Somatropin Treatment to Final Height in Turner Syndrome (GDCT)

Humatrope Treatment to Final Height in Turner's Syndrome

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.

Study Overview

• Status: Completed
• Conditions: Turner Syndrome
• Intervention / Treatment: Drug: Ethinyl estradiol; Drug: Medroxyprogesterone acetate; Drug: Somatropin

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.

• Study Type: Interventional
• Enrollment (Actual): 154
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2T 5C7
      • 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.
    • Edmonton, Alberta, Canada, T6G 2B7
      • 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.
  • British Columbia
    • Vancouver, British Columbia, Canada, V6H 3V4
      • 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.
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3E 0Z2
      • 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.
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3J 3G9
      • 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.
  • Ontario
    • Hamilton, Ontario, Canada, L8S 3Z5
      • 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.
    • Kingston, Ontario, Canada, K7L 3N6
      • 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.
    • London, Ontario, Canada, K7L 3N6
      • 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.
    • Ottawa, Ontario, Canada, K1H 8L1
      • 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.
    • Toronto, Ontario, Canada, M5G 1X8
      • 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.
  • Quebec
    • Montreal, Quebec, Canada, H3H 1P3
      • 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.
    • Montreal, Quebec, Canada, H3T 1C5
      • 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.
    • Sainte-Foy, Quebec, Canada, G1V 4G2
      • 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, J1G 2E8
      • 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.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 7 years to 13 years (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: 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).	Drug: Ethinyl estradiol; 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.; Drug: Medroxyprogesterone acetate; 10 mg tablets, ten days monthly, after age 15, continuing until Core study completion criteria are met.
Experimental: 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).	Drug: Ethinyl estradiol; 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.; Drug: Medroxyprogesterone acetate; 10 mg tablets, ten days monthly, after age 15, continuing until Core study completion criteria are met.; Drug: Somatropin; 0.05 mg/kg/dose by subcutaneous injection 6 times per week, until Core study completion criteria are met (protocol final height).; Other Names: Humatrope; Growth hormone

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	at completion of core study, or at end of 4-year addendum

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Height Standard Deviation Score (SDS) (National Center for Health Statistics [NCHS]), Change From Baseline, As-Treated 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.	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.	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		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	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.	at completion of core study or beginning of addendum
Fasting Glucose, Change From Baseline	Change from core study baseline to addendum 2 maximum.	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.	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).	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.	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).	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.	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).	At start and through end of 4-year addendum
Glycosylated Hemoglobin, Change From Baseline	Change from core study baseline to addendum 2 maximum.	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.	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).	At start and through end of 4-year addendum

Collaborators and Investigators

• Sponsor: Eli Lilly and Company

Publications and helpful links

General Publications

• Lyon AJ, Preece MA, Grant DB. Growth curve for girls with Turner syndrome. Arch Dis Child. 1985 Oct;60(10):932-5. doi: 10.1136/adc.60.10.932.
• Kuczmarski RJ, Ogden CL, Grummer-Strawn LM, Flegal KM, Guo SS, Wei R, Mei Z, Curtin LR, Roche AF, Johnson CL. CDC growth charts: United States. Adv Data. 2000 Jun 8;(314):1-27.
• Hamelin CE, Anglin G, Quigley CA, Deal CL. Genomic imprinting in Turner syndrome: effects on response to growth hormone and on risk of sensorineural hearing loss. J Clin Endocrinol Metab. 2006 Aug;91(8):3002-10. doi: 10.1210/jc.2006-0490. Epub 2006 Jun 6.
• Stephure DK; Canadian Growth Hormone Advisory Committee. Impact of growth hormone supplementation on adult height in turner syndrome: results of the Canadian randomized controlled trial. J Clin Endocrinol Metab. 2005 Jun;90(6):3360-6. doi: 10.1210/jc.2004-2187. Epub 2005 Mar 22.
• Taback SP, Van Vliet G. Health-related quality of life of young adults with Turner syndrome following a long-term randomized controlled trial of recombinant human growth hormone. BMC Pediatr. 2011 May 29;11:49. doi: 10.1186/1471-2431-11-49.

Helpful Links

• Lilly Clinical Trial Registry

Study record dates

Study Major Dates

• Study Start: February 1, 1989
• Primary Completion (Actual): December 1, 2007
• Study Completion (Actual): December 1, 2007

Study Registration Dates

• First Submitted: September 12, 2005
• First Submitted That Met QC Criteria: September 12, 2005
• First Posted (Estimate): September 19, 2005

Study Record Updates

• Last Update Posted (Estimate): January 27, 2010
• Last Update Submitted That Met QC Criteria: December 13, 2009
• Last Verified: December 1, 2009

More Information

Terms related to this study

• Keywords: growth; somatropin; growth hormone; hearing; glucose metabolism; short stature; syndrome; height; short; Turner's; Turner
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Endocrine System Diseases; Disease; Gonadal Disorders; Disorders of Sex Development; Urogenital Abnormalities; Congenital Abnormalities; Genetic Diseases, Inborn; Heart Defects, Congenital; Cardiovascular Abnormalities; Chromosome Disorders; Sex Chromosome Disorders; Sex Chromosome Disorders of Sex Development; Syndrome; Turner Syndrome; Gonadal Dysgenesis; Physiological Effects of Drugs; Antineoplastic Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Estrogens; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptives, Oral; Contraceptive Agents, Female; Contraceptives, Oral, Synthetic; Contraceptives, Oral, Hormonal; Contraceptive Agents, Male; Estradiol; Ethinyl Estradiol; Medroxyprogesterone Acetate; Medroxyprogesterone
• Other Study ID Numbers: 817/4419; #817 B9R-CA-GDCT Core study; #4419 GDCT/1 Addenda