Weight Loss With Exenatide Treatment

• Sponsor: Jody Dushay (Other)
• Overall Status: Completed
• CT.gov ID: NCT01590433
• Collaborator: AstraZeneca (Industry)
• Enrollment: 249
• Location: 1
• Arms: 2
• Duration (Months): 82
• Patients Per Site Per Month: 3

Study Details

Study Description

Brief Summary

The investigators are conducting a study that will investigate the possible mechanisms of weight loss associated with exenatide treatment and the metabolic characteristics of high responders (i.e. subjects who achieve greater than 5% weight loss) to exenatide treatment. The investigators will also examine the magnitude and duration of weight loss among a cohort of high responders over 52 weeks of treatment, and at 3 and 6 months following treatment.

Hypothesis:

The mechanisms of weight loss with exenatide are not fully understood, and weight loss responses to exenatide are highly variable, possibly reflecting distinct metabolic parameters. By identifying and following a group of obese women who lose greater than 5% body weight after short-term exenatide treatment, the investigators can gain insights into the possible mechanisms of weight loss and assess long-term weight loss with this pharmacotherapeutic intervention.

Condition or Disease	Intervention/Treatment	Phase
Obesity	Drug: Exenatide; Drug: Placebo; Behavioral: Dietary counseling	Phase 4

Detailed Description

Primary Outcomes

The primary objectives of this study is:

• To investigate possible mechanisms and patterns of weight loss with exenatide treatment, especially among individuals who have robust early weight loss (greater than 5% weight loss in 12 weeks) with exenatide.

Secondary Outcomes

Our secondary objective is to identify metabolic characteristics that predict robust response to exenatide treatment.

Outcome measurements:

• Weight

• Body composition

• Resting energy expenditure (REE)

• Mixed meal test

• Thermic effect of food

• Serum metabolic parameters

• Hunger/Nausea/Satiety visual analog scales (VAS)

• Physical activity monitoring

Study Population

The study population will be generally healthy, non-diabetic women age 18-70 years with BMI 28-48 kg/m^2.

Study Design

• Study Type: Interventional
• Actual Enrollment: 249 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Participant)
• Primary Purpose: Treatment
• Official Title: A Prospective Study of Patterns, Predictors, and Mechanisms of Weight Loss With Exenatide Treatment in Overweight and Obese Women Without Diabetes
• Study Start Date: Mar 1, 2012
• Actual Primary Completion Date: Jan 1, 2019
• Actual Study Completion Date: Jan 1, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Exenatide Subjects will be randomly assigned to the exenatide study treatment group or to the placebo study treatment group. Subjects will have a 33 percent chance of being assigned to the placebo study treatment group and a 66 percent chance of being assigned to exenatide study treatment. Subjects will not be able to choose the study group to which they will be assigned. All study participants will receive individualized dietary counseling based on food logs. Subjects who receive exenatide will not be assigned to follow a reduced-calorie diet in addition to study treatment. Subjects will not know whether they are receiving exenatide or placebo, but the unblinded members of study team will know which they are receiving.	Drug: Exenatide; Subjects will inject 5mcg of exenatide subcutaneously 15 minutes before the morning and evening meal for the first 2 weeks of the study. At study week 2, subjects will increase to 10mcg twice daily for the remainder of the study.
Placebo Comparator: Placebo Subjects will be randomly assigned to the exenatide study treatment group or to the placebo study treatment group. Subjects will have a 33 percent chance of being assigned to the placebo study treatment group and a 66 percent chance of being assigned to exenatide study treatment. Subjects will not be able to choose the study group to which they will be assigned. All study participants will receive individualized dietary counseling based on food logs. Subjects who receive placebo will be assigned to follow a reduced-calorie diet in addition to study treatment. Subjects will not know whether they are receiving exenatide or placebo, but the unblinded members of the study team will know which they are receiving.	Drug: Placebo; Subjects will inject 5mcg of identically dispensed placebo subcutaneously 15 minutes before the morning and evening meal for the first 2 weeks of the study. At study week 2, subjects will increase to 10mcg twice daily for the remainder of the study.; Behavioral: Dietary counseling; All subjects will also receive individualized dietary counseling. Subjects in the placebo group will be counseled to follow a hypocaloric diet.

Outcome Measures

Primary Outcome Measures

1. Change in Body Weight [12 weeks]

   Change in body weight after 12 weeks of treatment with exenatide or placebo twice daily injections. This outcome compares baseline and 12 week body weight.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Females age 18-70

• BMI 28-48 kg/m^2

• Stable weight (greater than 3 kg weight gain or loss within 6 months of screening visit).

• Ability to give informed consent and follow verbal and written instructions in English.

Exclusion Criteria:

• Type 1 or type 2 diabetes mellitus diagnosed according to American Diabetes Association criteria

• Unstable heart disease as evidenced by ongoing angina

• Congestive heart failure

• Uncontrolled hypertension (BP greater than 170/100 mmHg on or off antihypertensive medication)

• Uncontrolled dyslipidemia (LDL greater than 200 or TG greater than 400 on or off lipid lowering medication)

• Tobacco, marijuana, cocaine, or intravenous drug use

• Shift workers (night shift or alternating day/night shifts)

• Gastroparesis

• Inflammatory bowel disease or irritable bowel syndrome

• Malignancy treated with chemotherapy within the past 3 years

• History of pancreatitis

• Depression requiring hospitalization or diagnosis of psychosis

• Renal insufficiency (eGFR less than 50)

• Transaminases greater than 2 times above the normal range

• Pregnancy within 6 months of the screening visit

• Lactation

• Failure to use medically approved contraceptive methods (monophasic oral contraception, intra uterine device, surgical sterilization or 2 combined barrier methods)

• History of an eating disorder (anorexia, bulimia or laxative abuse)

• Treatment with FDA-approved or over-the-counter weight loss medication within 6 months, with the exception of Xenical if there was no weight loss

• History of gastric bypass surgery or gastric stapling

• Biochemical evidence of hyper or hypothyroidism, or new diagnosis of hypo or hyperthyroidism within 3 months of screening visit

• Previous treatment with exenatide

• Discretion of the PI

Contacts and Locations

Locations

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

Sponsors and Collaborators

• Jody Dushay
• AstraZeneca

Investigators

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

Study Documents (Full-Text)

• Study Protocol, Statistical Analysis Plan, and Informed Consent Form - Jan 9, 2018

More Information

Publications

None provided.

• Responsible Party: Jody Dushay, Assistant Professor of Medicine, Beth Israel Deaconess Medical Center
• ClinicalTrials.gov Identifier: NCT01590433
• Other Study ID Numbers: 2011P000310
• First Posted: May 3, 2012
• Last Update Posted: Jun 23, 2021
• Last Verified: Jun 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Jody Dushay, Assistant Professor of Medicine, Beth Israel Deaconess Medical Center: Obesity; Overweight; Exenatide; Diet; Women
• Additional relevant MeSH terms: Weight Loss; Exenatide

Study Results

Participant Flow

Pre-assignment Detail	249 subjects provided informed consent, 182 were randomized. I am reporting that 249 subjects were enrolled according to our local IRB definition of enrollment. 182 started study treatment. 67 subjects who did not start treatment were either found to be ineligible based on screening labs; withdrew consent; or were lost to followup.

Arm/Group Title	Exenatide	Placebo
Arm/Group Description	Subjects will be randomly assigned to the exenatide study treatment group or to the placebo study treatment group. Subjects will inject 5mcg of exenatide or identically dispensed placebo subcutaneously 15 minutes before the morning and evening meal for the first 2 weeks of the study. At study week 2, subjects will increase to 10mcg twice daily for the remainder of the study.	Subjects will be randomly assigned to the exenatide study treatment group or to the placebo study treatment group. Subjects will inject 5mcg of exenatide or identically dispensed placebo subcutaneously 15 minutes before the morning and evening meal for the first 2 weeks of the study. At study week 2, subjects will increase to 10mcg twice daily for the remainder of the study.
Period Title: Overall Study
STARTED	127	55
COMPLETED	75	33
NOT COMPLETED	52	22

Baseline Characteristics

Arm/Group Title	Exenatide	Placebo	Total
Arm/Group Description	Subjects will be randomly assigned to the exenatide study treatment group or to the placebo study treatment group. Exenatide: Subjects will inject 5mcg of exenatide or identically dispensed placebo subcutaneously 15 minutes before the morning and evening meal for the first 2 weeks of the study. At study week 2, subjects will increase to 10mcg twice daily for the remainder of the study.	Subjects will be randomly assigned to the exenatide study treatment group or to the placebo study treatment group. Placebo: Subjects will inject 5mcg of exenatide or identically dispensed placebo subcutaneously 15 minutes before the morning and evening meal for the first 2 weeks of the study. At study week 2, subjects will increase to 10mcg twice daily for the remainder of the study. Dietary counseling: All subjects will also receive individualized dietary counseling. Subjects may or may not be asked to follow a reduced calorie diet in addition to receiving treatment.	Total of all reporting groups
Overall Participants	127	55	182
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	43.9 (11.9)	44.6 (13.7)	44.2 (12.4)
Sex: Female, Male (Count of Participants)
Female	127 100%	55 100%	182 100%
Male	0 0%	0 0%	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	18 14.2%	4 7.3%	22 12.1%
Not Hispanic or Latino	109 85.8%	51 92.7%	160 87.9%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 0.8%	0 0%	1 0.5%
Asian	1 0.8%	2 3.6%	3 1.6%
Native Hawaiian or Other Pacific Islander	0 0%	1 1.8%	1 0.5%
Black or African American	33 26%	11 20%	44 24.2%
White	92 72.4%	41 74.5%	133 73.1%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	127 100%	55 100%	182 100%

Outcome Measures

1. Primary Outcome

Title	Change in Body Weight
Description	Change in body weight after 12 weeks of treatment with exenatide or placebo twice daily injections. This outcome compares baseline and 12 week body weight.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

subjects randomized to exenatide or placebo

Arm/Group Title	Exenatide	Placebo
Arm/Group Description	Subjects will be randomly assigned to the exenatide study treatment group or to the placebo study treatment group. Exenatide: Subjects will inject 5mcg of exenatide or identically dispensed placebo subcutaneously 15 minutes before the morning and evening meal for the first 2 weeks of the study. At study week 2, subjects will increase to 10mcg twice daily for the remainder of the study.	Subjects will be randomly assigned to the exenatide study treatment group or to the placebo study treatment group. Placebo: Subjects will inject 5mcg of exenatide or identically dispensed placebo subcutaneously 15 minutes before the morning and evening meal for the first 2 weeks of the study. At study week 2, subjects will increase to 10mcg twice daily for the remainder of the study. Dietary counseling: All subjects will also receive individualized dietary counseling. Subjects may or may not be asked to follow a reduced calorie diet in addition to receiving treatment.
Measure Participants	75	33
Mean (Standard Deviation) [percentage weight loss]	6.5 (0.4)	7.5 (0.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Exenatide, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	t-test, 2 sided
	Comments

Adverse Events

Time Frame	Entire study duration, up to 1 year
Adverse Event Reporting Description	Adverse events and serious adverse events are defined according to clinicaltrials.gov definition. Adverse event information was collected at each study visit, in person.
Arm/Group Title	Exenatide		Placebo
Arm/Group Description	Exenatide: Subjects will inject 5mcg of exenatide or identically dispensed placebo subcutaneously 15 minutes before the morning and evening meal for the first 2 weeks of the study. At study week 2, subjects will increase to 10mcg twice daily for the remainder of the study.		Placebo: Subjects will inject 5mcg of exenatide or identically dispensed placebo subcutaneously 15 minutes before the morning and evening meal for the first 2 weeks of the study. At study week 2, subjects will increase to 10mcg twice daily for the remainder of the study. Dietary counseling: All subjects will also receive individualized dietary counseling. Subjects may or may not be asked to follow a reduced calorie diet in addition to receiving treatment.
All Cause Mortality
	Exenatide		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/127 (0%)		0/55 (0%)
Serious Adverse Events
	Exenatide		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/127 (0%)		0/55 (0%)
Other (Not Including Serious) Adverse Events
	Exenatide		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	89/127 (70.1%)		14/55 (25.5%)
Gastrointestinal disorders
nausea	89/127 (70.1%)		14/55 (25.5%)
diarrhea	24/127 (18.9%)		9/55 (16.4%)
vomiting	16/127 (12.6%)		1/55 (1.8%)
reflux	20/127 (15.7%)		9/55 (16.4%)
Metabolism and nutrition disorders
decreased appetite	52/127 (40.9%)		13/55 (23.6%)
Nervous system disorders
headache	34/127 (26.8%)		13/55 (23.6%)
Skin and subcutaneous tissue disorders
rash	14/127 (11%)		1/55 (1.8%)

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.