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Effects of Exenatide on Overweight Adolescents With Prader-Willi Syndrome

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Debra Jeandron, Children's Hospital Los Angeles
ClinicalTrials.gov Identifier:
NCT01444898
First received: September 27, 2011
Last updated: July 25, 2013
Last verified: July 2013
  Purpose

Prader-Willi Syndrome (PWS) is one of the most common genetic causes of obesity. Obesity is a major source of morbidity and mortality in this population. It can lead to sleep apnea, cor pulmonale, diabetes mellitus, and atherosclerosis. PWS has distinct characteristics that set it apart from other forms of obesity including insatiable appetite and food-seeking behavior which can be disruptive to home and school activities, and can cause severe social and psychological turmoil within families. PWS is also associated with unique hormonal abnormalities, most notably hyperghrelinemia. Ghrelin is a gut hormone produced in the stomach that stimulates food intake during a fast. It is hypothesized that the extremely high ghrelin levels in patients with PWS may cause or contribute to their insatiable appetite. Exenatide, a medication used in the treatment of type 2 diabetes mellitus in adults, appears to suppress ghrelin levels and cause weight loss. It was designed to mimic glucagon-like peptide 1 (GLP-1), an incretin hormone that stimulates insulin secretion and delays gastric emptying, among other effects. In the present study, the investigators will investigate the effects of a 6 month trial of exenatide in overweight adolescents with PWS. The investigators will quantify the changes in weight and body composition, as well as subjective measures of appetite, and concentrations of appetite-associated hormones. The investigators hypothesize that exenatide will improve weight, body composition, appetite, and plasma ghrelin levels during the treatment period.


Condition Intervention
Prader-Willi Syndrome
Drug: Exenatide

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Effects of Exenatide on Obesity and Appetite in Overweight Patients With Prader-Willi Syndrome

Resource links provided by NLM:


Further study details as provided by Children's Hospital Los Angeles:

Primary Outcome Measures:
  • Change in weight [ Time Frame: Weight at baseline, 1 month, 3 months and 6 months of treatment ] [ Designated as safety issue: No ]
  • Change in Body Mass Index (BMI) [ Time Frame: BMI at baseline, 1 month, 3 months and 6 months of treatment ] [ Designated as safety issue: No ]
  • Change in body composition [ Time Frame: Body composition at baseline and 6 months of treatment ] [ Designated as safety issue: No ]
    The investigators will measure body fat composition by whole body DEXA scan at baseline and after 6 months of treatment with exenatide.

  • Change in appetite [ Time Frame: Appetite scored at baseline, 1 month, 3 months and 6 months of treatment ] [ Designated as safety issue: No ]
    The investigators will measure appetite scores using a syndrome-validated hyperphagia questionnaire administered at all visits except for the screening visit.


Secondary Outcome Measures:
  • Change in fasting and post-prandial levels of obesity-related hormones [ Time Frame: Levels will be measured at baseline, 1 month, 3 months, and 6 months of treatment. ] [ Designated as safety issue: No ]
    The investigators will measure serum fasting and post-prandial levels of obesity-realated hormones (ghrelin, peptide tyrosine tyrosine [PYY], pancreatic polypeptide [PP], leptin, glucose, and insulin) over a 6-month course of exenatide. The investigators will measure fasting and post-prandial serum/plasma levels of these analytes during a standardized mixed meal tolerance test (MMTT) prior to and then after 6 months of treatment. The investigators will also monitor fasting levels of these analytes after 1 and 3 months of treatment


Estimated Enrollment: 20
Study Start Date: March 2012
Estimated Study Completion Date: December 2013
Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Exenatide
All subjects enrolled in this study will be given Exenatide for 6 months.
Drug: Exenatide
The investigators will give patients naive to GLP-1 agonists exenatide per manufacturer dosing recommendations for 6 months. The investigators will begin by giving 5 mcg subcutaneously twice a day for 1 month and then increase the dose to 10 mcg subcutaneously twice a day for the remainder of the study (5 months).
Other Name: Byetta

  Eligibility

Ages Eligible for Study:   13 Years to 20 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of Prader Willi Syndrome confirmed by genetic testing (DNA methylation or FISH)
  • Ages 13-20 years
  • body mass index (BMI) > 85th percentile for age and gender

Exclusion Criteria:

  • Is currently using or has previously used a glucagon-like peptide-1 (GLP-1) agonist
  • History of pancreatitis, or renal failure
  • History of familial pancreatitis
  • Amylase, or lipase levels > 2.5 times the upper limit of normal any time in the previous 2 years
  • Creatinine clearance < 30 mL/min
  • Other syndromic diagnoses
  • gastrointestinal (GI) or renal illness in the 1 month prior to entering study
  • Inability to take study drug
  • Pregnancy
  • Initiation of growth hormone (GH), estrogen, or testosterone or change > 25% of dose/kg/day during the 6 months prior to starting study
  • Non-English speaking
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01444898

Locations
United States, California
Children's Hospital of Los Angeles
Los Angeles, California, United States, 90027
Sponsors and Collaborators
Children's Hospital Los Angeles
Investigators
Principal Investigator: Debra Jeandron, MD Children's Hospital Los Angeles
  More Information

Publications:

Responsible Party: Debra Jeandron, Principal Investigator, Children's Hospital Los Angeles
ClinicalTrials.gov Identifier: NCT01444898     History of Changes
Other Study ID Numbers: CCI 11-00227
Study First Received: September 27, 2011
Last Updated: July 25, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Children's Hospital Los Angeles:
Prader-Willi Syndrome
Obesity
Weight
Exenatide
Byetta
Pediatrics
Adolescents

Additional relevant MeSH terms:
Prader-Willi Syndrome
Overweight
Syndrome
Abnormalities, Multiple
Body Weight
Chromosome Disorders
Congenital Abnormalities
Disease
Genetic Diseases, Inborn
Intellectual Disability
Nervous System Diseases
Neurobehavioral Manifestations
Neurologic Manifestations
Nutrition Disorders
Obesity
Overnutrition
Pathologic Processes
Signs and Symptoms
Exenatide
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Hypoglycemic Agents
Incretins
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on November 20, 2014