Liraglutide in Obesity and Diabetes: Identification of CNS Targets Using fMRI
Condition: Diabetes; Effects of Liraglutide Administration on Brain Activity; Weight Loss; Hunger
MeSH terms: Diabetes Mellitus; Weight Loss
Intervention: Liraglutide; Placebo
Intervention description: 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.; 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.
Intervention MeSH terms: Liraglutide
Phase: Phase 4
Study type: Interventional
Primary purpose: Basic Science
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 28.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: fMRI; Liraglutide; diabetes; GLP-1

Summary:

      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.
    

Eligibility 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.