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

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2013 by Beth Israel Deaconess Medical Center
Sponsor:
Information provided by (Responsible Party):
Beth Israel Deaconess Medical Center
ClinicalTrials.gov Identifier:
NCT01562678
First received: March 22, 2012
Last updated: February 19, 2013
Last verified: February 2013
  Purpose

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.

Condition Intervention
Diabetes
Effects of Liraglutide Administration on Brain Activity
Weight Loss
Hunger
Drug: Liraglutide
Drug: Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Basic Science
Official Title: Liraglutide in Obesity and Diabetes: Identification of CNS Targets Using fMRI

Resource links provided by NLM:


Further study details as provided by Beth Israel Deaconess Medical Center:

Primary Outcome Measures:
  • Difference in brain activation between Liraglutide treatment and placebo. [ Time Frame: 18 days of Liraglutide or placebo treatment ] [ Designated as safety issue: No ]

Estimated Enrollment: 24
Study Start Date: March 2012
Estimated Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: victoza
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.

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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  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: NCT01562678

Contacts
Contact: Christos S Mantzoros, MD 617-667-8630 mantzlab@bidmc.harvard.edu

Locations
United States, Massachusetts
Beth Israel Deaconess Medical Center Recruiting
Boston, Massachusetts, United States, 02215
Contact: Christos S Mantzoros, MD    617-667-8630    mantzlab@bidmc.harvard.edu   
Principal Investigator: Christos S Mantzoros, MD         
Sponsors and Collaborators
Beth Israel Deaconess Medical Center
Investigators
Principal Investigator: Christos Mantzoros, MD Beth Israel Deaconess Medical Center
  More Information

Additional Information:
No publications provided

Responsible Party: Beth Israel Deaconess Medical Center
ClinicalTrials.gov Identifier: NCT01562678     History of Changes
Other Study ID Numbers: 2011-P000280
Study First Received: March 22, 2012
Last Updated: February 19, 2013
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Beth Israel Deaconess Medical Center:
fMRI
Liraglutide
diabetes
GLP-1

Additional relevant MeSH terms:
Diabetes Mellitus
Weight Loss
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Body Weight Changes
Body Weight
Signs and Symptoms
Glucagon-Like Peptide 1
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 24, 2014