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

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

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.

Study Overview

• Status: Completed
• Conditions: Obesity; Impaired Glucose Tolerance
• Intervention / Treatment: Drug: exenatide; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 41
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years to 60 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

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

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.

Collaborators and Investigators

• Sponsor: Beth Israel Deaconess Medical Center
• Collaborators: Eli Lilly and Company; Amylin Pharmaceuticals, LLC.

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: April 1, 2007
• Primary Completion (Actual): September 1, 2010
• Study Completion (Actual): September 1, 2010

Study Registration Dates

• First Submitted: April 4, 2007
• First Submitted That Met QC Criteria: April 4, 2007
• First Posted (Estimate): April 5, 2007

Study Record Updates

• Last Update Posted (Actual): September 11, 2017
• Last Update Submitted That Met QC Criteria: August 9, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Keywords: obesity; appetite; weight loss; placebo controlled; energy expenditure; double blind
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Hyperglycemia; Glucose Intolerance; Hypoglycemic Agents; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Anti-Obesity Agents; Incretins; Exenatide
• Other Study ID Numbers: 2006P000361; BFA912