GH in Adults With PWS, Effect on Hypotonia Evaluated by Functional MRI, Relationship With Strength and Body Composition

Study Overview
=================
Brief Summary
-----------------
Prader-Willi syndrome (PWS) is a genetic disorder associated with growth hormone (GH) deficiency, central hypotonia and hyperphagia that leads to life-threatening obesity. Treatment with GH in adult patients is not well stablished in guidelines of Health National System (HNS). The investigators has experience in the study of brain connectivity in these patients in relation to satiety. To date, there is no evidence about the effect of GH on central hypotonia (brain areas related with muscle tone maintenance). So, the main objective is to examine these anatomical areas before and one year after GH treatment. Methodology: Structural and functional magnetic resonance imaging to 30 PWS patients before and after GH treatment and we will compare them to a control group. Expected results: PWS group will show abnormal functional and structural connectivity in circuitry of muscle tone maintenance that will improve after GH treatment. These favorable changes and the absence of secondary effects will help to justify the use of this treatment and its inclusion in practical clinical guidelines of HNS for the management of this syndrome in the adulthood.

Official Title
-----------------
Treatment With Growth Hormone in Adults With PWS, Effect on Muscular Tone Evaluated by Functional MRI, Relationship With Strength and Body Composition

Conditions
-----------------
Prader-Willi Syndrome

Intervention / Treatment
-----------------
* Drug: Growth hormone
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: PWS >=18 years with growth hormone deficit Signed informed consent by the patients or their legal guardian Exclusion Criteria: Severe obesity No controled diabetes mellitus No treated obstructive sleep apnea or severe obstructive sleep apnea Active cancer Active psychosis

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: First phase: 2m with placebo Second phase: 12 m with growth hormone
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Placebo and Growth Hormone<br>2 months on placebo followed by 12 months on GH | Drug: Growth hormone<br>* 12 months on Growth hormone, initial dose 0,2 mg per day, then adjusted by insulin like growth factor (IGF-1) level<br>* Other names: Genotonorm Miniquick;Drug: Placebo<br>* 2 months on placebo, sodium chloride 0,9% injections<br>* Other names: Physiological serum (sodium chloride 0,9%);|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Examine brain connectivity areas related with muscle tone maintenance | Examine brain connectivity areas related with muscle tone maintenance making a functional MRI while the subject is making motor maneuvers, before anf after 12 months on GH treatment. | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of strength | Evaluation of strength before and after 12 months on GH treatment | 24 months | 
| Evaluation of body composition | Evaluation of body composition by Dual energy x-ray absorptiometry (DEXA) before and after 12 months on GH treatment | 24 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Growth Hormone, Functional Magnetic Resonance, Strength, Body composition