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

Primary Purpose

Weight Loss, Obesity

Status

Completed

Phase

Phase 3

Locations

United States

Study Type

Interventional

Intervention

Byetta (exenatide)

Weight loss

Metabolic Chamber

Placebo

About this trial

This is an interventional treatment trial for Weight Loss focused on measuring Weight Loss, Byetta (Exenatide), Energy Expenditure, Food Intake, Obesity

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesAccepts Healthy Volunteers

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 over 5 weeks
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), topiramate (with or without phentermine (Qsymia), phentermine (Adipex P) or lorcaserin (Belviq) 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
Personal or family history of multiple endocrine neoplasia (MEN)-2 or medullary thyroid cancer
History of unresolved gallstones
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 <450 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

Sites / Locations

NIDDK, Phoenix

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Exenatide

Placebo

Arm Description

10 micrograms subcutaneously twice

Twice daily

Outcomes

Primary Outcome Measures

Energy Intake

Mean of 3-day food intake change between 3 days (Day 6-7-8) at baseline assessment and 3 days (Day 12-13-14) during the intervention period between the exenatide and placebo groups

Twenty-four-hour Energy Expenditure

Change of twenty-four-hour energy expenditure between at Day 5 at baseline assessment and at Day 11 two days after starting study medication between the exenatide and placebo groups

Secondary Outcome Measures

Body Weight

Mean decrease between pre- and post-randomization in 5 Weeks between the exenatide and placebo groups.

Full Information

NCT ID

NCT00856609

First Posted

March 5, 2009

Last Updated

May 23, 2019

Sponsor

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

1. Study Identification

Unique Protocol Identification Number

NCT00856609

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

January 19, 2018

Overall Recruitment Status

Completed

Study Start Date

March 3, 2009 (undefined)

Primary Completion Date

September 19, 2016 (Actual)

Study Completion Date

September 19, 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Yes

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

Exenatide is an incretin-like drug that has been approved for treatment of type 2 diabetes; it improves glycemia by increasing insulin and decreasing glucagon secretion by pancreatic islet cells and delaying gastric emptying. This randomized, placebo-controlled study is to evaluate whether exenatide over a 5 week period in non-diabetic obese subjects may lead to weight loss. To control for variability in individual response to weight loss treatment, this study will assess the role of exenatide in changing food intake and energy expenditure as possible sources of weight loss. This study will also evaluate the safety profile of exenatide in non-diabetic obese people. Additional assessments will evaluate changes in body fat and hormones involved in the sensations of hunger and fullness.

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 way in which exenatide given twice a day to obese (BMI >= 30 kg/m^2) people without diabetes might lead to weight loss. Because response to weight loss treatment can be highly variable between individuals, we will look at the role of exenatide in changing 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Weight Loss, Obesity

Keywords

Weight Loss, Byetta (Exenatide), Energy Expenditure, Food Intake, Obesity

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

150 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Exenatide

Arm Type

Active Comparator

Arm Description

10 micrograms subcutaneously twice

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Twice daily

Intervention Type

Drug

Intervention Name(s)

Byetta (exenatide)

Intervention Description

Exenatide is an injectable medication

Intervention Type

Behavioral

Intervention Name(s)

Weight loss

Intervention Description

Because response to weight loss

Intervention Type

Other

Intervention Name(s)

Metabolic Chamber

Intervention Description

The subject stays in the small room

Intervention Type

Drug

Intervention Name(s)

Placebo

Primary Outcome Measure Information:

Title

Energy Intake

Description

Mean of 3-day food intake change between 3 days (Day 6-7-8) at baseline assessment and 3 days (Day 12-13-14) during the intervention period between the exenatide and placebo groups

Time Frame

Day 6-7-8 (at baseline) and Day 12-13-14 (3 days after starting study intervention)

Title

Twenty-four-hour Energy Expenditure

Description

Change of twenty-four-hour energy expenditure between at Day 5 at baseline assessment and at Day 11 two days after starting study medication between the exenatide and placebo groups

Time Frame

Day 5 and Day 11

Secondary Outcome Measure Information:

Title

Body Weight

Description

Mean decrease between pre- and post-randomization in 5 Weeks between the exenatide and placebo groups.

Time Frame

5 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

55 Years

Accepts Healthy Volunteers

Eligibility 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 over 5 weeks 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), topiramate (with or without phentermine (Qsymia), phentermine (Adipex P) or lorcaserin (Belviq) 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 Personal or family history of multiple endocrine neoplasia (MEN)-2 or medullary thyroid cancer History of unresolved gallstones 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 <450 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Jonathan Krakoff, M.D.

Organizational Affiliation

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Official's Role

Principal Investigator

Facility Information:

Facility Name

NIDDK, Phoenix

City

Phoenix

State/Province

Arizona

ZIP/Postal Code

85014

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

17379054

Citation

Buse JB, Klonoff DC, Nielsen LL, Guan X, Bowlus CL, Holcombe JH, Maggs DG, Wintle ME. Metabolic effects of two years of exenatide treatment on diabetes, obesity, and hepatic biomarkers in patients with type 2 diabetes: an interim analysis of data from the open-label, uncontrolled extension of three double-blind, placebo-controlled trials. Clin Ther. 2007 Jan;29(1):139-53. doi: 10.1016/j.clinthera.2007.01.015.

Results Reference

background

PubMed Identifier

15504997

Citation

Buse JB, Henry RR, Han J, Kim DD, Fineman MS, Baron AD; Exenatide-113 Clinical Study Group. Effects of exenatide (exendin-4) on glycemic control over 30 weeks in sulfonylurea-treated patients with type 2 diabetes. Diabetes Care. 2004 Nov;27(11):2628-35. doi: 10.2337/diacare.27.11.2628.

Results Reference

background

PubMed Identifier

17622601

Citation

Amori RE, Lau J, Pittas AG. Efficacy and safety of incretin therapy in type 2 diabetes: systematic review and meta-analysis. JAMA. 2007 Jul 11;298(2):194-206. doi: 10.1001/jama.298.2.194.

Results Reference

background

PubMed Identifier

32002540

Citation

Hollstein T, Basolo A, Ando T, Votruba SB, Krakoff J, Piaggi P. Urinary Norepinephrine Is a Metabolic Determinant of 24-Hour Energy Expenditure and Sleeping Metabolic Rate in Adult Humans. J Clin Endocrinol Metab. 2020 Apr 1;105(4):1145-56. doi: 10.1210/clinem/dgaa047.

Results Reference

derived

PubMed Identifier

30651576

Citation

Stinson EJ, Graham AL, Thearle MS, Gluck ME, Krakoff J, Piaggi P. Cognitive dietary restraint, disinhibition, and hunger are associated with 24-h energy expenditure. Int J Obes (Lond). 2019 Jul;43(7):1456-1465. doi: 10.1038/s41366-018-0305-9. Epub 2019 Jan 16.

Results Reference

derived

PubMed Identifier

29596853

Citation

Basolo A, Burkholder J, Osgood K, Graham A, Bundrick S, Frankl J, Piaggi P, Thearle MS, Krakoff J. Exenatide has a pronounced effect on energy intake but not energy expenditure in non-diabetic subjects with obesity: A randomized, double-blind, placebo-controlled trial. Metabolism. 2018 Aug;85:116-125. doi: 10.1016/j.metabol.2018.03.017. Epub 2018 Mar 26.

Results Reference

derived

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

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