Nordic Study on the Effects of Growth Hormone (Norditropin SimpleXx) Treatment in Adults With Prader-Willi Syndrome

Study Overview
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Brief Summary
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The aim of this study is to study the effects of GH on body composition, lipid and glucose metabolism, physical performance and safety aspects in adults with PWS.The patients are randomized to either GH or placebo the first year of the study, subsequently followed by two years of GH treatment. the study is performed in Norway, Sweden and Denmark.

Detailed Description
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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.

Official Title
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Nordic Study on the Effects of Growth Hormone (Norditropin SimpleXx) Treatment in Adults With Prader-Willi Syndrome

Conditions
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Prader-Willi Syndrome

Intervention / Treatment
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* Drug: Norditropin SimpleXx


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Norditropin SimpleXx<br>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. | Drug: Norditropin SimpleXx<br>* 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.<br>|
| Placebo Comparator: Placebo<br>Placebo for 12 months | Drug: Norditropin SimpleXx<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in body composition (lean body mass and fat mass) measured by dual energy X-ray absorptiometry (DXA) |  | 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bone mineral density measured by DXA |  | 36 months | 
| Effects on forced expiratory volume (Peakflow) |  | 36 months | 
| Standard photography appearance according to visual analogue scale (VAS) |  | 36 months | 
| Effects on free and total IGF-I, IGF-binding protein (BP)-1 and 3 |  | 36 months | 
| Effects on lipids (fasting triglycerides(TG), total, HDL and LDL cholesterol) |  | 36 months | 
| Effects on body composition measured with bioimpedance |  | 36 months | 
| Effects on haemoglobin (Hb), leucocyte and thrombocyte counts, FSH, LH, estradiol, Testosterone, inhibin B, TSH and Thyroxine |  | 36 months | 
| Muscle and fat mass measured by abdominal and mid-femoral computerized tomography |  | 36 months | 
| Activity of daily living measured a.m. Guralnik |  | 36 months | 
| Quality of life estimated by questionnaires |  | 36 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Prader-Willi syndrome, Growth hormone, Body composition