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

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.

Study Overview

• Status: Completed
• Conditions: Circadian Rhythm; Melatonin; Glucose; Genes
• Intervention / Treatment: Drug: placebo; Dietary supplement: melatonin

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: melatonin-placebo; subjects will receive melatonin first and placebo second	Drug: placebo; Dietary supplement: melatonin; 5 mg of melatonin per os.
Other: placebo-melatonin; subjects will receive placebo first and melatonin second	Drug: placebo; Dietary supplement: melatonin; 5 mg of melatonin per os.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disposition Index	Disposition index is determined by frequently sampled intravenous glucose tolerance test. It is a composite measure of β-cell function adjusted for insulin sensitivity-was calculated as the product of insulin sensitivity and insulin secretion indices. High value means stronger β-cell function. Theoretical minimum is 0, no theoretical maximum.	During frequently sampled intravenous glucose tolerance test after melatonin/placebo administration on Day 2/4 (melatonin/placebo order randomized) in the laboratory visit

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
First-phase Beta-cell Responsivity	First-phase beta-cell responsivity to glucose is determined by frequently sampled intravenous glucose tolerance test. It likely represents exocytosis of previously primed and docked insulin secretory granules (commonly called the readily releasable pool). It is given by the ratio between the incremental amount of C-peptide secreted during the first phase and the maximum increment of the plasma glucose concentration.High value means stronger β-cell responsivity. Theoretical minimum is 0, no theoretical maximum.	During frequently sampled intravenous glucose tolerance test after melatonin/placebo administration on Day 2/4 (melatonin/placebo order randomized) in the laboratory visit
Insulin Sensitivity	Insulin sensitivity is determined by frequently sampled intravenous glucose tolerance test. It is defined in quantitative terms as the effect of insulin to catalyse the disappearance of glucose from plasma.High value indicates better insulin sensitivity. Theoretical minimum is 0, no theoretical maximum.	During frequently sampled intravenous glucose tolerance test after melatonin/placebo administration on Day 2/4 (melatonin/placebo order randomized) in the laboratory visit
Glucose Tolerance	glucose 3-hour incremental AUC during frequently sampled intravenous glucose tolerance test. High value indicates higher glucose level during the test, which is bad. Theoretical minimum is 0, no theoretical maximum.	During frequently sampled intravenous glucose tolerance test after melatonin/placebo administration on Day 2/4 (melatonin/placebo order randomized) in the laboratory visit

Collaborators and Investigators

• Sponsor: Brigham and Women's Hospital
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Investigators: Principal Investigator: Frank AJL Scheer, PhD, Brigham and Women's Hospital

Study record dates

Study Major Dates

• Study Start: November 1, 2016
• Primary Completion (Actual): March 24, 2022
• Study Completion (Actual): March 24, 2022

Study Registration Dates

• First Submitted: December 21, 2015
• First Submitted That Met QC Criteria: December 28, 2015
• First Posted (Estimated): December 30, 2015

Study Record Updates

• Last Update Posted (Actual): February 12, 2026
• Last Update Submitted That Met QC Criteria: January 26, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indoles; Tryptamines; Melatonin
• Other Study ID Numbers: 2015P000857A; R01DK102696 (U.S. NIH Grant/Contract)