Clinical Trial: Effects of Exenatide on Overweight Adolescents With Prader-Willi Syndrome

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Effects of Exenatide on Obesity and Appetite in Overweight Patients With Prader-Willi Syndrome

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.

Detailed Summary:

BACKGROUND:

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.


Sponsor: Children's Hospital Los Angeles

Current Primary Outcome:

  • Change in Weight [ Time Frame: 6 months ]
    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 ]
    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 ]
  • Change in HbA1c (%) [ Time Frame: 6 months ]
  • Change in Insulin Levels [ Time Frame: 6 months ]
  • Change in Leptin [ Time Frame: 6 months ]
  • Change in Acy Ghr [ Time Frame: 6 months ]
  • Change in Pancreatic Peptide (PP) [ Time Frame: 6 months ]
  • 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

    Original Primary Outcome:

    • Change in weight [ Time Frame: Weight at baseline, 1 month, 3 months and 6 months of treatment ]
    • Change in Body Mass Index (BMI) [ Time Frame: BMI at baseline, 1 month, 3 months and 6 months of treatment ]
    • Change in body composition [ Time Frame: Body composition at baseline and 6 months of treatment ]
      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 ]
      The investigators will measure appetite scores using a syndrome-validated hyperphagia questionnaire administered at all visits except for the screening visit.


    Current Secondary Outcome:

    Original Secondary Outcome: 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. ]

    The investigators will measure serum fasting and post-prandial levels of obesity-realated hormones (ghrelin, PYY, 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 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


    Information By: Children's Hospital Los Angeles

    Dates:
    Date Received: September 27, 2011
    Date Started: March 2012
    Date Completion:
    Last Updated: September 27, 2016
    Last Verified: September 2016