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Effects of Exenatide on Overweight Adolescents With Prader-Willi Syndrome

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01444898
Recruitment Status : Completed
First Posted : October 3, 2011
Results First Posted : September 29, 2016
Last Update Posted : September 29, 2016
Information provided by (Responsible Party):
Mitchell E. Geffner, Children's Hospital Los Angeles

Brief Summary:
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 or disease Intervention/treatment Phase
Prader-Willi Syndrome Drug: Exenatide Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 10 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Effects of Exenatide on Obesity and Appetite in Overweight Patients With Prader-Willi Syndrome
Study Start Date : March 2012
Actual Primary Completion Date : May 2013
Actual Study Completion Date : December 2013

Resource links provided by the National Library of Medicine

Drug Information available for: Exenatide

Arm Intervention/treatment
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

Primary Outcome Measures :
  1. Change in Weight [ Time Frame: 6 months ]
    Change in weight (kg) after 6 months of treatment with study drug. Described as mean +/- SD

  2. % Change in Body Mass Index (BMI) [ Time Frame: 6 months ]
    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.

  3. Change in BMI Z-Score [ Time Frame: 6 months ]
  4. Change in HbA1c (%) [ Time Frame: 6 months ]
  5. Change in Insulin Levels [ Time Frame: 6 months ]
  6. Change in Leptin [ Time Frame: 6 months ]
  7. Change in Acy Ghr [ Time Frame: 6 months ]
  8. Change in Pancreatic Peptide (PP) [ Time Frame: 6 months ]
  9. Appetite Scores [ Time Frame: 6 months ]

    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

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Ages Eligible for Study:   13 Years to 20 Years   (Child, Adult)
Sexes Eligible for Study:   All
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01444898

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

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Responsible Party: Mitchell E. Geffner, Principal Investigator, Children's Hospital Los Angeles Identifier: NCT01444898    
Other Study ID Numbers: CCI 11-00227
First Posted: October 3, 2011    Key Record Dates
Results First Posted: September 29, 2016
Last Update Posted: September 29, 2016
Last Verified: September 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Keywords provided by Mitchell E. Geffner, Children's Hospital Los Angeles:
Prader-Willi Syndrome
Additional relevant MeSH terms:
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Prader-Willi Syndrome
Pathologic Processes
Body Weight
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
Anti-Obesity Agents
Hormones, Hormone Substitutes, and Hormone Antagonists