Effect of Rimonabant on Weight Gain and Body Composition in Adults With Prader Willi Syndrome (PWS)

Effect of Rimonabant, a Cannabinoid Receptor 1 Antagonist on Weight Gain and Body Composition in Adults With Prader Willi Syndrome.

The purpose of this study is to evaluate the effect of rimonabant, a cannabinoid receptor-1 blocking drug, on the appetite, body weight, body fat and growth hormone level of subjects with Prader-Willi Syndrome (PWS). This will be a double blind placebo controlled clinical trial involving a total of 18 young adults aged 18 to 35 years with PWS. Patients will be divided in to the two groups of control and intervention, and treated with either placebo (inactive drug), or rimonabant 20 mg once a day for a total duration of 6 months. Body weight, fat distribution, objective and subjective assessment of the hunger, fasting blood sample for measurement of ghrelin and leptin (two hormones regulating appetite), serum lipids , IGF-1(growth hormone related protein), insulin and glucose concentrations will be measured upon enrollment, at 3 months, and at the end of the study. The proportion of body fat to muscle will be determined using a radiological technique, whole body dual-energy x-ray absorptiometry (DEXA) scan, and also by measurement of skin fold thickness, waist and hip circumference at the enrollment prior to the intervention, and at the end of the study.

Study Overview

• Status: Terminated
• Conditions: Prader-willi Syndrome
• Intervention / Treatment: Drug: rimonabant; Drug: placebo

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Roja Motaghedi, MD; Phone Number: 212-746-3462; Email: rom9027@med.cornell.edu
• Study Contact Backup: Name: Moris Angulo, MD; Phone Number: 516-663-3090; Email: MAngulo@Winthrop.org

Study Locations

• United States
  • New York
    • New York, New York, United States, 10065
      • New York Presbyterian Hospital-Weill Cornell Medical College

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 35 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Subjects will be selected if they have Prader Willi Syndrome previously confirmed by standard genetic testing (the DNA methylation test) or meet the clinical diagnostic criteria as follows :the presence of at least four of the six principal characteristics of PWS syndrome including 1) infantile hypotonia, 2) abnormal pubertal development, 3) obesity after early infancy, 4) dysfunctional central nervous system performance, 5) dysmorphic facial features, and 6) short stature. In addition, they must have one or more of the following characteristics commonly associated with PWS: 1) small hands and feet, 2) skin problems, 3) behavioral problems related to food, and 4) decreased pain sensitivity.
2. Subjects must be 18 to 35 years of age and fairly cooperative with the study protocol.
3. Subjects must have a BMI of at least 30 or more.

Exclusion Criteria:

1. Presence of pulmonary disease.
2. Presence of any other abnormal endocrine findings, including abnormal thyroid function.
3. Presence of significant behavioral problems or psychiatric illness including anxiety disorder and depression, interfering with the follow up of protocol. Any degree of depression and moderate to severe anxiety will be exclusion criteria for this study.
4. Subjects with Prader Willi Syndrome who are on other medications including growth hormone therapy, anti epileptic medications, or antipsychotic medications.
5. The presence of moderate to severe renal or liver disease. Mild elevations of liver enzymes are not exclusive.
6. Subjects who are on any other research or weight loss medication

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: I; Subjects receive rimonabant 20 mg per day PO	Drug: rimonabant; rimonabant capsule 20 mg per day PO for 6 months; Other Names: Acomplia
Placebo Comparator: II; Subjects take placebo capsule one a day PO	Drug: placebo; Subjects take 20 mg placebo capsule one a day PO for 6 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Body Weight and Body fat mass	6 months

Secondary Outcome Measures

Outcome Measure	Time Frame
IGF-1, Leptin, Ghrelin, Serum Lipids and insulin sensitivity	6 months

Collaborators and Investigators

• Sponsor: Weill Medical College of Cornell University
• Collaborators: National Institutes of Health (NIH); PWSAUSA
• Investigators: Principal Investigator: Roja Motaghedi, MD, NYPH-Weill Cornell Medical College; Principal Investigator: Moris Angulo, MD, Winthrop University Hospital

Publications and helpful links

General Publications

• Deal CL, Tony M, Hoybye C, Allen DB, Tauber M, Christiansen JS; 2011 Growth Hormone in Prader-Willi Syndrome Clinical Care Guidelines Workshop Participants. GrowthHormone Research Society workshop summary: consensus guidelines for recombinant human growth hormone therapy in Prader-Willi syndrome. J Clin Endocrinol Metab. 2013 Jun;98(6):E1072-87. doi: 10.1210/jc.2012-3888. Epub 2013 Mar 29.
• Motaghedi R, Lipman EG, Hogg JE, Christos PJ, Vogiatzi MG, Angulo MA. Psychiatric adverse effects of rimonobant in adults with Prader Willi syndrome. Eur J Med Genet. 2011 Jan-Feb;54(1):14-8. doi: 10.1016/j.ejmg.2010.09.015. Epub 2010 Oct 20.

Study record dates

Study Major Dates

• Study Start: August 1, 2007
• Primary Completion (Actual): January 1, 2009
• Study Completion (Actual): January 1, 2009

Study Registration Dates

• First Submitted: January 15, 2008
• First Submitted That Met QC Criteria: January 26, 2008
• First Posted (Estimate): January 28, 2008

Study Record Updates

• Last Update Posted (Actual): March 20, 2023
• Last Update Submitted That Met QC Criteria: March 16, 2023
• Last Verified: March 1, 2016

More Information

Terms related to this study

• Keywords: Body weight, fat mass, growth hormone, ghrelin
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Disease; Congenital Abnormalities; Overnutrition; Nutrition Disorders; Body Weight; Genetic Diseases, Inborn; Body Weight Changes; Intellectual Disability; Abnormalities, Multiple; Chromosome Disorders; Obesity; Syndrome; Weight Gain; Prader-Willi Syndrome; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Anti-Obesity Agents; Cannabinoid Receptor Modulators; Cannabinoid Receptor Antagonists; Rimonabant
• Other Study ID Numbers: 0611008841

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO