Liraglutide in Obesity and Diabetes: Identification of CNS Targets Using fMRI

April 26, 2017 updated by: Christos Mantzoros, Beth Israel Deaconess Medical Center

The main purpose of this study is to help us understand the effects of diabetes medication Liraglutide on weight loss and hunger. The investigators have already determined what the highest tolerated dose of Liraglutide is through earlier human research studies. Liraglutide was approved by the FDA in January 2010 for treatment of diabetes.

The investigators will also study the following:

  1. The impact of Liraglutide on brain responses to food
  2. It's effect on physiological and mental performance
  3. If its effect on the brain differs among obese and lean diabetic subjects.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This is a randomized, placebo controlled, cross-over, double-blinded study to assess the effects of liraglutide on brain activation in areas involved in cognitive control and reward during food visualization.

Study participation will span approximately 1.5-2 months. Subjects will learn to self-administer the medication and will have a total of 8 study visits plus one screening visit. The visits will include the following tests/procedures:

  1. Vital signs (blood pressure, temperature, heart rate, breathing rate)
  2. Height, weight and other body measurements like waist
  3. Blood tests
  4. Urine pregnancy test (women only)
  5. Electrocardiogram (EKG)
  6. Medical history
  7. Physical exam
  8. Body Composition tests
  9. Study logs to record food intake and blood sugar
  10. functional MRI

We plan to recruit a total of 24 subjects to be treated with placebo and liraglutide. We propose to enroll 12 obese diabetic (type 2) and 12 lean diabetic (type 2) subjects. Equal numbers of men and women will be enrolled and the randomization will block for gender.

Study Type

Interventional

Enrollment (Actual)

28

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Beth Israel Deaconess Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

Subjects will be men and women between the ages of 18 and 65. The following table list inclusion criteria for each group (lean diabetic and obese diabetic). Subjects must meet either HbA1c or fasting plasma glucose (FPG) criteria.

Lean diabetic:

BMI: 18-25 kg/m2 HbA1c: < 8.9% Fasting plasma glucose: <250 mg/dL Other inclusion criteria: On dietary modification and/or metformin

Obese diabetic:

BMI: >27 kg/m2 HbA1c: < 8.9% Fasting plasma glucose: <250 mg/dL Other inclusion criteria: On dietary modification and/or metformin

Additionally, women participants must use double barrier methods to prevent pregnancy (diaphragm with intravaginal spermicide, cervical cap, male or female condom with spermicide). If a woman suspects that she has become pregnant at any time or does not use one of the contraceptive methods recommended by the investigator, she must notify the study staff. If a woman becomes pregnant, she will be withdrawn from the study. The study staff will follow the progress of her pregnancy and the birth of her child.

Exclusion Criteria:

  1. Uncontrolled diabetes (HbA1c>8.9%, or FPG>250 mg/dL)
  2. Women who are breastfeeding, pregnant, or wanting to become pregnant.
  3. Women using IUD
  4. Any change in the dosage of hormonal contraceptive medications (birth control pills, implanon). Subjects should remain on same medication/ same dose during the time of the entire study.
  5. Moderate (creatinine clearance of 30-59 ml/min) and severe renal impairment (creatinine clearance below 30 ml/min) and end-stage renal disease
  6. Moderate, or severe hepatic impairment
  7. Hypersensitivity to the active substance or any of the excipients in liraglutide
  8. History of diabetic ketoacidosis
  9. Congestive heart failure
  10. Inflammatory conditions like inflammatory bowel disease, Rheumatoid arthritis etc
  11. Gastroparesis
  12. Pancreatitis
  13. Gallstones- as they may cause increased risk of pancreatitis
  14. Alcohol consumption- the maximum quantity for men is 140g-210g per week. For women, the range is 84g-140g per week or drinking as consuming no more than two drinks a day for men and one for women. Alcohol can cause increased risk of pancreatitis and hypoglycemia.
  15. Untreated thyroid disease like hypothyroidism or hyperthyroidism
  16. Subjects taking the following medications: warfarin, steroids (inhaled or systemic due to reduced hypoglycemic effect), and subjects on other hormones (LHRH analogs etc).
  17. Subjects on any oral anti-diabetic agent except metformin
  18. Personal or family history of MEN II or medullary thyroid cancer
  19. Subjects with any type of bioimplant activated by mechanical, electronic, or magnetic means (e.g. cochlear implants, pacemakers, neuron or biostimulators, electronic infusion pumps, etc.)
  20. Subjects with any type of metallic implant that could potentially be displaced or damaged during MRI, such as aneurysm clips, metallic skull plates, surgical implants etc. or metal containing tattoos
  21. Anxiety and/or claustrophobia
  22. Uncontrolled cardiac impairment, circulatory impairment, or inability to perspire (poor thermoregulatory function)
  23. Significant sensory or motor impairment
  24. Epilepsy, particularly photo-sensitive epilepsy, which may place the individual at a higher risk for adverse events during fMRI scanning with visual stimulation
  25. Subjects with neurological problems which may interfere with or complicate testing (e.g. presence of titubation)
  26. Body weight above the limitation of the MRI scanning table (330lbs/150 Kg) or body dimensions that could difficult the performance of the scan.
  27. Subjects who cannot adhere to the experimental protocol for any reason
  28. Anemia with Hgb less than 10
  29. Uncontrolled infectious diseases (e.g. HIV, hepatitis, chronic infections etc)
  30. Any uncontrolled endocrine condition, e.g Cushing's, Acromegaly, etc
  31. Any cancers or lymphoma
  32. Eating disorders like anorexia, bulimia
  33. Severe hypertriglyceridemia (triglycerides >500 mg/dl)
  34. Weight loss surgery or gastrectomy
  35. Any changes in medications that affect brain function, e.g. anti-depressants, anti-psychotics, anti-anxiety, anti-seizure medications, antihypertensives etc (subjects should remain on same medication/ same dose during the time of the entire study).
  36. Irregular periods, defined as cycle length less than 22 days or more than 40 days.
  37. Any change in smoking status.
  38. Vegetarians- as food images presented will include numerous non-vegetarian items and thus will not be appealing as high calorie food items.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
Drug: Placebo
In the placebo arm of this randomized, placebo controlled, cross-over, double-blinded study to assess the effects of liraglutide. Subjects will self-inject placebo once per day for 18 days.
Experimental: Liraglutide
Drug: Liraglutide
In the experimental arm of this randomized, placebo controlled, cross-over, double-blinded study to assess the effects of liraglutide. Subjects will self-inject Liraglutide once per day for 18 days. Subjects will start the treatment with a dose of 0.6 mg for the first week, then 1.2 mg for the second week and 1.8 mg for 3 days in the third week.
Other Names:
  • victoza

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change Between Highly Desirable vs. Less Desirable Food Cues in the Effect Size of Cortical Activation During Food Visualization
Time Frame: 18 days of Liraglutide or placebo treatment
Effect size (region of interest z-scores, derived from z-maps of the brain) shown below is the difference in parietal cortex activation to highly desirable (high fat or high calorie, e.g. cakes, pies, fries) versus less desirable (low fat or low calorie, e.g. vegetables, fruits) food cues for each treatment condition (liraglutide or placebo) at the end of the treatment period.
18 days of Liraglutide or placebo treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Beth Israel Deaconess Medical Center

Investigators

  • Principal Investigator: Christos Mantzoros, MD, Beth Israel Deaconess Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2012

Primary Completion (Actual)

May 1, 2014

Study Completion (Actual)

May 1, 2014

Study Registration Dates

First Submitted

March 22, 2012

First Submitted That Met QC Criteria

March 23, 2012

First Posted (Estimate)

March 26, 2012

Study Record Updates

Last Update Posted (Actual)

May 31, 2017

Last Update Submitted That Met QC Criteria

April 26, 2017

Last Verified

April 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2011P000280

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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