The Effects of Exenatide (Byetta ) on Energy Expenditure and Weight Loss in Nondiabetic Obese Subjects

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by National Institutes of Health Clinical Center (CC)
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) )
ClinicalTrials.gov Identifier:
NCT00856609
First received: March 5, 2009
Last updated: April 3, 2014
Last verified: March 2014

March 5, 2009
April 3, 2014
March 2009
June 2016   (final data collection date for primary outcome measure)
Exenatide effects on weight loss, energy expenditure & amp; food intake [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
Exenatide effects on wt loss, enerfy expenditure & food intake
Complete list of historical versions of study NCT00856609 on ClinicalTrials.gov Archive Site
Weight loss maintenance, decreased fat mass, decreased food intake and increased energy expenditure with extended exenatide treatment [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
Weight loss maintenance, decreased fat mass, decreased food intake and increased energy expenditure with extended exenatide treatment
Not Provided
Not Provided
 
The Effects of Exenatide (Byetta ) on Energy Expenditure and Weight Loss in Nondiabetic Obese Subjects
The Effects of Exenatide (Byetta) on Energy Expenditure and Weight Loss in Non-Diabetic Obese Subjects

Background:

  • Obesity can lead to a number of health problems, including diabetes, heart disease, stroke, low back pain, fatty liver disease, and osteoarthritis. The medical treatments currently available for obesity are limited.
  • Exenatide is an injectable medication approved for treatment of Type 2 diabetes that causes weight loss in some diabetic subjects. If exenatide works for weight loss in nondiabetic persons is not known.

Objectives:

  • To determine whether nondiabetic obese individuals treated with exenatide as compared with those treated with placebo will lose a greater amount of weight and have body composition changes over a 24-week period, and whether the loss and body composition changes will be maintained during a 24-week extension period.
  • To determine whether exenatide leads to a decrease in food intake.
  • To determine whether change in caloric intake correlates with exenatide-induced changes in stomach emptying time.
  • To determine the effects of exenatide on energy expenditure.
  • To determine the effects of exenatide on carbohydrate versus fat use by the body for energy needs.
  • To determine the effects of exenatide on activity levels.
  • To determine whether exenatide alters hormonal levels, and the association of any changes with energy intake and expenditure, future weight loss, and percent body fat changes.
  • To determine whether exenatide alters responses to behavioral testing via questionnaires specifically addressing dietary restraint and stress-related eating behaviors and the relationship of any changes to food intake, hormone levels, weight loss, and fat loss.
  • To assess the tolerability and safety profile of exenatide in nondiabetic obese subjects.

Eligibility:

  • Nondiabetic men and (premenopausal) women between the ages of 18 and 55 years who have a body mass index greater than 30 kg/m(2) and live in the Phoenix, AZ area.

Design:

  • Participants will be admitted for an initial 16-day period to the research unit, during which the following will occur:
  • Instructions on lifestyle changes to promote weight loss
  • Questionnaires to determine eating-related behaviors and attitudes toward food
  • Laboratory testing to determine glucose tolerance, body composition, stomach emptying time, hormone levels, energy expenditure and food intake both before and after starting the study medication
  • Instructions on self-injecting exenatide or placebo via a medication pen
  • Instructions on the use of blood glucose monitors and logs
  • Following release, participants will self-administer a set dose of either exenatide or a placebo 2 times per day for 24 weeks. Participants will not know whether they are receiving exenatide or placebo.
  • Outpatient visits occur weekly for the first 4 weeks and then once every 4 weeks, during which weight loss, compliance with self-medication, side effects, and lifestyle modifications will be assessed.
  • Participants will be readmitted to the metabolic unit during the 24th week of the study, during which the studies from the initial stay will be repeated.
  • Participants wishing to continue into the 24-week open-label extension period will be seen as outpatients as described in the initial part of the study.

Obesity can lead to a number of health problems including diabetes, heart disease, stroke, low back pain, fatty liver disease, and osteoarthritis. The medical treatments currently available for obesity are limited. Exenatide is an injectable medication approved for treatment of type 2 diabetes that causes weight loss in some diabetic subjects. The reasons exenatide is thought to cause weight loss include decreased food intake, increased feelings of fullness and nausea. Because levels of a human gut hormone (glucagon like peptide 1) that is similar to exenatide have been shown to be related to resting energy expenditure, it is also possible that exenatide may have effects on a person s metabolism, a.k.a. energy expenditure, but any effect of exenatide on energy expenditure has yet to be evaluated. Even though exenatide is used to treat diabetes, administration of exenatide to non-diabetic lean individuals did not cause frankly low blood sugars.

The primary goal of this study is to investigate the use of exenatide given twice a day as a weight loss medication in obese (BMI greater than or equal to 30 kg/m(2)) people without diabetes. Because response to weight loss treatment can be highly variable between individuals, our other goals will be to look at the role of exenatide related changes in food intake and energy expenditure as possible explanations for weight loss. We will also assess the safety profile of exenatide in non-diabetic obese people.

This study will involve the use of exenatide or placebo, determined randomly, in obese individuals without diabetes over a 5-week period. The primary measurements will include effects of exenatide on energy expenditure and food intake. We will also look at changes in body fat and the levels of hormones involved in the sensations of hunger and fullness. We will assess if any exenatide-induced changes can predict which individuals lose weight over the 5 weeks. The safety and side effects of exenatide in non-diabetic individuals during this time will also be determined. Findings from this study would help to determine how exenatide works to cause weight loss in people without diabetes, who might benefit most, and would help to improve understanding of why some people respond better to weight loss treatment than others.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
  • Weight Loss
  • Obesity
  • Drug: Byetta (exenatide)
    N/A
  • Behavioral: Weight loss
    N/A
  • Procedure: Metabolic Chamber
    N/A
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
Not Provided
June 2016
June 2016   (final data collection date for primary outcome measure)
  • INCLUSION CRITERIA:
  • Premenopausal women and men < 55 years of age
  • BMI > 30 kg/m(2)
  • Expressed desire for weight loss
  • Stable weight (variation < 2.3 kg within past 6 months)
  • Ability to provide informed consent
  • Ability to follow verbal and written instructions
  • Nonsmoker
  • Ability to commute to study site on a regular basis for short outpatient visits
  • For females, use of a medically approved form of contraception. For oral contraceptives, subjects will need to be on an established dose for at least 3 months to ensure stable weight and will be asked not to switch contraceptive methods during study participation.

EXCLUSION CRITERIA:

  • Age < 18 years
  • Use of other medications to treat obesity including medications obtained over the counter or internet, orlistat (Xenical, Alli), sibutramine (Meridia), or phentermine (Adipex P) within the past 6 months
  • History of an eating disorder including anorexia or bulimia
  • History of surgery for the treatment of obesity (gastric banding, gastric bypass)
  • Diagnosis of type 1 or type 2 diabetes mellitus according to American Diabetes Association guidelines
  • Previous exposure to exenatide
  • Uncontrolled hypertension as defined by a blood pressure of 150/90 on two or more occasions or use of antihypertensive medications which may affect energy expenditure including alpha blockers, beta blockers, angiotensin receptor blockers or inhibitors of angiotensin converting enzyme
  • Current use of tobacco products, marijuana, amphetamines, cocaine or intravenous drug use
  • Chronic ethanol use (> 3 drinks /day)
  • Endocrine disorders including hypo or hyperthyroidism (including subclinical disease), Cushing s disease, growth hormone deficiency or other pituitary diseases
  • History of pancreatitis
  • Hyperamylasemia
  • Fasting triglyceride level greater than or equal to 500
  • Gastroparesis
  • Inflammatory bowel disease or malabsorption disorders
  • Malignancy treated with chemotherapy or radiation within the past 5 years
  • Current clinical depression, diagnosis of psychosis or recent use of psychotropic medication
  • Pregnancy within past 6 months
  • Breastfeeding
  • Failure to use medically approved contraceptive methods if subject is female
  • Liver function abnormalities (transaminases greater than twice normal)
  • Renal insufficiency (creatinine clearance < 50 ml/min)
  • History of chronic infection including tuberculosis, coccidiomycoses, lyme disease or HIV infection
  • Pulmonary disorders, including chronic obstructive pulmonary disease, which would limit ability to follow the protocol (investigator judgment)
  • Cardiovascular disease including history of myocardial infarction, unstable angina or heart failure
  • Central nervous system disease, including history of cerebrovascular accidents, dementia, and neurodegenerative disorders
  • Weight > 350 pounds (maximum weight of the DXA machine as per manufacturer s manual)
  • Sensitivity to exenatide or any inert components in its formulation
  • Sensitivity to acetaminophen
  • Conditions not specifically mentioned above may serve as criteria for exclusion at the discretion of the investigators
Both
18 Years to 55 Years
Yes
Contact: Marie S. Thearle, M.D. (602) 200-5304 thearlem@mail.nih.gov
United States
 
NCT00856609
999909095, 09-DK-N095
Not Provided
National Institutes of Health Clinical Center (CC) ( National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) )
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Not Provided
Principal Investigator: Marie S. Thearle, M.D. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
National Institutes of Health Clinical Center (CC)
March 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP