The aim of the study is to assess the long-term effects (at adult age) of the TOS study medication (growth hormone and estrogen with or without Ox), with specific attention to adult height and body proportions, body composition, virilization,…
ID
Source
Brief title
Condition
- Endocrine disorders congenital
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The main study parameters are: height, body proportions, body composition,
symptoms and signs of virilization, glucose tolerance, lipid profile, cardiac
conduction abnormalities, liver and thyroid function, (neuro)psychological
function and quality of life. The effects of Ox are analyzed to a background of
genotypic variation of the sex chromosomes and the growth hormone receptor.
Secondary outcome
Not applicable
Background summary
Turner syndrome is the result of complete or partial absence of one
X-chromosome. Besides short stature and gonadal dysgenesis, Turner syndrome is
associated with a wide range of abnormalities affecting nearly every organ
system. In 1991 the Dutch multicentre Turner Oxandrolone Study (TOS) started: a
randomized double-blind placebo controlled study on the effect of the androgen
oxandrolone (Ox) in combination with authentic biosynthetic human growth
hormone and low-dose estrogens on growth and metabolic parameters in girls with
Turner syndrome (CEOM-nr 9202-0029). In TOS, the girls were followed until a
mean of 1.5 years after cessation of growth hormone and Ox/placebo. Preliminary
analysis suggests that Ox enhances growth at cost of mild virilization and
deceleration of breast development, especially in the high-dose group. The
beneficial and possible adverse effects of Ox potentially carry on into
adulthood, i.e. far beyond the scope of the original pediatric study. The
present study represents a long term follow-up of TOS. The girls who
participated in the original TOS have now reached an adult age.
Study objective
The aim of the study is to assess the long-term effects (at adult age) of the
TOS study medication (growth hormone and estrogen with or without Ox), with
specific attention to adult height and body proportions, body composition,
virilization, metabolic cardiovascular risk profile, neuropsychological
function and quality of life. Our hypothesis, is that permanent beneficial
effects of auxiliary treatment with Ox outweigh short-lived adverse effects.
Study design
This is an observational study and represents the long-term follow-up of a
multicentre double-blind placebo controlled trial.
Study burden and risks
Participating subjects are investigated during a single, whole-day visit to the
RUNMC which comprises of standardized history taking and physical examination
including standardized photographs, sampling of blood, urine, hair and buccal
mucosa, (neuro)psychological investigations, voice frequency analysis and
audiometry, bone mineral density and body composition measurement and
electrocardiography. The risks associated with these investigations for the
participants are minimal. If the investigations yield abnormalities relevant to
the patient, the patient will be referred to their own physician for adequate
treatment.
Postbus 9101
6500 HB Nijmegen
NL
Postbus 9101
6500 HB Nijmegen
NL
Listed location countries
Age
Inclusion criteria
Inclusion criteria are completion of the original TOS protocol at least 6 months prior to the study visit and age >=18 years. Main inclusion criteria of the original protocol (TOS) were: a) the diagnosis of TS should be confirmed by lymphocyte chromosomal analysis. Any chromosomal pattern which is known to be associated with TS characteristics is acceptable, except for evidence of a Y-chromosome on blood analysis. b) Chronological age between 2 and 15.99 years. c) Well-documented growth rate during the previous year. d) Bone-age lower than 12.0 years.
Exclusion criteria
Exclusion criteria are: a) Patients who have participated in another experimental drug study within two months of entry into the present study. b) Malignant or severely disabling disease. c) Serious suspicion of psychiatric illnesses. d) Pregnancy or current fertility treatment.
Main exclusion criteria of the original protocol: a) Any endocrine or metabolic disorder, with the exception of thyroidal illnesses adequately treated and/or substituted. b) Growth failure due to disorders of urinary, cardiopulmonary, gastro-intestinal and nervous systems; nutritional/vitamin deficiencies and chondrodysplasias. c) Patients with hydrocephalus. d) Patients who have participated in another experimental drug study within two months of entry. e) Patients receiving any kind of drug that may interfere with GH therapy. f) Previous GH, sex hormone, or anabolic steroid treatment. g) Presence of any persistent abnormality at general pediatric and biochemical screening (including scoliosis, liver function tests, kidney function tests, electrtolytes, blood count, urine glucose, protein and sediment). h) Serious suspicion of psychosocial dwarfism (emotional deprivation) or psychiatric illnesses.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL26203.091.09 |