Nordic Study on the Effects of Growth Hormone (Norditropin SimpleXx) Treatment in Adults With Prader-Willi Syndrome
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
OBJECTIVE(S):
Prader Willi syndrome (PWS) is a multi-symptomatic genetic disorder associated with abnormalities in the growth hormone (GH)-insulin-like-growth factor (IGF)-I axis and in the body composition. GH treatment is a registered indication in children with PWS, and improves growth rate and body composition. One pilot study in adult patients with clinical PWS has shown beneficial effects on body composition without simultaneous significant side effects. The aim of the present study is to evaluate the effects of GH treatment on body composition, muscle function and quality of life in PWS adults.
TRIAL DESIGN:
The study will be an investigator initiated and investigator sponsored multinational and multi-centre trial, including centres in Norway, Sweden and Denmark. Within each centre patients will be randomised (double blind) to one year treatment with daily injections of GH or placebo (efficacy), followed by a two year observation period on GH treatment (safety).
TRIAL POPULATION:
Twenty patients from each centre are included in the study. The patients need a genetically verified diagnosis and should be between 18 and 40 years old. Patients are excluded if GH treatment has been given within the last two years, if they have a malignancy or other serious diseases, in particular severe respiratory diseases.
ASSESSMENTS:
Effect is evaluated primarily as changes in body composition, activity of daily living and quality of life.
SAFETY: Before starting in the study all patients will be examined for tonsillary hypertrophy and sleep apnoea. Oral Glucose Tolerance Tests will be performed regularly.
TRIAL PRODUCT(S):
During the initial 4 weeks of the placebo-controlled study phase patients will be treated with sc injections of GH (Norditropin Simplexx) in the evening with doses of 0.3 mg/day respectively 0.4 mg/day if BW is below or above 100 kg. Thereafter doses will be increased to 0.6 mg/day (0.8 mg/day) and maintained fixed for 11 months. During the following 24 months open phase doses will be individually titrated.
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Genetically verified PWS diagnosis (by methylation and FISH test.)
- Between 18 and 50 years old
- Informed consent obtained before any trial-related activities. (Trial-related activities are any procedure that would not have been performed during normal management of the treatment of the subject.)
Exclusion Criteria:
- Known or suspected allergy to GH preparation.
- Previous participation in this trial.
- GH treatment within the last 1 years
- Malignancy or other serious diseases (ex severe cardiovascular diseases, severe infections)
- Sexhormone treatment initiated within the last year
- Pregnancy
- Untreated respiratory impairment, untreated sleep apnoea or untreated respiratory infection.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Placebo Comparator: Placebo
Placebo for 12 months
|
0.3-0.4
mg/day placebo or GH for 4 weeks.
Thereafter 0.6-0.8
mg/day placebo or GH for 11 months.
During the following 24 months open phase doses will be individually titrated.
|
|
Active Comparator: Norditropin SimpleXx
0.3 mg/day or 0.4 mg/day if bodyweight was below or above 100 kg,for 4 weeks, 0.6 mg/day or 0.8 mg/day, for 11 months.
|
0.3-0.4
mg/day placebo or GH for 4 weeks.
Thereafter 0.6-0.8
mg/day placebo or GH for 11 months.
During the following 24 months open phase doses will be individually titrated.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
|---|---|
|
Changes in body composition (lean body mass and fat mass) measured by dual energy X-ray absorptiometry (DXA)
Time Frame: 36 months
|
36 months
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
|---|---|
|
Bone mineral density measured by DXA
Time Frame: 36 months
|
36 months
|
|
Effects on forced expiratory volume (Peakflow)
Time Frame: 36 months
|
36 months
|
|
Standard photography appearance according to visual analogue scale (VAS)
Time Frame: 36 months
|
36 months
|
|
Effects on free and total IGF-I, IGF-binding protein (BP)-1 and 3
Time Frame: 36 months
|
36 months
|
|
Effects on lipids (fasting triglycerides(TG), total, HDL and LDL cholesterol)
Time Frame: 36 months
|
36 months
|
|
Effects on body composition measured with bioimpedance
Time Frame: 36 months
|
36 months
|
|
Effects on haemoglobin (Hb), leucocyte and thrombocyte counts, FSH, LH, estradiol, Testosterone, inhibin B, TSH and Thyroxine
Time Frame: 36 months
|
36 months
|
|
Muscle and fat mass measured by abdominal and mid-femoral computerized tomography
Time Frame: 36 months
|
36 months
|
|
Activity of daily living measured a.m. Guralnik
Time Frame: 36 months
|
36 months
|
|
Quality of life estimated by questionnaires
Time Frame: 36 months
|
36 months
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Charlotte Hoybye, Dr., Department of Endocrinology and Diabetology, Karolinska Hospital
- Study Chair: Jens S Christiansen, Professor, Århus University Hospital, Denmark
Publications and helpful links
General Publications
- Shukur HH, Hussain-Alkhateeb L, Farholt S, Norregaard O, Jorgensen AP, Hoybye C. Effects of Growth Hormone Treatment on Sleep-Related Parameters in Adults With Prader-Willi Syndrome. J Clin Endocrinol Metab. 2021 Aug 18;106(9):e3634-e3643. doi: 10.1210/clinem/dgab300.
- Olarescu NC, Jorgensen AP, Godang K, Jurik AG, Froslie KF, Bollerslev J. Dual-energy X-ray absorptiometry is a valid method to estimate visceral adipose tissue in adult patients with Prader-Willi syndrome during treatment with growth hormone. J Clin Endocrinol Metab. 2014 Sep;99(9):E1727-31. doi: 10.1210/jc.2014-2059. Epub 2014 Jun 23.
- Jorgensen AP, Ueland T, Sode-Carlsen R, Schreiner T, Rabben KF, Farholt S, Hoybye C, Christiansen JS, Bollerslev J. Glucose homeostasis in adults with Prader-Willi syndrome during treatment with growth hormone: results from a 12-month prospective study. Growth Horm IGF Res. 2014 Feb;24(1):16-21. doi: 10.1016/j.ghir.2013.11.002. Epub 2013 Dec 4.
- Jorgensen AP, Ueland T, Sode-Carlsen R, Schreiner T, Rabben KF, Farholt S, Hoybye C, Christiansen JS, Bollerslev J. Two years of growth hormone treatment in adults with Prader-Willi syndrome do not improve the low BMD. J Clin Endocrinol Metab. 2013 Apr;98(4):E753-60. doi: 10.1210/jc.2012-3378. Epub 2013 Feb 22.
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Nervous System Diseases
- Neurologic Manifestations
- Neurobehavioral Manifestations
- Disease
- Congenital Abnormalities
- Overnutrition
- Nutrition Disorders
- Genetic Diseases, Inborn
- Intellectual Disability
- Abnormalities, Multiple
- Chromosome Disorders
- Obesity
- Syndrome
- Prader-Willi Syndrome
Other Study ID Numbers
- CH1234
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