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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:
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:
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Liraglutide | Experimental |
| |
| Placebo | Placebo Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
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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:
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| Name | Affiliation | Role |
|---|---|---|
| Christos Mantzoros, MD | Beth Israel Deaconess Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Beth Israel Deaconess Medical Center | Boston | Massachusetts | 02215 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 36375643 | Derived | 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. | |
| 26831302 | Derived |
| Label | URL |
|---|---|
| Mantzoros Lab Website | View source |
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| ID | Title | Description |
|---|---|---|
| FG000 | Liraglutide First, Then Placebo | 14 participants were randomized to receive Liraglutide and then were cross-overed to receive placebo |
| FG001 | Placebo First, Then Liraglutide | 14 participants were randomized to receive Placebo and then were cross-overed to receive Liraglutide |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Liraglutide First, Then Placebo | 14 participants were randomized to receive Liraglutide and then were cross-overed to receive placebo |
| BG001 | Placebo First, Then Liraglutide | 14 participants were randomized to receive Placebo and then were cross-overed to receive Liraglutide |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Participants with incomplete MRI scans were excluded from the analysis. | Posted | Mean | Standard Error | z-scores of activation in cortex | 18 days of Liraglutide or placebo treatment |
|
Throughout the study (4 visits in each phase of liraglutide and placebo).
There was a systematic assessment of adverse events at each visit (Days 0, 7, 14, and 17) by an MD who asked detailed medical questions and did a physical exam, plus through the use of visual analog scales administered 3 times per day where participants answered on a 10cm line questions such as "How nauseous do you feel right now?"
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Liraglutide | 14 participants were randomized to receive Liraglutide and then were cross-overed to receive placebo and 14 participants were randomized to receive Placebo and then were cross-overed to receive Liraglutide |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Christos Mantzoros | Beth Israel Deaconess Medical Center | 617-667- 8630 | cmantzor@bidmc.harvard.edu |
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| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D015431 | Weight Loss |
| ID | Term |
|---|---|
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D004700 | Endocrine System Diseases |
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| ID | Term |
|---|---|
| D000069450 | Liraglutide |
| ID | Term |
|---|---|
| D052216 | Glucagon-Like Peptide 1 |
| D004763 | Glucagon-Like Peptides |
| D052336 | Proglucagon |
| D005768 | Gastrointestinal Hormones |
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|
|
| 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. |
|
| 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. |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG001 | Placebo | Placebo: In the placebo phase 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. Participants had this first or second (liraglutide was the other phase). |
|
|
| 0 |
| 28 |
| 7 |
| 28 |
| EG001 | Placebo | 14 participants were randomized to receive Placebo and then were cross-overed to receive Liraglutide and 14 participants were randomized to receive Liraglutide and then were cross-overed to receive placebo | 0 | 28 | 7 | 28 |
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| D001836 | Body Weight Changes |
| D001835 | Body Weight |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D006728 |
| Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |