The Effect of Exenatide on Weight and Hunger in Obese, Healthy Women

Study Overview
=================
Brief Summary
-----------------
This study will look at the effect of exenatide, a drug which has been approved for the treatment of type 2 diabetes, on body weight, appetite and energy expenditure among moderately obese women without diabetes. The study is 35 weeks long and includes 19 outpatient visits. Participants will receive exenatide for 16 weeks and placebo for 16 weeks with a 3 week rest period in between. Neither participants nor investigators will know whether exenatide or placebo is being administered. Participants will be started randomly on either exenatide or placebo. Our hypothesis is that treatment with exenatide will curb appetite and lead to weight loss and may lead to changes in energy expenditure.

Detailed Description
-----------------
This study will examine the effect of exenatide on body weight, energy expenditure, satiety, sleep, and metabolic parameters in healthy, moderately obese women (BMI 28-35 kg/m2). We will look at 2 populations of women, one with normal glucose metabolism and one with impaired glucose homeostasis (IGH)--either impaired fasting glucose (IFG, fasting glucose 101-125 mg/dL) or impaired glucose tolerance (IGT, glucose 140-199 mg/dL 2h after a 75g oral glucose load). This is a randomized, double blind, crossover study with two 16-week treatment periods separated by a 3-week washout period. There are 19 study visits over 35 weeks. The goals of this study are 1) to examine the effect of exenatide on body weight and dysglycemia in populations in which this medication has not been studied, namely obese women with and without IGH and 2) to investigate possible mechanisms of weight loss through measurements of energy expenditure, hunger, satiety, nausea, and sleep. The primary outcome of this study is weight loss. We will calculate absolute and relative change in body weight from baseline to week 16 (the first treatment period) and from week 19 to week 35 (the second treatment period). Body weight will be measured at every study visit which will also allow us to assess the absolute and relative change from baseline throughout the entire study.

Official Title
-----------------
The Effect of Exenatide on Body Weight, Energy Expenditure and Hunger in Obese Women Without Diabetes Mellitus

Conditions
-----------------
Obesity, Impaired Glucose Tolerance

Intervention / Treatment
-----------------
* Drug: exenatide
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Females aged 25-60 BMI 28-35 kg/m2 No known diagnosis of diabetes No known diagnosis of coronary heart disease Self-described sedentary lifestyle with minimal regular cardiovascular exercise (no more than 1 hour per week) Stable weight (variation < 3 kg within 6 months of screening visit) Ability to give informed consent Ability to follow verbal and written instructions Use of medically approved form of contraception (monophasic oral contraception, intra uterine device, surgical sterilization or 2 combined barrier methods) Nonsmoker (tobacco, marijuana) Outpatient visits every 2 weeks throughout the study period are required. While most of these visits are short (15 minutes)ability to commute to the performance site in Boston, on a regular basis, is necessary. Exclusion Criteria: Type 1 or type 2 diabetes mellitus diagnosed according to American Diabetes Association criteria Coronary heart disease (history of myocardial infarction or unstable angina pectoris) Uncontrolled hypertension hypertension (BP > 150/90 mmHg on or off antihypertensive medication) Uncontrolled dyslipidemia (LDL > 200 or TG > 400 on or off lipid lowering medication) Tobacco, marijuana or intravenous drug use Shift workers (night shift or alternating day/night shifts) Recent weight loss (> 3 kg within 4 months of the screening visit) Gastroparesis Inflammatory bowel disease Malignancy treated with chemotherapy within the past 3 years History of pancreatitis Depression requiring hospitalization or diagnosis of psychosis Renal insufficiency (creatinine clearance < 50 ml/min) Transaminases > 2x above the normal range Pregnancy within 6 months of the screening visit Breastfeeding Failure to use medically approved contraceptive methods History of an eating disorder (anorexia, bulimia or laxative abuse) History of surgery for the treatment of obesity (gastric banding, gastric bypass, gastric stapling) New diagnosis of hypo or hyperthyroidism within 1 year of screening visit Previous participation in a clinical study with exenatide Presence or history of allergic reaction to multiple drugs

Ages Eligible for Study
-----------------
Minimum Age: 25 Years
Maximum Age: 60 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Exenatide First<br>Started on Exenatide, 3 week washout, start placebo | Drug: exenatide<br>* 5 microgram twice a day for two week and then 10 mcg for remaining 15 weeks<br>* Other names: Byetta;Drug: Placebo<br>* Twice daily injection of placebo<br>|
| Experimental: Placebo First<br>Started on placebo, 3 week washout, start exenatide | Drug: exenatide<br>* 5 microgram twice a day for two week and then 10 mcg for remaining 15 weeks<br>* Other names: Byetta;Drug: Placebo<br>* Twice daily injection of placebo<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Weight | Change in weight at the end of each treatment period. | 16 weeks after the beginning of each treatment | 
| Change in Body Mass Index |  | 16 weeks from the start of each treatment period. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Waist Circumference |  | 16 weeks from the start of each treatment period. | 
| Systolic Blood Pressure | Blood pressure was measured using a Dynamap automated monitoring device. The change is reported as the blood pressure measured at the beginning of the treatment group and after 16 weeks. We are reporting the change in the systolic blood presssure recorded. | 16 weeks after the beginning of each treatment | 
| Changes in Body Composition | Per cent body body fat was assessed using bio-electrical impedance with a BIA; RJL System Quantum II Bioelectrical Body Composition Analyzer. The data is reported as per cent body fat. | 16 weeks after the beginning of each treatment | 
| Changes in Leptin |  | 16 weeks from the start of each treatment period. | 
| Diastolic Blood Pressure |  | 16 weeks after the beginning of each treatment | 
| Adiponectin |  | 16 weeks after the beginning of each treatment | 
| Change in Insulin |  | 16 weeks from the start of each treatment period. | 
| Change in Fasting Glucose |  | 16 weeks from the start of each treatment period. | 
| Change in Two Hour Glucose |  | 16 weeks from the start of each treatment period. | 
| HOMA Score |  | 16 weeks from the start of each treatment period. | 
| REE | Resting Energy Expenditure | 16 weeks from the start of each treatment period. | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
obesity, double blind, placebo controlled, weight loss, appetite, energy expenditure