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

• Sponsor: Beth Israel Deaconess Medical Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00456885
• Collaborator: Amylin Pharmaceuticals, LLC. (Industry), Eli Lilly and Company (Industry)
• Enrollment: 41
• Location: 1
• Arms: 2
• Duration (Months): 41
• Patients Per Site Per Month: 1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Obesity; Impaired Glucose Tolerance	Drug: exenatide; Drug: Placebo	Phase 4

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 Design

• Study Type: Interventional
• Actual Enrollment: 41 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: The Effect of Exenatide on Body Weight, Energy Expenditure and Hunger in Obese Women Without Diabetes Mellitus
• Study Start Date: Apr 1, 2007
• Actual Primary Completion Date: Sep 1, 2010
• Actual Study Completion Date: Sep 1, 2010

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Change in Weight [16 weeks after the beginning of each treatment]

   Change in weight at the end of each treatment period.

2. Change in Body Mass Index [16 weeks from the start of each treatment period.]

Secondary Outcome Measures

1. Change in Waist Circumference [16 weeks from the start of each treatment period.]

2. Systolic Blood Pressure [16 weeks after the beginning of each treatment]

   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.

3. Changes in Body Composition [16 weeks after the beginning of each treatment]

   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.

4. Changes in Leptin [16 weeks from the start of each treatment period.]

5. Diastolic Blood Pressure [16 weeks after the beginning of each treatment]

6. Adiponectin [16 weeks after the beginning of each treatment]

7. Change in Insulin [16 weeks from the start of each treatment period.]

8. Change in Fasting Glucose [16 weeks from the start of each treatment period.]

9. Change in Two Hour Glucose [16 weeks from the start of each treatment period.]

10. HOMA Score [16 weeks from the start of each treatment period.]

11. REE [16 weeks from the start of each treatment period.]

    Resting Energy Expenditure

Eligibility Criteria

Criteria

• Ages Eligible for Study: 25 Years to 60 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02215

Sponsors and Collaborators

• Beth Israel Deaconess Medical Center
• Amylin Pharmaceuticals, LLC.
• Eli Lilly and Company

Investigators

• Principal Investigator: Eleftheria Maratos-Flier, MD, Beth Israel Deaconess Medical Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Eleftheria Maratos-Flier, Professor of Medicine, Beth Israel Deaconess Medical Center
• ClinicalTrials.gov Identifier: NCT00456885
• Other Study ID Numbers: 2006P000361; BFA912
• First Posted: Apr 5, 2007
• Last Update Posted: Sep 11, 2017
• Last Verified: Aug 1, 2017

• Keywords provided by Eleftheria Maratos-Flier, Professor of Medicine, Beth Israel Deaconess Medical Center: obesity; double blind; placebo controlled; weight loss; appetite; energy expenditure
• Additional relevant MeSH terms: Glucose Intolerance; Exenatide

Study Results

Participant Flow

Recruitment Details	Flyers, Craig's list, posters used for recruitment.Recruitment occurred between 2007 and 2010. After telephone screen subjects were evaluated at the BIDMC clinical research center.

Arm/Group Title	Exenatide First, Then Placebo	Placebo First, Then Exenatide
Arm/Group Description	Started on exenatide, 3 week washout, started on placebo.	Started on placebo, three week washout, started on exenatide.
Period Title: First Treatment Period, 16 Weeks
STARTED	24	17
COMPLETED	24	17
NOT COMPLETED	0	0
Period Title: First Treatment Period, 16 Weeks
STARTED	24	17
COMPLETED	24	17
NOT COMPLETED	0	0
Period Title: First Treatment Period, 16 Weeks
STARTED	24	17
COMPLETED	23	17
NOT COMPLETED	1	0

Baseline Characteristics

Arm/Group Title	All Study Participants
Arm/Group Description	All participants in the study.
Overall Participants	41
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	48 (11)
Sex: Female, Male (Count of Participants)
Female	41 100%
Male	0 0%
Region of Enrollment (participants) [Number]
United States	41 100%
Weight (Kilograms) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Kilograms]	89 (14)
BMI (Kg/meter^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Kg/meter^2]	33 (4)
HOMA IR (Ratio) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Ratio]	2 (1)
Waist (centrimeters) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [centrimeters]	105 (12)
Body Fat (percent) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [percent]	40 (5)
Systolic BP (mm of mercury) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mm of mercury]	128 (14)
Diastolic BP (mm of Mercury) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mm of Mercury]	75 (8)
HDL (mg/dl) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dl]	62 (19)
LDL (mg/dl) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dl]	114 (28)
Total Cholesterol (mg/dl) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dl]	198 (32)
Triglycerides (mg/dl) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dl]	111 (64)
Fasting Insulin (mU per liter) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mU per liter]	8 (6)
Fasting Glucose (mg/dl) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dl]	85 (12)
Two Hour Glucose (mg/dl) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dl]	110 (32)
Adiponectin (micrograms/ml) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [micrograms/ml]	6 (3)
Leptin (ng/ml) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [ng/ml]	36 (18)
Resting Energy Expenditure (Kilocalories) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Kilocalories]	1439 (196)

Outcome Measures

1. Primary Outcome

Title	Change in Weight
Description	Change in weight at the end of each treatment period.
Time Frame	16 weeks after the beginning of each treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Exenatide	Placebo
Arm/Group Description	All participants that received exenatide.	All participants that received placebo.
Measure Participants	41	40
Mean (Standard Error) [kilograms]	-2.49 (0.66)	0.43 (0.63)

2. Primary Outcome

Title	Change in Body Mass Index
Time Frame	16 weeks from the start of each treatment period.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Exenatide	Placebo
Arm/Group Description	All participants that received exenatide.	All participants that received placebo.
Measure Participants	41	40
Mean (95% Confidence Interval) [Kg/m^2]	-0.93	0.18

3. Secondary Outcome

Title	Change in Waist Circumference
Time Frame	16 weeks from the start of each treatment period.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Exenatide	Placebo
Arm/Group Description	All participants that received exenatide.	All participants that received placebo.
Measure Participants	41	40
Mean (95% Confidence Interval) [centimeters]	-1.68	0.94

4. Secondary Outcome

Title	Systolic Blood Pressure
Description	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.
Time Frame	16 weeks after the beginning of each treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Exenatide	Placebo
Arm/Group Description	All participants that received exenatide.	All participants that received placebo.
Measure Participants	41	40
Mean (95% Confidence Interval) [mm of mercury]	-2.5	-1.3

5. Secondary Outcome

Title	Changes in Body Composition
Description	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.
Time Frame	16 weeks after the beginning of each treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Exenatide	Placebo
Arm/Group Description	All participants that received exenatide.	All participants that received placebo.
Measure Participants	41	40
Mean (95% Confidence Interval) [per cent]	-0.4	-0.7

6. Secondary Outcome

Title	Changes in Leptin
Time Frame	16 weeks from the start of each treatment period.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Exenatide	Placebo
Arm/Group Description	All participants that received exenatide.	All participants that received placebo.
Measure Participants	41	40
Mean (95% Confidence Interval) [ng/ml]	-3.7	-0.2

7. Secondary Outcome

Title	Diastolic Blood Pressure
Time Frame	16 weeks after the beginning of each treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Exenatide	Placebo
Arm/Group Description	All participants that received exenatide.	All participants that received placebo.
Measure Participants	41	40
Mean (95% Confidence Interval) [mm of mercury]	-1.2	-0.4

8. Secondary Outcome

Title	Adiponectin
Time Frame	16 weeks after the beginning of each treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Exenatide	Placebo
Arm/Group Description	All participants that received exenatide.	All participants that received placebo.
Measure Participants	41	40
Mean (95% Confidence Interval) [microgram per ml]	0.4	0.07

9. Secondary Outcome

Title	Change in Insulin
Time Frame	16 weeks from the start of each treatment period.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Exenatide	Placebo
Arm/Group Description	All participants that received exenatide.	All participants that received placebo.
Measure Participants	41	40
Mean (95% Confidence Interval) [microunits per liter]	1.1	0.4

10. Secondary Outcome

Title	Change in Fasting Glucose
Time Frame	16 weeks from the start of each treatment period.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Exenatide	Placebo
Arm/Group Description	All participants that received exenatide.	All participants that received placebo.
Measure Participants	41	40
Mean (95% Confidence Interval) [mg/dl]	0.5	3.1

11. Secondary Outcome

Title	Change in Two Hour Glucose
Time Frame	16 weeks from the start of each treatment period.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Exenatide	Placebo
Arm/Group Description	All participants that received exenatide.	All participants that received placebo.
Measure Participants	41	40
Mean (95% Confidence Interval) [mg/dl]	-10	-0.5

12. Secondary Outcome

Title	HOMA Score
Time Frame	16 weeks from the start of each treatment period.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Exenatide	Placebo
Arm/Group Description	All participants that received exenatide.	All participants that received placebo.
Measure Participants	41	40
Mean (95% Confidence Interval) [Ratio fasting glucose to insulin]	0.2	0.2

13. Secondary Outcome

Title	REE
Description	Resting Energy Expenditure
Time Frame	16 weeks from the start of each treatment period.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Exenatide	Placebo
Arm/Group Description	All participants that received exenatide.	All participants that received placebo.
Measure Participants	41	40
Mean (95% Confidence Interval) [Kilocalories]	-13.7	6.5

Adverse Events

Time Frame	37 weeks
Adverse Event Reporting Description	Adverse effects were monitored as all participant adverse events and were not monitored by intervention or sequence.
Arm/Group Title	All Study Participants
Arm/Group Description
All Cause Mortality
	All Study Participants
	Affected / at Risk (%)	# Events
Total	0/41 (0%)
Serious Adverse Events
	All Study Participants
	Affected / at Risk (%)	# Events
Total	0/41 (0%)
Other (Not Including Serious) Adverse Events
	All Study Participants
	Affected / at Risk (%)	# Events
Total	31/41 (75.6%)
Gastrointestinal disorders
Nausea	31/41 (75.6%)
Bloating	1/41 (2.4%)	1
Constipation	2/41 (4.9%)	2
Heartburn	1/41 (2.4%)	1
Diarrhea	1/41 (2.4%)	1
General disorders
Fatigue	1/41 (2.4%)	1
Skin and subcutaneous tissue disorders
Irritation at injection site	1/41 (2.4%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.