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

NCT01562678 | Completed Phase 4 Results DMC

• 1 other identifier: 2011P000280
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

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

Conditions

Diabetes; Effects of Liraglutide Administration on Brain Activity; Weight Loss; Hunger

Keywords

fMRI; Liraglutide; diabetes; GLP-1

Outcome Measures

Primary Outcomes (1)

• Change Between Highly Desirable vs. Less Desirable Food Cues in the Effect Size of Cortical Activation During Food Visualization

  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

Study Arms (2)

Liraglutide

EXPERIMENTAL

Drug: Liraglutide

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Liraglutide DRUG

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.

Also known as: victoza

Liraglutide

Placebo DRUG

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.

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Lean diabetic:
• Obese diabetic:
• 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.

You may not qualify if:

• Uncontrolled diabetes (HbA1c\>8.9%, or FPG\>250 mg/dL)
• Women who are breastfeeding, pregnant, or wanting to become pregnant.
• Women using IUD
• 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.
• Moderate (creatinine clearance of 30-59 ml/min) and severe renal impairment (creatinine clearance below 30 ml/min) and end-stage renal disease
• Moderate, or severe hepatic impairment
• Hypersensitivity to the active substance or any of the excipients in liraglutide
• History of diabetic ketoacidosis
• Congestive heart failure
• Inflammatory conditions like inflammatory bowel disease, Rheumatoid arthritis etc
• Gastroparesis
• Pancreatitis
• Gallstones- as they may cause increased risk of pancreatitis
• 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.
• Untreated thyroid disease like hypothyroidism or hyperthyroidism

Sponsors & Collaborators

• Beth Israel Deaconess Medical Center: lead

Study Sites (1)

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Related Publications (2)

• Angelidi AM, Kokkinos A, Sanoudou D, Connelly MA, Alexandrou A, Mingrone G, Mantzoros CS. Early metabolomic, lipid and lipoprotein changes in response to medical and surgical therapeutic approaches to obesity. Metabolism. 2023 Jan;138:155346. doi: 10.1016/j.metabol.2022.155346. Epub 2022 Nov 12.

  PMID: 36375643 DERIVED

• 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.

  PMID: 26831302 DERIVED

Related Links

• Mantzoros Lab Website

MeSH Terms

Conditions

Diabetes Mellitus; Weight Loss

Interventions

Liraglutide

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Body Weight Changes; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Glucagon-Like Peptide 1; Glucagon-Like Peptides; Proglucagon; Gastrointestinal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Results Point of Contact

• Title: Dr. Christos Mantzoros
• Organization: Beth Israel Deaconess Medical Center

cmantzor@bidmc.harvard.edu

617-667- 8630

Study Officials

• Christos Mantzoros, MD

  Beth Israel Deaconess Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: March 22, 2012
• First Posted: March 26, 2012
• Study Start: March 1, 2012
• Primary Completion: May 1, 2014
• Study Completion: May 1, 2014
• Last Updated: May 31, 2017
• Results First Posted: May 31, 2017

Record last verified: 2017-04

Locations

US (1)