GGAP: Global Growth Hormone Study in Adults With Prader-Willi Syndrome
Study Details
Study Description
Brief Summary
The overall objective of this study is to measure the effect of growth hormone treatment on physical and psychosocial health in adults of 30 years or older with Prader-Willi syndrome. Patients are randomized to placebo or growth hormone treatment during the first year. They will switch treatment during the second year, so that each participant receives one year of growth hormone treatment and one year of placebo (cross-over study). We hypothesize that growth hormone treatment will improve the physical and psychosocial health.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Detailed Description
OBJECTIVES:
The overall objective is to measure the effect of growth hormone treatment (GHt) on physical and psychosocial health in adults of 30 years or older with Prader-Willi syndrome (PWS).
The primary objective is to measure the effect of GHt on lean body mass as measured by Dual Energy X-ray Absorptiometry scan in adults of 30 years or older with PWS.
The secondary objective is to measure the effect of GHt on total fat mass, bone density, physical health cardiovascular fitness, laboratory measurements, muscle strength, endurance, and psychosocial functioning in adults of 30 years or older with PWS. Also the occurrence of side-effects will be assessed.
STUDY DESIGN:
Randomized, double-blinded, placebo controlled crossover trial for two years with a washout period of 3 months.
STUDY POPULATION:
50 adults with PWS of 30 years or older who have not been treated with GH during the past three years.
INTERVENTION:
subcutaneous injections of growth hormone (Genotropin, 5.0 mg/mL) in a dosage of 0.6 - 0.8 mg/day. The comparator is placebo.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Active comparator: Genotropin Subcutaneous injections Genotropin, 0.6-0.8 mg/day. Participants start with 0.2 mg/day and the dose increases with 0.2 mg/day per month to a maximum dose of 0.6-0.8 mg/day. |
Drug: Somatropin
The intervention is growth hormone treatment (Genotropin), 0.6 - 0.8 mg/day subcutaneous for one year. It is an intramural medicament with an add-on. Participants start with 0.2 mg/day. The growth hormone dose increases with 0.2 mg/day per month to a maximum dose of 0.6 - 0.8 mg/day based on clinical signs (occurrence of side-effects)
Other Names:
|
| Placebo Comparator: Placebo comparator: Placebo Placebo for 12 months. |
Drug: Placebo
The comparator is placebo, 0.6 - 0.8 mg/day subcutaneous for one year. Participants start with 0.2 mg/day. The dose increases with 0.2 mg/day per month to a maximum dose of 0.6 - 0.8 mg/day.
|
Outcome Measures
Primary Outcome Measures
- Change in lean body mass [27 months]
Change in lean body mass (in kg) as measured by Dual Energy X-ray Absorptiometry scan
Secondary Outcome Measures
- Change in fat mass [27 months]
Change in fat mass (in kg) as measured by Dual Energy X-ray Absorptiometry scan
- Change in bone density [27 months]
Change in bone density (in T-score) as measured by Dual Energy X-ray Absorptiometry scan
- Change in cardiovascular fitness [27 months]
Change in cardiovascular fitness as estimated with an ECG during the treadmill stress test. We look for axis devations in LEAD I and aVF. We also look for signs of ischemia (ST depression, T wave inversion and pathologic Q waves).
- Change in laboratory measurements [27 months]
Changes in the following laboratory measurements: Fasting blood glucose (mmol/L) Glycosylated hemoglobin (mmol/mol) Total cholesterol (mmol/L) Low-density lipoprotein cholesterol (mmol/L) High-density lipoprotein cholesterol (mmol/L) Triglycerides (mmol/L) Insulin-like growth factor 1 (nmol/L) Free thyroxine 4 (pmol/L) Luteinizing hormone (U/I) Follicle stimulating hormone (U/I) Estradiol or testosterone (nmol/L) Sex hormone binding globulin (nmol/L) Aspartate transaminase (U/L) Alanine transaminase (U/L) Alkaline phosphatase (U/L) Gamma glutamyl transpeptidase (U/L) Total bilirubin (micromol/L) Lactate dehydrogenase (U/L) Urea (mmol/L) Creatinine (micromol/L) Hemoglobin (mmol/L) Hematocrit (L/L) Mean corpuscular volume (fL) Leukocytes (10^9/L) Thrombocytes (10^9/L) 25-OH vitamin D (nmol/L)
- Change in muscle strength [27 months]
Change in muscle strength as determined with a handgrip dynamometer
- Change in endurance [27 months]
Change in endurance as estimated with the treadmill stress test
- Change in psychosocial functioning [27 months]
Change in psychosocial functioning as estimated with the Adult Behaviour Checklist
Other Outcome Measures
- Change in weight and waist-hip ratio [27 months]
Change in weight (in kg) and waist-hip ratio
- Change in blood pressure [27 months]
Change in blood pressure (in mmHg)
- Occurence of side-effects [27 months]
Occurrence of side-effects
Eligibility Criteria
Criteria
Inclusion Criteria:
-
The patient is diagnosed with Prader-Willi syndrome (genetically confirmed)
-
The patient is 30 years or older
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In case of previous GH treatment (for example in trial setting), GH should be stopped at least three years before starting the study
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The patient is treated by a dietitian (caloric restriction) for at least three months
Exclusion Criteria:
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Non cooperative behaviour
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Pregnancy
-
Known malignancies
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Poorly controlled diabetes (HbA1c > 64 mmol/mol (8%))
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Untreated obstructive sleep apnea (apnea-hypopnea index > 5)
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Body mass index above 40 kg/m2
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Upper-airway obstruction of any cause
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Change in testosterone or estrogen replacement therapy in the last three months prior to study
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Royal Prince Alfred Hospital | Camperdown | Australia | NSW 2050 | |
| 2 | Erasmus MC, University Medical Center Rotterdam | Rotterdam | Zuid-Holland | Netherlands | 3015GD |
Sponsors and Collaborators
- Erasmus Medical Center
- Pfizer
- Foundation for Prader-Willi Research
- Prader-Willi Fonds
Investigators
- Principal Investigator: Laura de Graaff, MD, PhD, Erasmus MC, University Medical Center Rotterdam
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- GGAP