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Effects of Exenatide on Overweight Adolescents With Prader-Willi Syndrome

This study has been completed.
Information provided by (Responsible Party):
Mitchell E. Geffner, Children's Hospital Los Angeles Identifier:
First received: September 27, 2011
Last updated: September 27, 2016
Last verified: September 2016
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: 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: 6 months ] [ Designated as safety issue: No ]
    Change in weight (kg) after 6 months of treatment with study drug. Described as mean +/- SD

  • % Change in Body Mass Index (BMI) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Prior to analysis, distributions were evaluated for normality and natural log transformation was performed to analyse data not normally distributed. Data are presented as mean ±SD unless not normally distributed, in which case they are presented as median with intra-quartile ranges (25th and 75th percentiles). Within-subject changes between visits were analysed by mixed model repeated measures. When the overall F-test for difference among visits was significant, Dunnett-adjusted pairwise comparisons were made between baseline and each subsequent visit.

  • Change in BMI Z-Score [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Change in HbA1c (%) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Change in Insulin Levels [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Change in Leptin [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Change in Acy Ghr [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Change in Pancreatic Peptide (PP) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Appetite Scores [ Time Frame: 6 months ] [ Designated as safety issue: No ]

    Appetite scores using a syndrome-validated hyperphagia questionnaire

    11 item questionnaire divided into subcategories of behavior (5 questions), drive (4 questions), severity (2 questions). Tallied and analyzed as total and subcategory scores. Each question scored 1-5 with higher scores correlating with worse hyperphagia.

    Possible ranges: Total 11-55, behavior 5-25, drive 4-20, severity 2-10

Enrollment: 10
Study Start Date: March 2012
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. 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).
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

Detailed Description:


Prader-Willi syndrome (PWS) is associated with hyperphagia and hyperghrelinemia with major morbidity because of obesity without effective medical treatment targeting hyperphagia. Exenatide (Byetta [synthetic Exendin-4]; AstraZeneca, Wilmington DE) is a GLP-1 receptor agonist which reduces appetite and weight and may be an effective treatment in PWS.

OBJECTIVE: The objective of this study is to determine the effect of a 6-month trial of exenatide on appetite, weight and gut hormones in youth with PWS.


Ages Eligible for Study:   13 Years to 20 Years   (Child, Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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
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Please refer to this study by its identifier: NCT01444898

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


Responsible Party: Mitchell E. Geffner, Principal Investigator, Children's Hospital Los Angeles Identifier: NCT01444898     History of Changes
Other Study ID Numbers: CCI 11-00227 
Study First Received: September 27, 2011
Results First Received: June 14, 2016
Last Updated: September 27, 2016
Health Authority: United States: Institutional Review Board
Individual Participant Data  
Plan to Share IPD: Undecided

Keywords provided by Children's Hospital Los Angeles:
Prader-Willi Syndrome

Additional relevant MeSH terms:
Body Weight
Prader-Willi Syndrome
Pathologic Processes
Signs and Symptoms
Intellectual Disability
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Abnormalities, Multiple
Congenital Abnormalities
Chromosome Disorders
Genetic Diseases, Inborn
Nutrition Disorders
Hypoglycemic Agents
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists processed this record on October 26, 2016