (and never received growth hormone) or who received growth hormone for at least 4 years.
Arm/Group Title As-Treated No Growth Hormone As-Treated Growth Hormone
Hide Arm/Group Description:
Patients who never received growth hormone
Patients who received Humatrope or another brand of growth hormone
Overall Number of Participants Analyzed 21 40
Mean (Standard Deviation)
Unit of Measure: micro International Units per milliliter
9.5  (10.8) 9.7  (9.3)
13.Secondary Outcome
Title Number of Participants With Any Abnormal Fasting Insulin Value
Hide Description Indicates if patient had any measured value exceeding threshold of normality at any visit during addendum. Abnormal Fasting Insulin = Fasting Insulin >=35 micro International Units per milliliter (uIU/mL).
Time Frame At start and through end of 4-year addendum
Hide Outcome Measure Data
Hide Analysis Population Description
Patients with any Addendum 2 glucose metabolism data
Arm/Group Title As-Treated No Growth Hormone As-Treated Growth Humatrope
Hide Arm/Group Description:
Patients who never received growth hormone
Patients who received Humatrope or another brand of growth hormone
Overall Number of Participants Analyzed 21 40
Measure Type: Number
Unit of Measure: participants
1 2
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection As-Treated No Growth Hormone, As-Treated Growth Humatrope
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.999
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
14.Secondary Outcome
Title Minimum Fasting Glucose/Insulin Ratio Values
Hide Description Minimum measured value over addendum. In special cases an additional measurement is taken at 2 years.
Time Frame At start and through end of 4-year addendum (up to an additional 2 years)
Hide Outcome Measure Data
Hide Analysis Population Description
Patients with addendum data who were followed for at least 4 years without growth hormone treatment (and never received growth hormone) or who received growth hormone for at least 4 years.
Arm/Group Title As-Treated No Growth Hormone As-Treated Growth Hormone
Hide Arm/Group Description:
Patients who never received growth hormone
Patients who received Humatrope or another brand of growth hormone
Overall Number of Participants Analyzed 21 38
Mean (Standard Deviation)
Unit of Measure: milligrams per 10^-4 Units (mg/[10^-4]U)
12.5  (6.0) 12.2  (5.3)
15.Secondary Outcome
Title Number of Participants With Any Abnormal Fasting Glucose/Insulin Ratio Value
Hide Description Indicates if patient had any measured value below threshold of normality at any visit during addendum. Abnormal Fasting Glucose/Insulin Ratio = Fasting Glucose/Insulin Ratio <=4.5 milligrams per 10^-4 Units (mg/10^-4U).
Time Frame At start and through end of 4-year addendum
Hide Outcome Measure Data
Hide Analysis Population Description
Patients with any Addendum 2 glucose metabolism data. Calculated only for patients with fasting blood <100 mg/dL.
Arm/Group Title As-Treated No Growth Hormone As-Treated Growth Hormone
Hide Arm/Group Description:
Patients who never received growth hormone
Patients who received Humatrope or another brand of growth hormone
Overall Number of Participants Analyzed 21 38
Measure Type: Number
Unit of Measure: participants
1 3
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection As-Treated No Growth Hormone, As-Treated Growth Hormone
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.999
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
16.Secondary Outcome
Title Glycosylated Hemoglobin, Change From Baseline
Hide Description Change from core study baseline to addendum 2 maximum.
Time Frame At core study baseline, and at end of 4-year addendum
Hide Outcome Measure Data
Hide Analysis Population Description
Patients who were followed for at least 4 years without growth hormone treatment or who received growth hormone for at least 4 years, and who were treated as randomized and had core study baseline and addendum glucose metabolism data.
Arm/Group Title Treated-As-Randomized Control Treated-As-Randomized Humatrope
Hide Arm/Group Description:
Patients in As-Randomized Control group who at each observed time point remained untreated with growth hormone.
Patients in the As-Randomized Humatrope group who received Humatrope
Overall Number of Participants Analyzed 20 36
Least Squares Mean (Standard Error)
Unit of Measure: percent (%)
0.215  (0.077) 0.208  (0.057)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Treated-As-Randomized Control, Treated-As-Randomized Humatrope
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.945
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.007
Confidence Interval 95%
-0.199 to 0.186
Estimation Comments Direction of estimated treatment effect is Humatrope minus Control
17.Secondary Outcome
Title Maximum Glycosylated Hemoglobin
Hide Description Maximum measured value over addendum. In special cases an additional measurement is taken at 2 years.
Time Frame At start and through end of 4-year addendum (up to an additional 2 years)
Hide Outcome Measure Data
Hide Analysis Population Description
Patients with addendum data who were followed for at least 4 years without growth hormone treatment (and never received growth hormone) or who received growth hormone for at least 4 years.
Arm/Group Title As-Treated No Growth Hormone As-Treated Growth Hormone
Hide Arm/Group Description:
Patients who never received growth hormone
Patients who received Humatrope or another brand of growth hormone
Overall Number of Participants Analyzed 21 40
Mean (Standard Deviation)
Unit of Measure: percent (%)
5.0  (0.5) 5.0  (0.4)
18.Secondary Outcome
Title Number of Participants With Any Abnormal Glycosylated Hemoglobin (HbA1c) Value
Hide Description Indicates if patient had any measured value exceeding threshold of normality at any visit during addendum. Abnormal Glycosylated Hemoglobin = HbA1c ≥6.8% (up until 11-May-1998); and then HbA1c ≥6.1% (from 19-May-1998 onwards).
Time Frame At start and through end of 4-year addendum
Hide Outcome Measure Data
Hide Analysis Population Description
Patients with any Addendum 2 glucose metabolism data.
Arm/Group Title As-Treated No Growth Hormone As-Treated Growth Hormone
Hide Arm/Group Description:
Patients who never received growth hormone
Patients who received Humatrope or another brand of growth hormone
Overall Number of Participants Analyzed 21 40
Measure Type: Number
Unit of Measure: participants
0 0
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection As-Treated No Growth Hormone, As-Treated Growth Hormone
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments P-value cannot be computed since no patients had abnormal result in either comparison group.
Method Fisher Exact
Comments [Not Specified]
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Treated-As-Randomized Control Treated-As-Randomized Humatrope
Hide Arm/Group Description Patients in the As-Randomized Control group who at each observed time point remained untreated with growth hormone. Patients in the As-Randomized Humatrope group who received Humatrope
All-Cause Mortality
Treated-As-Randomized Control Treated-As-Randomized Humatrope
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Treated-As-Randomized Control Treated-As-Randomized Humatrope
Affected / at Risk (%) Affected / at Risk (%)
Total   10/54 (18.52%)   22/74 (29.73%) 
Blood and lymphatic system disorders     
Anemia iron deficiency  1  0/54 (0.00%)  1/74 (1.35%) 
Hypochromic microcytic anemia  1  0/54 (0.00%)  1/74 (1.35%) 
Idiopathic thrombocytopenic purpura  1  1/54 (1.85%)  0/74 (0.00%) 
Cardiac disorders     
Cardiac arrest  1  1/54 (1.85%)  0/74 (0.00%) 
Infections and infestations     
Cellulitis of foot  1  0/54 (0.00%)  1/74 (1.35%) 
Gastroenteritis  1  0/54 (0.00%)  1/74 (1.35%) 
Otitis media  1  0/54 (0.00%)  1/74 (1.35%) 
Pneumonia  1  1/54 (1.85%)  0/74 (0.00%) 
Pyelonephritis  1  0/54 (0.00%)  1/74 (1.35%) 
Stomach flu  1  0/54 (0.00%)  1/74 (1.35%) 
Viral meningitis  1  0/54 (0.00%)  1/74 (1.35%) 
Injury, poisoning and procedural complications     
Arm fracture  1  0/54 (0.00%)  2/74 (2.70%) 
Wrist fracture  1  0/54 (0.00%)  1/74 (1.35%) 
Investigations     
Colonoscopy  1  0/54 (0.00%)  1/74 (1.35%) 
Cystoscopy  1  0/54 (0.00%)  1/74 (1.35%) 
Metabolism and nutrition disorders     
Dehydration  1  0/54 (0.00%)  1/74 (1.35%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Brain neoplasm benign  1  0/54 (0.00%)  1/74 (1.35%) 
Skin and subcutaneous tissue disorders     
Psoriasis  1  0/54 (0.00%)  1/74 (1.35%) 
Pustular psoriasis  1  0/54 (0.00%)  1/74 (1.35%) 
Surgical and medical procedures     
Adenoidectomy  1  0/54 (0.00%)  1/74 (1.35%) 
Aorta coarctation repair  1  0/54 (0.00%)  1/74 (1.35%) 
Appendectomy  1  2/54 (3.70%)  0/74 (0.00%) 
Chest wall repair  1  1/54 (1.85%)  0/74 (0.00%) 
Cholesteatoma removal  1  0/54 (0.00%)  1/74 (1.35%) 
Dental surgery NOS  1  0/54 (0.00%)  1/74 (1.35%) 
Eye muscle operation  1  0/54 (0.00%)  1/74 (1.35%) 
Heart valve operation  1  0/54 (0.00%)  1/74 (1.35%) 
Mastoid operation  1  0/54 (0.00%)  1/74 (1.35%) 
Mastoidectomy  1  0/54 (0.00%)  1/74 (1.35%) 
Orchiectomy  1  0/54 (0.00%)  1/74 (1.35%) 
Pterygium operation  1  1/54 (1.85%)  1/74 (1.35%) 
Scar removal  1  1/54 (1.85%)  0/74 (0.00%) 
Surgical procedure  1  1/54 (1.85%)  0/74 (0.00%) 
Tooth extraction  1  1/54 (1.85%)  0/74 (0.00%) 
Tympanoplasty  1  0/54 (0.00%)  3/74 (4.05%) 
Vascular disorders     
Aortic aneurysm rupture  1  1/54 (1.85%)  0/74 (0.00%) 
Thrombophlebitis  1  1/54 (1.85%)  0/74 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 11.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Treated-As-Randomized Control Treated-As-Randomized Humatrope
Affected / at Risk (%) Affected / at Risk (%)
Total   53/54 (98.15%)   74/74 (100.00%) 
Ear and labyrinth disorders     
Ear ache  1  6/54 (11.11%)  10/74 (13.51%) 
Ear discharge  1  0/54 (0.00%)  4/74 (5.41%) 
Ear pain  1  3/54 (5.56%)  14/74 (18.92%) 
Earache  1  5/54 (9.26%)  8/74 (10.81%) 
Hearing loss  1  2/54 (3.70%)  7/74 (9.46%) 
Sensorineural hearing loss  1  3/54 (5.56%)  0/74 (0.00%) 
Tympanosclerosis  1  3/54 (5.56%)  0/74 (0.00%) 
Endocrine disorders     
Hypothyroidism  1  7/54 (12.96%)  13/74 (17.57%) 
Eye disorders     
Conjunctivitis  1  2/54 (3.70%)  4/74 (5.41%) 
Myopia  1  3/54 (5.56%)  4/74 (5.41%) 
Gastrointestinal disorders     
Abdominal pain  1  9/54 (16.67%)  9/74 (12.16%) 
Ache stomach  1  0/54 (0.00%)  4/74 (5.41%) 
Diarrhea  1  11/54 (20.37%)  12/74 (16.22%) 
Nausea  1  5/54 (9.26%)  13/74 (17.57%) 
Stomach ache  1  7/54 (12.96%)  7/74 (9.46%) 
Stomach cramps  1  4/54 (7.41%)  4/74 (5.41%) 
Stomach pain  1  2/54 (3.70%)  6/74 (8.11%) 
Upset stomach  1  3/54 (5.56%)  5/74 (6.76%) 
Vomiting  1  21/54 (38.89%)  29/74 (39.19%) 
General disorders     
Chest pain  1  4/54 (7.41%)  1/74 (1.35%) 
Fatigue  1  4/54 (7.41%)  1/74 (1.35%) 
Fever  1  20/54 (37.04%)  36/74 (48.65%) 
Pain  1  0/54 (0.00%)  4/74 (5.41%) 
Immune system disorders     
Hay fever  1  1/54 (1.85%)  7/74 (9.46%) 
Multiple allergies  1  1/54 (1.85%)  6/74 (8.11%) 
Infections and infestations     
Bladder infection  1  3/54 (5.56%)  4/74 (5.41%) 
Bronchitis  1  5/54 (9.26%)  7/74 (9.46%) 
Chest cold  1  0/54 (0.00%)  7/74 (9.46%) 
Chickenpox  1  5/54 (9.26%)  8/74 (10.81%) 
Cold  1  39/54 (72.22%)  42/74 (56.76%) 
Cold symptoms  1  4/54 (7.41%)  7/74 (9.46%) 
Common cold  1  4/54 (7.41%)  5/74 (6.76%) 
Ear infection  1  12/54 (22.22%)  27/74 (36.49%) 
Eye infection  1  3/54 (5.56%)  9/74 (12.16%) 
Flu  1  20/54 (37.04%)  36/74 (48.65%) 
Flu syndrome  1  6/54 (11.11%)  15/74 (20.27%) 
Gastroenteritis  1  2/54 (3.70%)  6/74 (8.11%) 
Head cold  1  9/54 (16.67%)  18/74 (24.32%) 
Impetigo  1  4/54 (7.41%)  6/74 (8.11%) 
Otitis externa  1  6/54 (11.11%)  13/74 (17.57%) 
Otitis media  1  13/54 (24.07%)  31/74 (41.89%) 
Pharyngitis  1  8/54 (14.81%)  11/74 (14.86%) 
Rhinitis  1  11/54 (20.37%)  17/74 (22.97%) 
Sinus infection  1  1/54 (1.85%)  5/74 (6.76%) 
Sinusitis  1  3/54 (5.56%)  7/74 (9.46%) 
Stomach flu  1  6/54 (11.11%)  6/74 (8.11%) 
Streptococcal sore throat  1  4/54 (7.41%)  9/74 (12.16%) 
Throat infection  1  7/54 (12.96%)  8/74 (10.81%) 
Tonsillitis  1  5/54 (9.26%)  6/74 (8.11%) 
Upper respiratory infection  1  14/54 (25.93%)  13/74 (17.57%) 
Upper respiratory tract infection  1  9/54 (16.67%)  8/74 (10.81%) 
Urinary tract infection  1  3/54 (5.56%)  5/74 (6.76%) 
Injury, poisoning and procedural complications     
Accidental overdose  1  0/54 (0.00%)  5/74 (6.76%) 
Head injury  1  3/54 (5.56%)  2/74 (2.70%) 
Musculoskeletal and connective tissue disorders     
Knee pain  1  1/54 (1.85%)  8/74 (10.81%) 
Leg pain  1  1/54 (1.85%)  4/74 (5.41%) 
Low back pain  1  4/54 (7.41%)  3/74 (4.05%) 
Osteopenia  1  4/54 (7.41%)  2/74 (2.70%) 
Scoliosis  1  8/54 (14.81%)  6/74 (8.11%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Naevus  1  2/54 (3.70%)  5/74 (6.76%) 
Nervous system disorders     
Dizziness  1  4/54 (7.41%)  7/74 (9.46%) 
Headache  1  25/54 (46.30%)  46/74 (62.16%) 
Intermittent headache  1  3/54 (5.56%)  12/74 (16.22%) 
Psychiatric disorders     
Depression  1  4/54 (7.41%)  6/74 (8.11%) 
Reproductive system and breast disorders     
Cramps menstrual  1  2/54 (3.70%)  4/74 (5.41%) 
Dysmenorrhea  1  2/54 (3.70%)  4/74 (5.41%) 
Menstrual cramps  1  7/54 (12.96%)  7/74 (9.46%) 
Primary ovarian failure  1  4/54 (7.41%)  5/74 (6.76%) 
Spotting vaginal  1  4/54 (7.41%)  0/74 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Asthma  1  0/54 (0.00%)  4/74 (5.41%) 
Congestion nasal  1  2/54 (3.70%)  5/74 (6.76%) 
Cough  1  14/54 (25.93%)  27/74 (36.49%) 
Coughing  1  2/54 (3.70%)  5/74 (6.76%) 
Epistaxis  1  3/54 (5.56%)  2/74 (2.70%) 
Nasal congestion  1  8/54 (14.81%)  17/74 (22.97%) 
Nasal discharge  1  3/54 (5.56%)  2/74 (2.70%) 
Nose bleed  1  1/54 (1.85%)  5/74 (6.76%) 
Sinus congestion  1  5/54 (9.26%)  7/74 (9.46%) 
Sore throat  1  28/54 (51.85%)  37/74 (50.00%) 
Throat sore  1  1/54 (1.85%)  6/74 (8.11%) 
Skin and subcutaneous tissue disorders     
Dry skin  1  1/54 (1.85%)  8/74 (10.81%) 
Eczema  1  4/54 (7.41%)  4/74 (5.41%) 
Ingrown toe nail  1  3/54 (5.56%)  2/74 (2.70%) 
Rash  1  8/54 (14.81%)  8/74 (10.81%) 
Surgical and medical procedures     
Dental surgery NOS  1  1/54 (1.85%)  4/74 (5.41%) 
Dental treatment  1  8/54 (14.81%)  6/74 (8.11%) 
Ear tube insertion  1  1/54 (1.85%)  4/74 (5.41%) 
Mole excision  1  2/54 (3.70%)  5/74 (6.76%) 
Myringotomy  1  1/54 (1.85%)  8/74 (10.81%) 
Tooth extraction  1  3/54 (5.56%)  3/74 (4.05%) 
Tympanoplasty  1  0/54 (0.00%)  4/74 (5.41%) 
Vascular disorders     
Aortic dilatation  1  3/54 (5.56%)  1/74 (1.35%) 
Blood pressure high  1  3/54 (5.56%)  1/74 (1.35%) 
Hypertension  1  1/54 (1.85%)  7/74 (9.46%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 11.0
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.
Results Point of Contact
Name/Title: Chief Medical Officer
Organization: Eli Lilly and Company
Phone: 1-800-545-5979
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
First Submitted: September 12, 2005
First Posted: September 19, 2005
Results First Submitted: December 1, 2008
Results First Posted: January 27, 2010
Last Update Posted: January 27, 2010