Effects of Exenatide on Overweight Adolescents With Prader-Willi Syndrome

Condition(s) targeted: Prader-Willi Syndrome

Intervention: Exenatide (Drug)

Phase: N/A

Status: Active, not recruiting

Sponsored by: Children's Hospital Los Angeles

Official(s) and/or principal investigator(s):
Debra Jeandron, MD, Principal Investigator, Affiliation: Children's Hospital Los Angeles

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.

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

Study design: Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome:

Change in weight

Change in Body Mass Index (BMI)

Change in body composition

Change in appetite

Secondary outcome: Change in fasting and post-prandial levels of obesity-related hormones

Minimum age: 13 Years. Maximum age: 20 Years. Gender(s): Both.

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

Children's Hospital of Los Angeles, Los Angeles, California 90027, United States

Related publications:

Goldstone AP. The hypothalamus, hormones, and hunger: alterations in human obesity and illness. Prog Brain Res. 2006;153:57-73. Review.

Goldstone AP. Prader-Willi syndrome: advances in genetics, pathophysiology and treatment. Trends Endocrinol Metab. 2004 Jan-Feb;15(1):12-20. Review.

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. Epub 2010 Apr 14. Review.

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.

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.

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.

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.

Pérez-Tilve D, González-Matías L, Alvarez-Crespo M, Leiras R, Tovar S, Diéguez C, Mallo F. Exendin-4 potently decreases ghrelin levels in fasting rats. Diabetes. 2007 Jan;56(1):143-51.

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.

Starting date: March 2012
Last updated: July 25, 2013