Effects of a GLP-1 Receptor Agonist on Functional Activation and Connectivity of the Brain

Study Overview
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Brief Summary
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The aims this study is to explore the effect of a GLP-1 receptor agonist on the degree of brain activation and connectivity obtained by functional magnetic resonance imaging in lean and obese type 2 diabetes

Detailed Description
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Fifteen lean [BMI(body mass index) less than 23 kg/m2] type 2 diabetes subjects and fifteen obese (BMI more than 26 kg/m2) subjects with type 2 diabetes treated by diet and/or metformin, SU(sulfonylurea), DPP4-inhibitors(Dipeptidyl peptidase-4 inhibitor) will be recruited. Every subject will be studied on 2 separate days in random order with 1-2 week intervals. These participants will be injected either normal saline or 10 mcg of lixisenatide in a cross-over fashion. Neuroimaging composed with resting-12-min, visual stimulation task-12-min, T1-5-min, and diffusion tensor image-12-min will be proceeded. Ad lib buffet will be provided to every participant and the intake will be measured. Surveys about appetite and mood will be done before and after neuroimaging test and buffet eating.

Official Title
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Effects of a GLP-1 Receptor Agonist on Functional Activation and Connectivity of the Brain Measured by Functional MRI

Conditions
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Diabetes Mellitus

Intervention / Treatment
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* Drug: Lixisenatide
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: BMI ≤ 23kg/m2 or BMI ≥ 26kg/m2 participants with diabetes treated by diet or oral antidiabetic drug, HbA1c less than 8.5% Exclusion Criteria: Those who diagnosed by Type 1 diabetes History of insulin therapy Aspartate aminotransferase(AST) or Alanine transaminase(ALT) >2.5 times of upper normal reference range Estimated Glomerular Filtration Rate(eGFR) <30 mL/min/1.73m2 Those who can't be performed MRI

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lixisenatide injection<br>intervention : Lyxumia® pen injection 10 microgram (Lixisenatide) subcutaneous injection 30 minutes before functional MRI | Drug: Lixisenatide<br>* Colorless, transparent liquid contained in a glass prefilled syringe pen-like injection (GLP-1 receptor agonist)<br>* Other names: Lyxumia® pen injection;|
| Placebo Comparator: Normal saline<br>control : normal saline 0.3 cc subcutaneous injection before functional MRI | Other: Placebo<br>* Normal saline injection before performing fMRI<br>* Other names: Normal saline injection;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference of BOLD (Blood oxygenation level-dependent) signal in hypothalamus |  | 10min (40 min after injection) | 
| Whole brain connectivity |  | 20min (50 min after injection) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| appetite change | Visual analoge scale-questionnaire consisting of 8 questions (Flint, Raben, Blundell, & Astrup, 2000) | -30min, 45min(after fMRI), 70min(after buffet) | 
| mood change | Visual analoge scale-questionnaire consisting of 16 questions (Boggieo et al., 2008) | -30min, 45min(after fMRI), 70min(after buffet) | 
| intake of food in the buffet | It will be provided quantified juice and milk , boiled eggs, bread , bananas and chocolate bars. Participants may eat freely for 20 minutes. Then measure the intake of participants. Compares whether the difference in food intake pattern . | 50min | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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lean/obese diabetes mellitus, functional MRI, GLP-1, appetite, activation of brain, connectivity