OsteoporosisPhase 2NCT00013546
Hormone Replacement Therapy to Treat Turner Syndrome
A Phase 2 study testing TMTDS in people with Osteoporosis and Turner's Syndrome, run by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) at 1 site in United States.
Trial summary
This study will evaluate the effects of hormone replacement therapy on patients with Turner syndrome (TS)-a genetic disorder in females in which part or all of one X chromosome is missing. Read more about this study
- Who is it for?
- Any age, women only
- Conditions the study is for
- Osteoporosis, Turner's Syndrome
- What is being tested?
- TMTDS
- How many people
- 92 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2001to Dec 2002
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- Women only
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Girls and women with TS diagnosed by karyotype or other genetic evidence of X-chromosome defects and ovarian failure (diagnosed by failure to enter puberty spontaneously by age 18 or 2nd degree amenorrhea greater than 6 months and FSH greater than 40 mIU/ml)
- Subjects with TS who have been previously exposed to estrogen and progestin effect, either endogenous or exogenous by medical treatment, sufficient to establish secondary sexual development and menses
- Subjects with TS - ages 14 to 50, who have completed near final height, as demonstrated by a bone age of greater than or equal to 14 years
Who cannot join
- Chronological or bone age of less than 14 years
- Chronological age greater than 50 years
- Chromosomal disorders in addition to TS
- Absence of 2nd degree sexual development
- Growth hormone or androgen treatment within 6 months of starting study.
- Testosterone level greater than normal range for age.
- Contraindications to the use of estrogen, progestin or androgens: Neoplasia; Hypercoagulation disorder; Pregnancy; Gall bladder, biliary or liver parenchymal disease (evidenced by jaundice, gastrointestinal symptomatology, other clinical evidence of cholelithiasis or hepatitis); Hypertriglyceridemia (TGs greater than 300); Active coronary disease (evidenced by documented MI or coronary angiography.
- Mental or physical disability, which in the estimation of study investigators, prevents a candidate from participation in study.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institute of Child Health and Human Development (NICHD)
Bethesda, Maryland, 20892
About this study
Official title: Turner Syndrome: Hormone Replacement Therapy
This study will evaluate the effects of hormone replacement therapy on patients with Turner syndrome (TS)-a genetic disorder in females in which part or all of one X chromosome is missing. Most girls and women with TS have underdeveloped ovaries-the female reproductive organs that produce the female sex hormones estrogen and progesterone, and smaller amounts of the male sex hormone, testosterone. These hormones affect muscle and bone strength, sex drive, energy, and an overall sense of well being. Estrogen may also play a role in memory and mood and have a protective effect against heart disease. Women with TS have a much higher risk of developing osteoporosis (loss of bone density), high blood pressure, high cholesterol and diabetes than women without this disorder.
Girls and women with Turner syndrome between the ages of 14 and 50 years may be eligible for this 2-year study. Three months before beginning treatment, all patients will wear an estrogen patch and take a progesterone tablet daily for 10 days each month. They will then be randomly assigned to one of two treatment groups to compare the effects of estrogen alone with estrogen plus testosterone on bone strength, muscle and fat mass and psychosocial well being. Both groups will wear an estrogen patch and take oral progesterone. One group will also wear a testosterone patch while the other group will wear a placebo patch (a patch that does not contain any testosterone). Neither study participants nor the doctors will know who is getting the testosterone until the study is complete. Patients will undergo the following procedures before beginning treatment and at 6, 12 and 24 months after starting treatment:
Read more
- Physical examination.
- DEXA scans (dual energy X-ray absorptiometry) to measure body composition and bone thickness. Low radiation X-rays scan the whole body to measure fat, muscle and bone mineral content..
- Magnetic resonance imaging (MRI) scan of the abdomen to measure the amount of fat around the internal organs. The patient lies on a stretcher in a large tube surrounded by a magnetic field during the scanning. The procedure uses a strong magnet and radio waves to produce the images.
- Heel ultrasound to measure bone thickness. The heel is placed in a chamber and sound waves pass through it to produce images.
- Oral glucose tolerance test (OGTT) for diabetes and problems with carbohydrate metabolism. The patient drinks a sugary substance. A small amount of blood is drawn before taking the drink and four times afterwards.
- Blood and urine tests to measure blood counts, liver and kidney function, ovarian hormones, growth factors, thyroid function, blood lipids, bone strength markers, and to test for pregnancy.
- Blood pressure measurements.
- Psychological testing for the effect of treatment on mood, self-esteem, quality of life, social shyness, anxiety and sexual function.
- Neurocognitive tests (at first inpatient visit and 1 and 2 years after starting treatment) to measure nonverbal memory and visual-perceptual abilities.
During the hospital admissions, patients will be given a "metabolic diet" that contains specific amounts of salt and carbohydrates to ensure accurate blood pressure and sugar metabolism measurements. Patients will keep a record of their menstrual periods and physical activity throughout the treatment period.
Read the detailed description
Turner Syndrome (TS) is characterized by ovarian dysgenesis and short stature resulting from the partial or complete deletion of one X-chromosome. Adults with TS have excessive rates of osteoporosis, hypertension, dyslipidemia and diabetes mellitus and may have increased morbidity and mortality as a result. These problems of adults with TS may be secondary to deficiency of ovarian hormones or may result from halpo-insufficiency for as yet unknown X-chromosome genes. There have been no prospective, controlled studies of the effects of hormone replacement therapy (HRT) in TS, but available data suggest that conventional oral HRT designed for postmenopausal women may not prevent osteoporosis and may aggravate hypertension in this disorder. Of note, girls and women with TS are deficient in ovarian androgens as well as estrogen, and have reduced muscle mass, which may contribute to osteoporosis and insulin resistance. In addition, reduced androgens may contribute to the impairment of self esteem and social interactions suffered by many with TS. In this study, two different hormone regimens for TS will be compared in a randomized, placebo-controlled, double-blind design. Both groups will receive transdermal estradiol (E2, 100 mcg/day) with cyclic progesterone; one group will receive a physiological dose of testosterone (T) by transdermal patch while the other group will receive a placebo patch. The treatment duration is 2 years. Major outcome parameters include predicted improvements in bone mineral density, body composition and psychosocial well-being. Essential information will be collected on the effects of hormone treatments on insulin sensitivity and blood pressure in TS. This study will help to optimize hormone replacement treatment for women with TS, and to clarify which of the metabolic problems of TS are secondary to ovarian hormone deficiency, and which are due to genetic factors.
- Conditions
- Osteoporosis, Turner's Syndrome
- Being tested
- TMTDS
- Keywords
- Osteoporosis, Body Composition, Estrogen, Androgen, Ovarian Failure, Turner's Syndrome, Hormone Replacement, Turners, Turner's, TS
- Medical subject headings
- Osteoporosis, Turner Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TMTDSDrug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Mar 2001 (estimated)
- Study startMar 2001
- Study completionDec 2002
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for OsteoporosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Enrolment
- 92 participants
Sponsor and investigators
- Lead sponsor
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00013546
- Sponsor's protocol ID
- 010114
- Other IDs
- 01-CH-0114
- Status last verified
- Dec 2002
- First submitted
- 20 Mar 2001
- Last updated
- 4 Mar 2008
- Results posted
- No
Publications
Zinn AR, Ross JL. Turner syndrome and haploinsufficiency. Curr Opin Genet Dev. 1998 Jun;8(3):322-7. doi: 10.1016/s0959-437x(98)80089-0.
PubMed 9690998Lippe B. Turner syndrome. Endocrinol Metab Clin North Am. 1991 Mar;20(1):121-52.
PubMed 2029883Price WH, Clayton JF, Collyer S, De Mey R, Wilson J. Mortality ratios, life expectancy, and causes of death in patients with Turner's syndrome. J Epidemiol Community Health. 1986 Jun;40(2):97-102. doi: 10.1136/jech.40.2.97.
PubMed 3746185
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Turner Syndrome: Hormone Replacement Therapy
- ClinicalTrials.gov ID
- NCT00013546
- Acronym / sponsor ID
- 010114
- Conditions
- Osteoporosis, Turner's Syndrome
- Keywords
- Osteoporosis, Body Composition, Estrogen, Androgen, Ovarian Failure, Turner's Syndrome, Hormone Replacement, Turners
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 92 participants
- Lead sponsor
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)US National Institutes of Health
- Study start
- Mar 2001
- Study completion
- Dec 2002
- First posted
- 21 Mar 2001 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will evaluate the effects of hormone replacement therapy on patients with Turner syndrome (TS)-a genetic disorder in females in which part or all of one X chromosome is missing. Most girls and women with TS have underdeveloped ovaries-the female reproductive organs that produce the female sex hormones estrogen and progesterone, and smaller amounts of the male sex hormone, testosterone. These hormones affect muscle and bone strength, sex drive, energy, and an overall sense of well being. Estrogen may also play a role in memory and mood and have a protective effect against heart disease. Women with TS have a much higher risk of developing osteoporosis (loss of bone density), high blood pressure, high cholesterol and diabetes than women without this disorder.
Girls and women with Turner syndrome between the ages of 14 and 50 years may be eligible for this 2-year study. Three months before beginning treatment, all patients will wear an estrogen patch and take a progesterone tablet daily for 10 days each month. They will then be randomly assigned to one of two treatment groups to compare the effects of estrogen alone with estrogen plus testosterone on bone strength, muscle and fat mass and psychosocial well being. Both groups will wear an estrogen patch and take oral progesterone. One group will also wear a testosterone patch while the other group will wear a placebo patch (a patch that does not contain any testosterone). Neither study participants nor the doctors will know who is getting the testosterone until the study is complete. Patients will undergo the following procedures before beginning treatment and at 6, 12 and 24 months after starting treatment:
- Physical examination.
- DEXA scans (dual energy X-ray absorptiometry) to measure body composition and bone thickness. Low radiation X-rays scan the whole body to measure fat, muscle and bone mineral content..
- Magnetic resonance imaging (MRI) scan of the abdomen to measure the amount of fat around the internal organs. The patient lies on a stretcher in a large tube surrounded by a magnetic field during the scanning. The procedure uses a strong magnet and radio waves to produce the images.
- Heel ultrasound to measure bone thickness. The heel is placed in a chamber and sound waves pass through it to produce images.
- Oral glucose tolerance test (OGTT) for diabetes and problems with carbohydrate metabolism. The patient drinks a sugary substance. A small amount of blood is drawn before taking the drink and four times afterwards.
- Blood and urine tests to measure blood counts, liver and kidney function, ovarian hormones, growth factors, thyroid function, blood lipids, bone strength markers, and to test for pregnancy.
- Blood pressure measurements.
- Psychological testing for the effect of treatment on mood, self-esteem, quality of life, social shyness, anxiety and sexual function.
- Neurocognitive tests (at first inpatient visit and 1 and 2 years after starting treatment) to measure nonverbal memory and visual-perceptual abilities.
During the hospital admissions, patients will be given a "metabolic diet" that contains specific amounts of salt and carbohydrates to ensure accurate blood pressure and sugar metabolism measurements. Patients will keep a record of their menstrual periods and physical activity throughout the treatment period.
Detailed description
Turner Syndrome (TS) is characterized by ovarian dysgenesis and short stature resulting from the partial or complete deletion of one X-chromosome. Adults with TS have excessive rates of osteoporosis, hypertension, dyslipidemia and diabetes mellitus and may have increased morbidity and mortality as a result. These problems of adults with TS may be secondary to deficiency of ovarian hormones or may result from halpo-insufficiency for as yet unknown X-chromosome genes. There have been no prospective, controlled studies of the effects of hormone replacement therapy (HRT) in TS, but available data suggest that conventional oral HRT designed for postmenopausal women may not prevent osteoporosis and may aggravate hypertension in this disorder. Of note, girls and women with TS are deficient in ovarian androgens as well as estrogen, and have reduced muscle mass, which may contribute to osteoporosis and insulin resistance. In addition, reduced androgens may contribute to the impairment of self esteem and social interactions suffered by many with TS. In this study, two different hormone regimens for TS will be compared in a randomized, placebo-controlled, double-blind design. Both groups will receive transdermal estradiol (E2, 100 mcg/day) with cyclic progesterone; one group will receive a physiological dose of testosterone (T) by transdermal patch while the other group will receive a placebo patch. The treatment duration is 2 years. Major outcome parameters include predicted improvements in bone mineral density, body composition and psychosocial well-being. Essential information will be collected on the effects of hormone treatments on insulin sensitivity and blood pressure in TS. This study will help to optimize hormone replacement treatment for women with TS, and to clarify which of the metabolic problems of TS are secondary to ovarian hormone deficiency, and which are due to genetic factors.
Study design
- Primary purpose
- Treatment
Who may qualify
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- Girls and women with TS diagnosed by karyotype or other genetic evidence of X-chromosome defects and ovarian failure (diagnosed by failure to enter puberty spontaneously by age 18 or 2nd degree amenorrhea greater than 6 months and FSH greater than 40 mIU/ml)
- Subjects with TS who have been previously exposed to estrogen and progestin effect, either endogenous or exogenous by medical treatment, sufficient to establish secondary sexual development and menses
- Subjects with TS - ages 14 to 50, who have completed near final height, as demonstrated by a bone age of greater than or equal to 14 years
Key exclusion criteria (8 listed)
- Chronological or bone age of less than 14 years
- Chronological age greater than 50 years
- Chromosomal disorders in addition to TS
- Absence of 2nd degree sexual development
- Growth hormone or androgen treatment within 6 months of starting study.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TMTDS | Drug | – |
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Mar 2008.
- Background: PubMed 9690998Zinn AR, Ross JL. Turner syndrome and haploinsufficiency. Curr Opin Genet Dev. 1998 Jun;8(3):322-7. doi: 10.1016/s0959-437x(98)80089-0.
- Background: PubMed 2029883Lippe B. Turner syndrome. Endocrinol Metab Clin North Am. 1991 Mar;20(1):121-52.
- Background: PubMed 3746185Price WH, Clayton JF, Collyer S, De Mey R, Wilson J. Mortality ratios, life expectancy, and causes of death in patients with Turner's syndrome. J Epidemiol Community Health. 1986 Jun;40(2):97-102. doi: 10.1136/jech.40.2.97.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing TMTDS in people with Osteoporosis and Turner's Syndrome, run by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Mar 2008. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00013546, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Mar 2008.