Effect of Biosynthetic Growth Hormone and/or Ethinyl Estradiol on Adult Height in Patients With Turner Syndrome
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|ClinicalTrials.gov Identifier: NCT00001221|
Recruitment Status : Completed
First Posted : November 4, 1999
Last Update Posted : March 4, 2008
|First Submitted Date ICMJE||November 3, 1999|
|First Posted Date ICMJE||November 4, 1999|
|Last Update Posted Date||March 4, 2008|
|Study Start Date ICMJE||September 1987|
|Primary Completion Date||Not Provided|
|Current Primary Outcome Measures ICMJE||Not Provided|
|Original Primary Outcome Measures ICMJE||Not Provided|
|Current Secondary Outcome Measures ICMJE||Not Provided|
|Original Secondary Outcome Measures ICMJE||Not Provided|
|Current Other Pre-specified Outcome Measures||Not Provided|
|Original Other Pre-specified Outcome Measures||Not Provided|
|Brief Title ICMJE||Effect of Biosynthetic Growth Hormone and/or Ethinyl Estradiol on Adult Height in Patients With Turner Syndrome|
|Official Title ICMJE||A Double-Blind, Randomized, Placebo-Controlled Trial of the Effect of Biosynthetic Growth Hormone and/or Ethinyl Estradiol on Adult Height in Patients With Turner Syndrome|
Turners Syndrome is a genetic condition in females that is a result of abnormal chromosomes. Girls with Turner syndrome are very short as children and as adults. Although their growth hormone secretion is almost always normal, giving injections of growth hormone to Turner syndrome girls may increase their rate of growth. In addition, most girls with Turner syndrome do not have normal ovaries.
In normal girls the ovaries begin producing small amounts of the female sex hormone, estrogen at about 11 - 12 years of age. As girls grow older the level of estrogen increases. Estrogen is responsible for the changes in girls known as feminization. During feminization the hips grow wider, the breasts develop, there is an increase in the rate of growth, and eventually girls experience their first menstrual period.
This study was designed to evaluate the effect of low dose estrogen, growth hormone, and the combination of low dose estrogen and growth hormone on adult height in girls with Turner syndrome. Patients will be entered into the study from ages 5 to 12 and will be randomly placed into one of four groups.
Once started, the treatment will continue until the patients approach their adult height, and growth slows to less than 1/2 inch over the preceding year. This usually occurs by the age of 15 or 16.
Patients will be seen at the outpatient clinic every 6 months during the study and will receive a routine check-up with blood and urine tests, and hand/wrist X-rays to determine bone age. On patient's yearly visits they will have the density of bone measured in their spine and forearm.
Adult women with Turner's syndrome are quite short. Several treatments have been used to increase growth rate in these patients. They include oxandrolone (1), growth hormone (2, 3), and low dose estrogen (4). However, the ability of these hormone treatments to increase adult height has never been evaluated in controlled clinical trials.
We propose to evaluate the effect on adult height of low dose estrogen, growth hormone, and the combination of low dose estrogen and growth hormone. Patients will be entered into the study from ages 5 to 12 and will be assigned randomly to one of the four groups (the 3 above treatment groups or placebo). The randomized assignment will be double-blind throughout the study. Treatment will be maintained to adult height (the first height measurement at which the preceding annual growth rate was < 1.5 cm). Beginning at age 12, the estrogen treatment in all 4 groups will be changed to a standardized regimen of increasing estrogen dose, so that all children in the study will undergo secondary sexual changes at an appropriate age.
In addition, the study will assess the effect of growth hormone and estrogen treatment on bone density and, in a parallel, separate, study, the effect of treatment on cognition and learning ability.
|Study Type ICMJE||Interventional|
|Study Phase ICMJE||Phase 2|
|Study Design ICMJE||Primary Purpose: Treatment|
|Intervention ICMJE||Drug: Growth Hormone (Humatrope)|
|Study Arms ICMJE||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Completed|
|Original Enrollment ICMJE||Same as current|
|Study Completion Date ICMJE||September 2003|
|Primary Completion Date||Not Provided|
|Eligibility Criteria ICMJE||
All subjects will be outpatients.
Patients must be females with Turner's syndrome diagnosed by leukocyte karyotype
Chronologic age greater than or equal to 5 years.
Prepubertal Tanner I status. If breast development is Tanner II or III, demonstration of castrate status through measurement of serum FSH (greater than 12 MIU/ML).
All patients must be below the 10th percentile for chronologic age.
Patients must have at least 6 months accurate, growth measurements available for calculation of pre-study growth velocity. Pretreatment measurements must be obtained during a time when the patient is not receiving a potential growth-promoting agent.
Patients judged to be thyroxine deficient must have replacement which has resulted in normal thyroid function tests over the three-month period prior to enrollment (T4, T3, Thyroid Stimulating Hormone).
Patients and/or parents or legal guardians of patients must sign an informed consent statement. Assent should be obtained from all patients competent to understand the protocol. Local IRB requirements apply.
Patients who have received any form of human growth hormone within the past 3 months, or who have received a cumulative course of therapy totaling greater than one year.
Patients who have received treatment with estrogen or androgen in the past three months or who have received a cumulative course of therapy totaling greater than one year.
Patients who have any Y component in their chromosome analysis.
Patients with a chronologic age greater than 12 years.
Patients with a bone age greater than 12 years.
Patients who have clinically significant cardiac, pulmonary, gastrointestinal, hepatic or renal disease or who have had any malignancy.
Patients who have significant hematuria or proteinuria in pretherapy evaluation.
Patients who have diabetes mellitus.
Patients who have any active chronic infection (tuberculosis).
Patients who are taking amphetamines or any other drugs known to interfere with growth hormone secretion or actions.
Patients who are poor medical, psychological, or psychiatric risks for whom, in the opinion of the principal investigator, the investigational drug would be unwise.
Patients whose parents are substance abusers, nor those who come from homes in which appropriate emotional development may be limited.
Patients who cannot be seen on the schedule required by the protocol.
|Ages ICMJE||Child, Adult, Older Adult|
|Accepts Healthy Volunteers ICMJE||No|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Listed Location Countries ICMJE||United States|
|Removed Location Countries|
|NCT Number ICMJE||NCT00001221|
|Other Study ID Numbers ICMJE||870152
|Has Data Monitoring Committee||Not Provided|
|U.S. FDA-regulated Product||Not Provided|
|IPD Sharing Statement ICMJE||Not Provided|
|Responsible Party||Not Provided|
|Study Sponsor ICMJE||Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)|
|Collaborators ICMJE||Not Provided|
|Investigators ICMJE||Not Provided|
|PRS Account||National Institutes of Health Clinical Center (CC)|
|Verification Date||September 2003|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP