Weight Loss With Exenatide Treatment

Phase 4

Completed

Conditions: Obesity

Interventions: Drug: Placebo
Drug: Exenatide
Behavioral: Dietary counseling

Registration Number: NCT01590433

Lead Sponsor: Jody Dushay

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 249

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Dietary counseling	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.
Placebo	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.
Exenatide	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.

Primary Outcome Measures

Name	Time	Method
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.

Secondary Outcome Measures