Somatropin Treatment to Final Height in Turner Syndrome

Phase 3CompletedNCT00191113

Eli Lilly and Company154 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

154

Conditions

Turner Syndrome

Interventions

SomatropinDRUG

0.05 mg/kg/dose by subcutaneous injection 6 times per week, until Core study completion criteria are met (protocol final height).

Ethinyl estradiolDRUG

escalating doses 2.5-20.0 mcg tablets daily after age 13 and at least one year on study, continuing until Core study completion criteria are met.

Medroxyprogesterone acetateDRUG

10 mg tablets, ten days monthly, after age 15, continuing until Core study completion criteria are met.

Eligibility

Sex: FEMALEMin age: 7 YearsMax age: 13 Years

Medical Language ↔ Plain English

Inclusion Criteria: * 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 Exclusion Criteria: * prior treatment with growth hormone * presence of a Y component in karyotype with gonads in situ * diabetes mellitus

Locations (14)

Outcomes

Primary Outcomes

Height Standard Deviation Score (SDS) (National Center for Health Statistics [NCHS]), Change From Baseline to Last Measurement, As Randomized Population

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

Height Standard Deviation Score (SDS) (National Center for Health Statistics [NCHS]), Last Measurement After Attainment of Final Height

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

Secondary Outcomes

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

Height (Centimeters [cm])

Most mature measurement available, at or after attainment of Final Height.

Data from ClinicalTrials.gov

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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.

Calgary, Alberta, Canada

Edmonton, Alberta, Canada

Vancouver, British Columbia, Canada

Winnipeg, Manitoba, Canada

Halifax, Nova Scotia, Canada

Hamilton, Ontario, Canada

Kingston, Ontario, Canada

London, Ontario, Canada

Ottawa, Ontario, Canada

Toronto, Ontario, Canada

...and 4 more locations

Time frame: every 3 months during core study, and at start and end of 4-year addendum

Number of Participants With an Abnormal Pure Tone Audiometry, Audiologist Assessment

Time frame: at completion of core study or beginning of addendum

Number of Participants With Abnormal Speech Audiometry, Audiologist Assessment

Time frame: at completion of core study or beginning of addendum

Number of Participants With Abnormal Impedance Tympanometry, Audiologist Assessment

Time frame: at completion of core study or beginning of addendum

Number of Participants With Hearing Loss, Audiologist Assessment

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

Fasting Glucose, Change From Baseline

Change from core study baseline to addendum 2 maximum.

Time frame: At core study baseline, and at end of 4-year addendum

Maximum Fasting Glucose Value

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)

Number of Participants With Any Abnormal Fasting Glucose Value

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

Maximum Fasting Insulin Values

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)

Number of Participants With Any Abnormal Fasting Insulin Value

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

Minimum Fasting Glucose/Insulin Ratio Values

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)

Number of Participants With Any Abnormal Fasting Glucose/Insulin Ratio Value

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

Glycosylated Hemoglobin, Change From Baseline

Change from core study baseline to addendum 2 maximum.

Time frame: At core study baseline, and at end of 4-year addendum

Maximum Glycosylated Hemoglobin

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)

Number of Participants With Any Abnormal Glycosylated Hemoglobin (HbA1c) Value

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