Obesity
Conditions
Keywords
Obesity, Overweight, Exenatide, Diet, Women
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.
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.
Interventions
DRUGExenatide
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.
DRUGPlacebo
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.
BEHAVIORALDietary counseling
All subjects will also receive individualized dietary counseling. Subjects in the placebo group will be counseled to follow a hypocaloric diet.
Sponsors
AstraZeneca
Jody Dushay
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 70 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| Exenatide 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. | 127 |
| Placebo 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. | 55 |
| Total | 182 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 11 | 3 |
| Overall Study | Lost to Follow-up | 20 | 8 |
| Overall Study | Withdrawal by Subject | 21 | 11 |
Baseline characteristics
| Characteristic | Exenatide | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 43.9 years STANDARD_DEVIATION 11.9 | 44.2 years STANDARD_DEVIATION 12.4 | 44.6 years STANDARD_DEVIATION 13.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 18 Participants | 22 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 109 Participants | 160 Participants | 51 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 33 Participants | 44 Participants | 11 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 92 Participants | 133 Participants | 41 Participants |
| Region of Enrollment United States | 127 participants | 182 participants | 55 participants |
| Sex: Female, Male Female | 127 Participants | 182 Participants | 55 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 127 | 0 / 55 |
| other Total, other adverse events | 89 / 127 | 14 / 55 |
| serious Total, serious adverse events | 0 / 127 | 0 / 55 |
Outcome results
Primary
Change in Body Weight
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
Population: subjects randomized to exenatide or placebo
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Exenatide | Change in Body Weight | 6.5 percentage weight loss | Standard Deviation 0.4 |
| Placebo | Change in Body Weight | 7.5 percentage weight loss | Standard Deviation 0.6 |
p-value: <0.05t-test, 2 sided