Interaction of Melatonin and MTNR1B Genotype on Glucose Control - Study 1

Study Overview
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Brief Summary
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This project aims to test the impact of melatonin and MTNR1B variation on regulation glucose regulation in a highly controlled in-laboratory setting and ex vivo in pancreatic islets.

Detailed Description
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The investigators' recent GWAS discovery of MTNR1B as a novel type 2 diabetes gene has sparked great interest into the role of melatonin in glycemic control, for which the mechanism is largely unknown. This research will determine the effect of melatonin and MTNR1B on glycemic control under highly-controlled, in-laboratory protocols while manipulating circulating melatonin concentrations (both up and down) and assessing glycemic control by frequently-sampled intravenous glucose tolerance tests, as well as in ex vivo human pancreatic islets. This research will provide mechanistic insights into the metabolic effects of melatonin and the MTNR1B risk variant and may help in evidence-based approaches and personalized recommendations to improve glycemic control in night shift workers and late-night eaters.

Official Title
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Interaction of Melatonin and MTNR1B Genotype on Glucose Control - Study 1

Conditions
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Glucose, Circadian Rhythm, Melatonin, Genes

Intervention / Treatment
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* Dietary Supplement: melatonin
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Body Mass Index: 20 and 35 kg/m2 Age: 21-55 years of age Caucasian Non-smoking With regular sleep-wake cycle Passed medical and psychological screening tests Exclusion Criteria: Acute, chronic or debilitating medical conditions History of neurological or psychiatric disorder History of sleep disorder or regular use of sleep-promoting medication Current prescription, herbal, or over-the-counter medication use Traveling across 2 or more time zones within past 3 months Worked night or rotating shift work within past 1 year Drug or alcohol dependency

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: melatonin-placebo<br>subjects will receive melatonin first and placebo second | Dietary Supplement: melatonin<br>* 5 mg of melatonin per os.<br>Drug: placebo<br> <br> |
| Other: placebo-melatonin<br>subjects will receive placebo first and melatonin second | Dietary Supplement: melatonin<br>* 5 mg of melatonin per os.<br>Drug: placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change in disposition index | Disposition index will be determined by frequently sampled intravenous glucose tolerance test | Day 2 and/or 4 of the in-lab protocol | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change in first-phase insulin release |  | Day 2, 3, 4 and/or 5 of the in-lab protocol | 
| change in insulin sensitivity |  | Day 2, 3, 4 and/or 5 of the in-lab protocol | 
| change in glucose tolerance |  | Day 2, 3, 4 and/or 5 of the in-lab protocol |