Clinical trial NCT00456885: The Effect of Exenatide on Weight and Hunger in Obese, Healthy Women
Official title: The Effect of Exenatide on Body Weight, Energy Expenditure and Hunger in Obese Women Without Diabetes Mellitus
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Obesity
Impaired Glucose Tolerance
Keywords: obesity
double blind
placebo controlled
weight loss
appetite
energy expenditure
Lead sponsor: Beth Israel Deaconess Medical Center
Sponsor class: OTHER
Collaborators: name: Amylin Pharmaceuticals, LLC.
name: Eli Lilly and Company
First posted: 2007-04-05
Enrollment: 41
Sex: FEMALE
Minimum age (years): 25
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

1. Females aged 25-60
2. BMI 28-35 kg/m2
3. No known diagnosis of diabetes
4. No known diagnosis of coronary heart disease
5. Self-described sedentary lifestyle with minimal regular cardiovascular exercise (no more than 1 hour per week)
6. Stable weight (variation \< 3 kg within 6 months of screening visit)
7. Ability to give informed consent
8. Ability to follow verbal and written instructions
9. Use of medically approved form of contraception (monophasic oral contraception, intra uterine device, surgical sterilization or 2 combined barrier methods)
10. Nonsmoker (tobacco, marijuana)
11. 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:

1. Type 1 or type 2 diabetes mellitus diagnosed according to American Diabetes Association criteria
2. Coronary heart disease (history of myocardial infarction or unstable angina pectoris)
3. Uncontrolled hypertension hypertension (BP \> 150/90 mmHg on or off antihypertensive medication)
4. Uncontrolled dyslipidemia (LDL \> 200 or TG \> 400 on or off lipid lowering medication)
5. Tobacco, marijuana or intravenous drug use
6. Shift workers (night shift or alternating day/night shifts)
7. Recent weight loss (\> 3 kg within 4 months of the screening visit)
8. Gastroparesis
9. Inflammatory bowel disease
10. Malignancy treated with chemotherapy within the past 3 years
11. History of pancreatitis
12. Depression requiring hospitalization or diagnosis of psychosis
13. Renal insufficiency (creatinine clearance \< 50 ml/min)
14. Transaminases \> 2x above the normal range
15. Pregnancy within 6 months of the screening visit
16. Breastfeeding
17. Failure to use medically approved contraceptive methods
18. History of an eating disorder (anorexia, bulimia or laxative abuse)
19. History of surgery for the treatment of obesity (gastric banding, gastric bypass, gastric stapling)
20. New diagnosis of hypo or hyperthyroidism within 1 year of screening visit
21. Previous participation in a clinical study with exenatide
22. Presence or history of allergic reaction to multiple drugs

Primary outcomes:
measure: Change in Weight
timeFrame: 16 weeks after the beginning of each treatment
measure: Change in Body Mass Index
timeFrame: 16 weeks from the start of each treatment period.
Secondary outcomes:
measure: Change in Waist Circumference
timeFrame: 16 weeks from the start of each treatment period.
measure: Systolic Blood Pressure
timeFrame: 16 weeks after the beginning of each treatment
measure: Changes in Body Composition
timeFrame: 16 weeks after the beginning of each treatment
measure: Changes in Leptin
timeFrame: 16 weeks from the start of each treatment period.
measure: Diastolic Blood Pressure
timeFrame: 16 weeks after the beginning of each treatment
measure: Adiponectin
timeFrame: 16 weeks after the beginning of each treatment
measure: Change in Insulin
timeFrame: 16 weeks from the start of each treatment period.
measure: Change in Fasting Glucose
timeFrame: 16 weeks from the start of each treatment period.
measure: Change in Two Hour Glucose
timeFrame: 16 weeks from the start of each treatment period.
measure: HOMA Score
timeFrame: 16 weeks from the start of each treatment period.
measure: REE
timeFrame: 16 weeks from the start of each treatment period.
Other outcomes:
Locations:
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
Study officials:
affiliation: Beth Israel Deaconess Medical Center
name: Eleftheria Maratos-Flier, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Dushay J, Gao C, Gopalakrishnan GS, Crawley M, Mitten EK, Wilker E, Mullington J, Maratos-Flier E. Short-term exenatide treatment leads to significant weight loss in a subset of obese women without diabetes. Diabetes Care. 2012 Jan;35(1):4-11. doi: 10.2337/dc11-0931. Epub 2011 Oct 31.