Effects of the GLP-1 Exenatide on Satiety in Lean and Obese Women

NCT01501084 | Completed Phase 1

• 1 other identifier: 11-002316
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

Brief Summary

Obesity is a major health problem in the US and many Western countries, with more than half of the population being overweight or obese. Yet, despite intense research efforts into the mechanisms underlying obesity and into the development of novel pharmacologic interventions, bariatric surgery, including gastric bypass surgery is the only successful treatment for severe obesity. Mimicking one of the effects of bariatric surgery, e.g. the increased secretion of glucagon-like peptide 1 (GLP-1) could be an effective strategy against obesity. Obese individuals may be more sensitive to the rewarding aspects of food and less responsive to signals from the gut about actual energy needs. Using functional MRI scanning the investigators plan to examine the effect of Exenatide (a GLP-1 analog known to reduce caloric intake and produce weight loss in both obese and lean individuals) on activity within brain regions/networks involved in reward/motivation and in regulation of energy requirements. The investigators expect the peptide to change the balance between desire to eat for pleasure and the need to eat to maintain homeostasis.

Conditions

Obesity

Keywords

functional MRI; Structural MRI; obesity; resting state networks

Outcome Measures

Primary Outcomes (1)

• Resting State networks in the brain

  The proposed study aims to address two important questions regarding the mechanisms underlying the weight loss associated with exenatide. Our primary study objective is to determine whether Exenatide changes the resting state activity of the brain, and alters the connectivity between brain regions involved in homeostatic and hedonic brain circults.

  one year

Secondary Outcomes (1)

• Age and body size differences

  one year

Study Arms (2)

Exenatide

ACTIVE COMPARATOR

Exenatide injection 10 mcg subcutaneous

Drug: Exenatide

Saline

PLACEBO COMPARATOR

.2cc SC injection of sterile normal saline

Drug: Normal saline .2cc subcutaneous injection

Interventions

Exenatide DRUG

10mcg sc (subcutaneous) injection once at one of the 2 MRI visits

Also known as: Byetta

Exenatide

Normal saline .2cc subcutaneous injection DRUG

sterile saline injection

Saline

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• FEMALES 18 to 40 years of age, inclusive
• Lean control subjects with BMI's between 19 and 25kg/m2.
• Obese subjects with BMI's between 30 and 35kg/m2.
• Willingness to participate in this study as evidenced by a signed, written informed consent form (ICF).
• Willingness to avoid pregnancy and practice adequate birth control (abstinence, oral contraception, intrauterine devices, implantable devices, or barrier method with spermicide) during the time of study enrollment.
• Negative urine pregnancy tests at all visits.
• All subjects must be premenopausal.
• In the follicular stage of the menstrual cycle, as determined by menstrual history at Visit 2 \&3.
• Ambulatory outpatient (not depending exclusively on a wheelchair for mobility)
• English is primary oral and written language.
• Random (non fasting) Blood sugar level \< 200mg/dl at screening.
• Right-handed

You may not qualify if:

• Clinical evidence of cardiovascular, respiratory, renal, hepatic, malignancy, hematologic, neurologic (including regular migraines defined as more than 1 migraine per month), psychiatric or any disease that the PI determines may interfere with safe participation in the study.
• \* Very specifically subjects with any history or symptoms of poor glucose control, osteoporosis, diabetes, thyroid, adrenal or other endocrine disorder.
• Subjects with current psychiatric disorder, or history of such disorder in the past 5 years. This list includes but is not limited to bipolar disorder, alcohol or substance abuse/dependence, suicide attempt or behavior, or presence of anxiety or depression at the time of screening. Poorly controlled anxiety or depression will be determined as a result of MINI + interview by the clinician at screening.
• Current history of chronic pain.
• Use of investigational drugs, products or devices within 28 days prior to screen and through study participation.
• Subjects with current use of any medications/drugs during the study that affect the central nervous system, gastrointestinal motility, autonomic activity or pain sensation, including but not limited to: opiates or other narcotic analgesics, THC, alpha adrenergic receptor antagonists, beta blockers, Ca+ blockers, prokinetics and sympatholytic agents, or antidepressants.
• Subjects who have used diet aids within the last month.
• Pregnancy, postpartum within 4 months or breast-feeding
• Subjects who smoke more than 5 cigarettes per month.
• Subjects with BMI of less than 20, between 26 and 29 and over 35.
• Subjects with metal implants, dental retainers, large tattoos (e.g. full arm or back) or claustrophobia; making MRI safety not possible.
• Any clinically significant abnormalities from the screening medical history or physical examination.
• Subjects who exercise excessively (more than 8 hours a week on average).
• Postmenopausal women and/or women who have had oophorectomies.
• Any other condition that the investigator believes would jeopardize the safety or rights of the subject or would render the subject unable to comply with the study protocol.

Sponsors & Collaborators

• University of California, Los Angeles: lead
• Amylin Pharmaceuticals, LLC.: collaborator

Study Sites (1)

UCLA Gail and Gerald Oppenheimer Family Center for Neurobiology of Stress

Los Angeles, California, 90095, United States

Location

MeSH Terms

Conditions

Obesity

Interventions

Exenatide

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Peptides; Amino Acids, Peptides, and Proteins; Venoms; Complex Mixtures; Toxins, Biological; Biological Factors

Study Officials

• Emeran A Mayer, MD/co-PI

  Oppenheimer Family Center for Neurobiology of Stress at UCLA

  STUDY DIRECTOR

• Lisa Kilpatrick, PhD

  Oppenheimer Family Center for Neurobiology of Stress at UCLA

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 20, 2011
• First Posted: December 29, 2011
• Study Start: December 1, 2011
• Primary Completion: December 1, 2012
• Study Completion: February 1, 2013
• Last Updated: November 7, 2017

Record last verified: 2017-11

Data Sharing

• IPD Sharing: Will share

Locations

US (1)