Weight Loss With Exenatide Treatment

NCT ID: NCT01590433

Last Updated: 2021-06-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 249 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-03-31
• Study Completion Date: 2019-01-31

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.

Conditions

Obesity

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

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.

Group Type: EXPERIMENTAL

Exenatide

Intervention Type: DRUG

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

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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.

Dietary counseling

Intervention Type: BEHAVIORAL

All subjects will also receive individualized dietary counseling. Subjects in the placebo group will be counseled to follow a hypocaloric diet.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Dietary counseling

All subjects will also receive individualized dietary counseling. Subjects in the placebo group will be counseled to follow a hypocaloric diet.

Intervention Type: BEHAVIORAL

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

AstraZeneca

INDUSTRY

Sponsor Role: collaborator

Jody Dushay

OTHER

Sponsor Role: lead

Responsible Party

Jody Dushay

Assistant Professor of Medicine

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Eleftheria Maratos-Flier, MD

Role: PRINCIPAL_INVESTIGATOR

Beth Israel Deaconess Medical Center

Locations

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 34867786 (View on PubMed)

Provided Documents

Document Type: Study Protocol, Statistical Analysis Plan, and Informed Consent Form

View Document

Other Identifiers

2011P000310

Identifier Type: -

Identifier Source: org_study_id