Clinical trial NCT01590433: Weight Loss With Exenatide 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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Obesity
Keywords: Obesity
Overweight
Exenatide
Diet
Women
Lead sponsor: Beth Israel Deaconess Medical Center
Sponsor class: OTHER
Collaborators: name: AstraZeneca
First posted: 2012-05-03
Enrollment: 249
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in Body Weight
timeFrame: 12 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
Study officials:
affiliation: Beth Israel Deaconess Medical Center
name: Eleftheria Maratos-Flier, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Rodgers M, Migdal AL, Rodriguez TG, Chen ZZ, Nath AK, Gerszten RE, Kasid N, Toschi E, Tripaldi J, Heineman B, Phan M, Ngo L, Maratos-Flier E, Dushay J. Weight Loss Outcomes Among Early High Responders to Exenatide Treatment: A Randomized, Placebo Controlled Study in Overweight and Obese Women. Front Endocrinol (Lausanne). 2021 Nov 17;12:742873. doi: 10.3389/fendo.2021.742873. eCollection 2021.