Somatropin Treatment to Final Height in Turner Syndrome
- Conditions
- Turner Syndrome
- Interventions
- Registration Number
- NCT00191113
- Lead Sponsor
- Eli Lilly and Company
- Brief Summary
A randomized, controlled trial in girls with Turner syndrome at least 7 years old and younger than 13 at study entry, to determine the efficacy and safety of Humatrope (somatropin) treatment in promoting linear growth to final height.
- Detailed Description
A randomized, controlled trial of Humatrope (somatropin) treatment in girls with Turner syndrome at least 7 years old and younger than 13 at study entry.
Core study objectives are to determine the efficacy of Humatrope in promoting linear growth to final height in girls with Turner syndrome, and to assess the safety of this treatment. Core study completion criteria (protocol final height) are that the patient has both a height velocity \< 2 cm per year and a bone age of 14 years or greater.
Addendum 1 provides the option of Humatrope treatment to patients who were randomized to the Control arm of the Core study and who discontinued from the study on or after December 19, 1997.
Addendum 2 objectives are: 1) to collect true final height data; 2) to evaluate hearing, tympanic membrane function and other specific areas of interest with respect to the safety of growth hormone therapy in Turner syndrome; 3) to evaluate pancreatic beta cell function (glucose metabolism) in patients previously enrolled in the Core study.
Addendum 3 objective is to determine the parental origin of the retained X chromosome of an appropriate subset of patients currently or previously enrolled in the Core study, and to determine whether this parental origin holds any predictive value for spontaneous growth or for response to growth hormone therapy.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 154
- girl with Turner syndrome
- prepubertal, Tanner stage I breast
- height velocity less than 6 cm/year and height less than or equal to the tenth percentile for sex and age in general population
- at least 6 months (preferably 12 months) of accurate height measurements available for calculation of pre-study height velocity
- if thyroxine deficient, to have received replacement therapy, and for six months prior to enrollment have had normal thyroid function tests
- prior treatment with growth hormone
- presence of a Y component in karyotype with gonads in situ
- diabetes mellitus
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Control Medroxyprogesterone acetate 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). Control Ethinyl estradiol 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 Somatropin 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). Humatrope Ethinyl estradiol 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). Humatrope Medroxyprogesterone acetate 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).
- Primary Outcome Measures
Name Time Method Height Standard Deviation Score (SDS) (National Center for Health Statistics [NCHS]), Change From Baseline to Last Measurement, As Randomized Population Baseline, and end of 4-year addendum 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.
Height Standard Deviation Score (SDS) (National Center for Health Statistics [NCHS]), Last Measurement After Attainment of Final Height at completion of core study, or at end of 4-year addendum 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.
- Secondary Outcome Measures
Name Time Method Height Standard Deviation Score (SDS) (National Center for Health Statistics [NCHS]), Change From Baseline, As-Treated Population every 3 months during core study, and at start and end of 4-year addendum 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.
Height (Centimeters [cm]) every 3 months during core study, and at start and end of 4-year addendum Most mature measurement available, at or after attainment of Final Height.
Number of Participants With an Abnormal Pure Tone Audiometry, Audiologist Assessment at completion of core study or beginning of addendum Number of Participants With Abnormal Speech Audiometry, Audiologist Assessment at completion of core study or beginning of addendum Number of Participants With Abnormal Impedance Tympanometry, Audiologist Assessment at completion of core study or beginning of addendum Number of Participants With Hearing Loss, Audiologist Assessment at completion of core study or beginning of addendum 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.
Fasting Glucose, Change From Baseline At core study baseline, and at end of 4-year addendum Change from core study baseline to addendum 2 maximum.
Maximum Fasting Glucose Value At start and through end of 4-year addendum (up to an additional 2 years) Maximum measured value over addendum. In special cases an additional measurement is taken at 2 years.
Number of Participants With Any Abnormal Fasting Glucose Value At start and through end of 4-year addendum 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).
Maximum Fasting Insulin Values At start and through end of 4-year addendum (up to an additional 2 years) Maximum measured value over addendum. In special cases an additional measurement is taken at 2 years.
Number of Participants With Any Abnormal Fasting Insulin Value At start and through end of 4-year addendum 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).
Minimum Fasting Glucose/Insulin Ratio Values At start and through end of 4-year addendum (up to an additional 2 years) Minimum measured value over addendum. In special cases an additional measurement is taken at 2 years.
Number of Participants With Any Abnormal Fasting Glucose/Insulin Ratio Value At start and through end of 4-year addendum 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).
Glycosylated Hemoglobin, Change From Baseline At core study baseline, and at end of 4-year addendum Change from core study baseline to addendum 2 maximum.
Maximum Glycosylated Hemoglobin At start and through end of 4-year addendum (up to an additional 2 years) Maximum measured value over addendum. In special cases an additional measurement is taken at 2 years.
Number of Participants With Any Abnormal Glycosylated Hemoglobin (HbA1c) Value At start and through end of 4-year addendum 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).
Trial Locations
- Locations (1)
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri 9 am - 5 pm Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
🇨🇦Sherbrooke, Quebec, Canada