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

This study has been completed.
Sponsor:
Collaborator:
Amylin Pharmaceuticals, LLC.
Information provided by (Responsible Party):
Lisa Kilpatrick, PhD, University of California, Los Angeles
ClinicalTrials.gov Identifier:
NCT01501084
First received: December 20, 2011
Last updated: April 10, 2013
Last verified: April 2013
  Purpose

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.


Condition Intervention
Obesity
Drug: Exenatide
Drug: Normal saline .2cc subcutaneous injection

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: Effects of the GLP-1 Exenatide on Intrinsic Brain Activity in Lean and Obese Women

Resource links provided by NLM:


Further study details as provided by University of California, Los Angeles:

Primary Outcome Measures:
  • Resting State networks in the brain [ Time Frame: one year ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Age and body size differences [ Time Frame: one year ] [ Designated as safety issue: No ]
    The secondary study objective is to determine if/how these changes differ between lean and obese subjects


Enrollment: 34
Study Start Date: December 2011
Study Completion Date: February 2013
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Exenatide
Exenatide injection 10 mcg subcutaneous
Drug: Exenatide
10mcg sc (subcutaneous) injection once at one of the 2 MRI visits
Other Name: Byetta
Placebo Comparator: Saline
.2cc SC injection of sterile normal saline
Drug: Normal saline .2cc subcutaneous injection
sterile saline injection

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 40 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. FEMALES 18 to 40 years of age, inclusive
  2. Lean control subjects with BMI's between 19 and 25kg/m2.
  3. Obese subjects with BMI's between 30 and 35kg/m2.
  4. Willingness to participate in this study as evidenced by a signed, written informed consent form (ICF).
  5. 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.
  6. Negative urine pregnancy tests at all visits.
  7. All subjects must be premenopausal.
  8. In the follicular stage of the menstrual cycle, as determined by menstrual history at Visit 2 &3.
  9. Ambulatory outpatient (not depending exclusively on a wheelchair for mobility)
  10. English is primary oral and written language.
  11. Random (non fasting) Blood sugar level < 200mg/dl at screening.
  12. Right-handed

Exclusion Criteria

  1. Evidence of structural abnormality of the gastrointestinal tract or GI diseases/conditions. Exclusionary GI conditions include but are not limited to: gastrointestinal surgery (exceptions: appendectomy, benign polypectomy, cholecystectomy), pancreatitis, irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), esophagitis (exception: symptom controlled reflux disease), celiac disease, gastrointestinal malignancy or obstruction, functional dyspepsia, peptic ulcer disease, lactose intolerance or any malabsorptive condition.
  2. 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.

  3. 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.
  4. Current history of chronic pain.
  5. Use of investigational drugs, products or devices within 28 days prior to screen and through study participation.
  6. 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.
  7. Subjects who have used diet aids within the last month.
  8. Pregnancy, postpartum within 4 months or breast-feeding
  9. Subjects who smoke more than 5 cigarettes per month.
  10. Subjects with BMI of less than 20, between 26 and 29 and over 35.
  11. Subjects with metal implants, dental retainers, large tattoos (e.g. full arm or back) or claustrophobia; making MRI safety not possible.
  12. Any clinically significant abnormalities from the screening medical history or physical examination.
  13. Subjects who exercise excessively (more than 8 hours a week on average).
  14. Postmenopausal women and/or women who have had oophorectomies.
  15. 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.
  16. Subject taking any medications that might interfere or react badly with the GLP-1 agonist: Exenatide
  17. Subjects with a non-fasting blood glucose level at > 200 dl/ml.
  18. MRI visits with fasting blood sugar < 65 or 126 mg/dl
  19. Left handedness
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01501084

Locations
United States, California
UCLA Gail and Gerald Oppenheimer Family Center for Neurobiology of Stress
LA, California, United States, 90095
Sponsors and Collaborators
University of California, Los Angeles
Amylin Pharmaceuticals, LLC.
Investigators
Study Director: Emeran A Mayer, MD/co-PI Oppenheimer Family Center for Neurobiology of Stress at UCLA
Principal Investigator: Lisa Kilpatrick, PhD Oppenheimer Family Center for Neurobiology of Stress at UCLA
  More Information

No publications provided

Responsible Party: Lisa Kilpatrick, PhD, Principal Investigator, University of California, Los Angeles
ClinicalTrials.gov Identifier: NCT01501084     History of Changes
Other Study ID Numbers: 11-002316
Study First Received: December 20, 2011
Last Updated: April 10, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by University of California, Los Angeles:
functional MRI
Structural MRI
obesity
resting state networks

Additional relevant MeSH terms:
Obesity
Body Weight
Nutrition Disorders
Overnutrition
Overweight
Signs and Symptoms
Exenatide
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Hypoglycemic Agents
Incretins
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 23, 2014