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

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ClinicalTrials.gov Identifier: NCT01562678
Recruitment Status : Completed
First Posted : March 26, 2012
Results First Posted : May 31, 2017
Last Update Posted : May 31, 2017
Sponsor:
Information provided by (Responsible Party):
Christos Mantzoros, Beth Israel Deaconess Medical Center

Tracking Information
First Submitted Date  ICMJE March 22, 2012
First Posted Date  ICMJE March 26, 2012
Results First Submitted Date  ICMJE December 22, 2015
Results First Posted Date  ICMJE May 31, 2017
Last Update Posted Date May 31, 2017
Study Start Date  ICMJE March 2012
Actual Primary Completion Date May 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 26, 2017)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: March 23, 2012)
Difference in brain activation between Liraglutide treatment and placebo. [ Time Frame: 18 days of Liraglutide or placebo treatment ]
Change History Complete list of historical versions of study NCT01562678 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Liraglutide in Obesity and Diabetes: Identification of CNS Targets Using fMRI
Official Title  ICMJE Liraglutide in Obesity and Diabetes: Identification of CNS Targets Using fMRI
Brief 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.
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  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Basic Science
Condition  ICMJE
  • Diabetes
  • Effects of Liraglutide Administration on Brain Activity
  • Weight Loss
  • Hunger
Intervention  ICMJE
  • 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
  • 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.
Study Arms  ICMJE
  • Experimental: Liraglutide
    Intervention: Drug: Liraglutide
  • Placebo Comparator: Placebo
    Intervention: Drug: Placebo
Publications * Farr OM, Sofopoulos M, Tsoukas MA, Dincer F, Thakkar B, Sahin-Efe A, Filippaios A, Bowers J, Srnka A, Gavrieli A, Ko BJ, Liakou C, Kanyuch N, Tseleni-Balafouta S, Mantzoros CS. GLP-1 receptors exist in the parietal cortex, hypothalamus and medulla of human brains and the GLP-1 analogue liraglutide alters brain activity related to highly desirable food cues in individuals with diabetes: a crossover, randomised, placebo-controlled trial. Diabetologia. 2016 May;59(5):954-65. doi: 10.1007/s00125-016-3874-y. Epub 2016 Feb 1.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 26, 2017)
28
Original Estimated Enrollment  ICMJE
 (submitted: March 23, 2012)
24
Actual Study Completion Date  ICMJE May 2014
Actual Primary Completion Date May 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01562678
Other Study ID Numbers  ICMJE 2011P000280
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Christos Mantzoros, Beth Israel Deaconess Medical Center
Study Sponsor  ICMJE Beth Israel Deaconess Medical Center
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Christos Mantzoros, MD Beth Israel Deaconess Medical Center
PRS Account Beth Israel Deaconess Medical Center
Verification Date April 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP