Somatropin Treatment to Final Height in Turner Syndrome - Full Text View

Sponsored by:	Eli Lilly and Company
Information provided by:	Eli Lilly and Company
ClinicalTrials.gov Identifier:	NCT00191113

Purpose

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 treatment in promoting linear growth to final height.

Condition	Intervention	Phase
Turner Syndrome	Drug: Somatropin Drug: Ethinyl estradiol Drug: Medroxyprogesterone acetate	Phase III

Genetics Home Reference related topics: Turner syndrome

MedlinePlus related topics: Turner Syndrome

Drug Information available for: Depogen Estradiol Estradiol 3-benzoate Estradiol acetate Estradiol cypionate Estradiol dipropionate Estradiol valerate Polyestradiol phosphate Dextrose Ethinyl estradiol Medroxyprogesterone Medroxyprogesterone 17-acetate Somatotropin Somatropin

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study
Official Title:	Humatrope Treatment to Final Height in Turner's Syndrome

Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:

Height SDS (NCHS), Change from Baseline [ Time Frame: Most mature measurement available ] [ Designated as safety issue: No ]
Height SDS (NCHS) [ Time Frame: Most mature measurement available, at or after attainment of final height ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Pure Tone Audiometry, Normal v Abnormal result [ Time Frame: At or after completion of core study ] [ Designated as safety issue: Yes ]
Speech Audiometry, Normal v Abnormal result [ Time Frame: At or after completion of core study ] [ Designated as safety issue: Yes ]
Impedance Tympanometry, Normal v Abnormal result [ Time Frame: At or after completion of core study ] [ Designated as safety issue: Yes ]
Conductive Hearing Loss [ Time Frame: At or after completion of core study ] [ Designated as safety issue: Yes ]
Sensorineural Hearing Loss [ Time Frame: At or after completion of core study ] [ Designated as safety issue: Yes ]
Mixed Hearing Loss [ Time Frame: At or after completion of core study ] [ Designated as safety issue: Yes ]
Fasting Glucose, Change from Baseline [ Time Frame: Maximum value during addendum ] [ Designated as safety issue: Yes ]
Fasting Insulin, Change from Baseline [ Time Frame: Maximum value during addendum ] [ Designated as safety issue: Yes ]
Fasting Glucose/Insulin Ratio, Change from Baseline [ Time Frame: Maximum value during addendum ] [ Designated as safety issue: Yes ]
Glycosylated Hemoglobin, Change from Baseline [ Time Frame: Maximum value during addendum ] [ Designated as safety issue: Yes ]
Fasting Glucose, any Abnormal result [ Time Frame: At any time during addendum ] [ Designated as safety issue: Yes ]
Fasting Insulin, any Abnormal result [ Time Frame: At any time during addendum ] [ Designated as safety issue: Yes ]
Fasting Glucose/Insulin Ratio, any Abnormal result [ Time Frame: At any time during addendum ] [ Designated as safety issue: Yes ]
Glycosylated Hemoglobin, any Abnormal result [ Time Frame: At any time during addendum ] [ Designated as safety issue: Yes ]
Height (cm) [ Time Frame: Most mature measurement available, at or after attainment of final height ] [ Designated as safety issue: No ]
Height SDS (NCHS), Change from Baseline [ Time Frame: Most mature measurement available, at or after attainment of final height ] [ Designated as safety issue: No ]

Enrollment:	162
Study Start Date:	February 1989
Study Completion Date:	December 2007
Primary Completion Date:	December 2007 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Control: No Intervention 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.
Humatrope: Experimental 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: Somatropin 0.05 mg/kg/dose by subcutaneous injection 6 times per week, 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.

Arms

Assigned Interventions

Control: No Intervention

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.

Humatrope: Experimental

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: Somatropin

0.05 mg/kg/dose by subcutaneous injection 6 times per week, 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.

Detailed Description:

A randomized, controlled trial of Humatrope 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.

Eligibility

Ages Eligible for Study:	7 Years to 13 Years
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00191113

Locations

Canada, Alberta
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.
Calgary, Alberta, Canada, T2T 5C7
Canada, British Columbia
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.
Vancouver, British Columbia, Canada, V6H 3V4
Canada, Manitoba
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.
Winnipeg, Manitoba, Canada, R3E 0Z2
Canada, Nova Scotia
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.
Halifax, Nova Scotia, Canada, B3J 3G9
Canada, Ontario
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.
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.
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.
Hamilton, Ontario, Canada, L8S 3Z5
Canada, Quebec
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.
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.
Sherbrooke, Quebec, Canada, J1G 2E8

Sponsors and Collaborators

Eli Lilly and Company

Investigators

Study Director:

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 am - 5 pm Eastern Time (UTC/GMT - 5 hours, EST)

Eli Lilly and Company

More Information

Lilly Clinical Trial Registry This link exits the ClinicalTrials.gov site

Responsible Party:	Eli Lilly and Company ( Chief Medical Officer )
Study ID Numbers:	817/4419, #817 B9R-CA-GDCT Core study, #4419 GDCT/1 Addenda
Study First Received:	September 12, 2005
Last Updated:	September 19, 2008
ClinicalTrials.gov Identifier:	NCT00191113
Health Authority:	Canada: Health Canada; United States: Food and Drug Administration

Keywords provided by Eli Lilly and Company:

syndrome
Turner
Turner's
height
growth
growth hormone

somatropin
short stature
short
hearing
glucose metabolism

Study placed in the following topic categories:

Chromosomal abnormalities
Medroxyprogesterone 17-Acetate
Genital dwarfism
Gonadal Disorders
Estradiol valerate
Chromosome Disorders
Ethinyl Estradiol
Endocrine System Diseases
Estradiol 17 beta-cypionate
Sex Differentiation Disorders
Estradiol
Monosomy X

Turner Syndrome
Gonadal dysgenesis
Urogenital Abnormalities
Genetic Diseases, Inborn
Estradiol 3-benzoate
Turner syndrome
Medroxyprogesterone
Ovarian dwarfism
Endocrinopathy
Polyestradiol phosphate
Congenital Abnormalities
Gonadal Dysgenesis

Additional relevant MeSH terms:

Estrogens
Disease
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Contraceptive Agents
Physiological Effects of Drugs
Contraceptives, Oral
Hormones, Hormone Substitutes, and Hormone Antagonists
Contraceptive Agents, Female

Reproductive Control Agents
Contraceptive Agents, Male
Hormones
Pharmacologic Actions
Pathologic Processes
Therapeutic Uses
Syndrome
Sex Chromosome Disorders
Contraceptives, Oral, Synthetic

ClinicalTrials.gov processed this record on January 16, 2009