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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
  Purpose

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.

Condition Intervention Phase
Weight Loss
Obesity
Drug: Byetta (exenatide)
Behavioral: Weight loss
Procedure: Metabolic Chamber
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: The Effects of Exenatide (Byetta) on Energy Expenditure and Weight Loss in Non-Diabetic Obese Subjects

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Exenatide effects on weight loss, energy expenditure & amp; food intake [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ]

Study Start Date: March 2009
Estimated Study Completion Date: June 2016
Estimated Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Byetta (exenatide)
    N/A
    Behavioral: Weight loss
    N/A
    Procedure: Metabolic Chamber
    N/A
Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00856609

Contacts
Contact: Marie S. Thearle, M.D. (602) 200-5304 thearlem@mail.nih.gov

Locations
United States, Arizona
NIDDK, Phoenix Recruiting
Phoenix, Arizona, United States, 85014
Contact: Marie Thearle, M.D.    602-200-5304    thearlem@mail.nih.gov   
Sponsors and Collaborators
Investigators
Principal Investigator: Marie S. Thearle, M.D. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
  More Information

Publications:
Responsible Party: National Institutes of Health Clinical Center (CC) ( National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) )
ClinicalTrials.gov Identifier: NCT00856609     History of Changes
Other Study ID Numbers: 999909095, 09-DK-N095
Study First Received: March 5, 2009
Last Updated: April 3, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Weight Loss
Byetta (Exenatide)
Energy Expenditure
Obesity
Food Intake

Additional relevant MeSH terms:
Nutrition Disorders
Body Weight
Obesity
Weight Loss
Body Weight Changes
Overnutrition
Overweight
Signs and Symptoms
Exenatide
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Hypoglycemic Agents
Incretins
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on November 27, 2014