- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01444898
Effects of Exenatide on Overweight Adolescents With Prader-Willi Syndrome
Effects of Exenatide on Obesity and Appetite in Overweight Patients With Prader-Willi Syndrome
Study Overview
Detailed Description
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.
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
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California
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Los Angeles, California, United States, 90027
- Children's Hospital of Los Angeles
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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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).
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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 Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in Weight
Time Frame: 6 months
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Change in weight (kg) after 6 months of treatment with study drug.
Described as mean +/- SD
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6 months
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% Change in Body Mass Index (BMI)
Time Frame: 6 months
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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.
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6 months
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Change in BMI Z-Score
Time Frame: 6 months
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6 months
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Change in HbA1c (%)
Time Frame: 6 months
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6 months
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Change in Insulin Levels
Time Frame: 6 months
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6 months
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Change in Leptin
Time Frame: 6 months
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6 months
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Change in Acy Ghr
Time Frame: 6 months
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6 months
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Change in Pancreatic Peptide (PP)
Time Frame: 6 months
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6 months
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Appetite Scores
Time Frame: 6 months
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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 |
6 months
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Debra Jeandron, MD, Children's Hospital Los Angeles
Publications and helpful links
General Publications
- Suzuki K, Simpson KA, Minnion JS, Shillito JC, Bloom SR. The role of gut hormones and the hypothalamus in appetite regulation. Endocr J. 2010;57(5):359-72. doi: 10.1507/endocrj.k10e-077. Epub 2010 Apr 14.
- Rosenstock J, Klaff LJ, Schwartz S, Northrup J, Holcombe JH, Wilhelm K, Trautmann M. Effects of exenatide and lifestyle modification on body weight and glucose tolerance in obese subjects with and without pre-diabetes. Diabetes Care. 2010 Jun;33(6):1173-5. doi: 10.2337/dc09-1203. Epub 2010 Mar 23.
- Goldstone AP. The hypothalamus, hormones, and hunger: alterations in human obesity and illness. Prog Brain Res. 2006;153:57-73. doi: 10.1016/S0079-6123(06)53003-1.
- Goldstone AP. Prader-Willi syndrome: advances in genetics, pathophysiology and treatment. Trends Endocrinol Metab. 2004 Jan-Feb;15(1):12-20. doi: 10.1016/j.tem.2003.11.003.
- Wren AM, Seal LJ, Cohen MA, Brynes AE, Frost GS, Murphy KG, Dhillo WS, Ghatei MA, Bloom SR. Ghrelin enhances appetite and increases food intake in humans. J Clin Endocrinol Metab. 2001 Dec;86(12):5992. doi: 10.1210/jcem.86.12.8111.
- Cummings DE, Clement K, Purnell JQ, Vaisse C, Foster KE, Frayo RS, Schwartz MW, Basdevant A, Weigle DS. Elevated plasma ghrelin levels in Prader Willi syndrome. Nat Med. 2002 Jul;8(7):643-4. doi: 10.1038/nm0702-643. No abstract available.
- Paik KH, Jin DK, Song SY, Lee JE, Ko SH, Song SM, Kim JS, Oh YJ, Kim SW, Lee SH, Kim SH, Kwon EK, Choe YH. Correlation between fasting plasma ghrelin levels and age, body mass index (BMI), BMI percentiles, and 24-hour plasma ghrelin profiles in Prader-Willi syndrome. J Clin Endocrinol Metab. 2004 Aug;89(8):3885-9. doi: 10.1210/jc.2003-032137.
- Perez-Tilve D, Gonzalez-Matias L, Alvarez-Crespo M, Leiras R, Tovar S, Dieguez C, Mallo F. Exendin-4 potently decreases ghrelin levels in fasting rats. Diabetes. 2007 Jan;56(1):143-51. doi: 10.2337/db05-0996.
- Seetho IW, Jones G, Thomson GA, Fernando DJ. Treating diabetes mellitus in Prader-Willi syndrome with Exenatide. Diabetes Res Clin Pract. 2011 Apr;92(1):e1-2. doi: 10.1016/j.diabres.2010.12.009. Epub 2011 Jan 11.
- Salehi P, Hsu I, Azen CG, Mittelman SD, Geffner ME, Jeandron D. Effects of exenatide on weight and appetite in overweight adolescents and young adults with Prader-Willi syndrome. Pediatr Obes. 2017 Jun;12(3):221-228. doi: 10.1111/ijpo.12131. Epub 2016 Apr 13.
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Nervous System Diseases
- Neurologic Manifestations
- Neurobehavioral Manifestations
- Disease
- Congenital Abnormalities
- Overnutrition
- Nutrition Disorders
- Body Weight
- Genetic Diseases, Inborn
- Intellectual Disability
- Abnormalities, Multiple
- Chromosome Disorders
- Obesity
- Syndrome
- Overweight
- Prader-Willi Syndrome
- Hypoglycemic Agents
- Physiological Effects of Drugs
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Anti-Obesity Agents
- Incretins
- Exenatide
Other Study ID Numbers
- CCI 11-00227
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
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