Acute Metabolic Effects of Melatonin Treatment

March 24, 2020 updated by: University of Aarhus
Modern living is associated with an epidemic of type 2 diabetes mellitus (T2DM). Sleep disturbances are strong independent risk factors for incident diabetes. Melatonin has been implicated in regulation of circadian rhythm and sleep, but it is also ascribed anti-oxidative properties and effects on glucose homeostasis. A potential association between melatonin and T2DM has only been addressed in few human physiological studies, but the topic has received renewed interest since genetic-epidemiological studies have pointed to a role for melatonin in the development of the disease. In the current study, the investigators wish to examine whether treatment with synthetic melatonin induces physiological changes that affect the risk of developing type 2 diabetes. Two studies of the physiological effects of melatonin are included in the present protocol. In study A, the investigators will examine the acute effects of Melatonin on insulin secretion and insulin sensitivity using a Botnia clamp and in study B the investigators will examine the potential effects of Melatonin on the incretin response.

Study Overview

Status

Completed

Intervention / Treatment

Detailed Description

Modern living is associated with an epidemic of type 2 diabetes mellitus (T2DM). Sleep disturbances such as insomnia and frequent awakenings are strong independent risk factors for incident diabetes with a magnitude of effect comparable to a family history of diabetes. Melatonin has been implicated in regulation of circadian rhythm and sleep, but it is also ascribed anti-oxidative properties and effects on glucose homeostasis. In pancreatic islets melatonin have dual effects depending on which signaling pathway is activated by receptor binding, thus both inhibitory and stimulatory effects on insulin secretion have been reported. The effect of melatonin on the secretion of gut hormones such as glucagon-like peptide 1 (GLP-1) and influence of melatonin on beta cell sensitivity to gut hormones is largely unknown, but the presence of the melatonin receptor in the gut suggests that it may have a role. A potential association between melatonin and T2DM has only been addressed in few human physiological studies, but the topic has received renewed interest since genetic-epidemiological studies have pointed to a role for melatonin in the development of the disease. Genetic mutations in the melatonin receptor which is predicted to change the physiological effects of melatonin have been found to increase the risk for T2DM. Additionally, low endogenous melatonin production has been linked to T2DM risk.

The aim of the present study is to examine whether treatment with synthetic melatonin induces physiological changes that affect the risk of developing type 2 diabetes.

Two studies of the physiological effects of melatonin are included in the present protocol:

Study A:

In order to study the acute effects of melatonin administration in healthy men, the investigators aim for assessing whether:

  • Melatonin affects the substrate turn-over as evaluated by indirect calorimetry
  • Melatonin has influence on the ability to secrete insulin as assessed by intravenous glucose tolerance test
  • Melatonin affects the physiological effects of insulin as assessed by use of the hyperinsulinemic euglycemic clamp
  • Genetic mutations in the melatonin receptor gene affect the treatment response to melatonin

Study B:

The investigators aim for examining if melatonin given to healthy men affects the secretion of the glucose-lowering gut hormone glucagon-like peptide 1 (GLP-1) and/or affect the glucose-lowering effects of GLP-1. Specifically, the aim is to assess whether:

  • Melatonin affects the glucose excursions and insulin secretion during an oral glucose tolerance test
  • Melatonin affects the secretion of GLP-1 during an oral glucose tolerance test
  • Melatonin affects the incretin response as assessed by an isoglycemic glucose infusion

Study Type

Interventional

Enrollment (Actual)

36

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Aarhus, Denmark, 8000
        • Aarhus University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

20 years to 40 years (Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

Male

Description

Inclusion Criteria:

  • Male sex
  • Age 20-40 years
  • BMI between 22-30 kg/m2
  • Written consent prior to study participation

Exclusion Criteria:

  • Diabetes or impaired glucose tolerance (fasting p-glucose ≥ 6.1mmol/L)
  • Daily use of a prescription drug
  • Shift work within the last year
  • Travel across >2 time zones in the past three months
  • Use of melatonin on a regular basis within the last year
  • Severe illness
  • High performance athletes
  • Daily tobacco smoking
  • Previous diagnosis of a sleep disorder
  • Present or earlier alcohol or drug abuse
  • Unable to give informed consent
  • Allergy towards melatonin

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Melatonin
Four capsules of Melatonin 10 mg is administered orally every hours for four hours during the study day.
Oral capsules
Placebo Comparator: Placebo
Four capsules of placebo is administered orally every hours for four hours during the study day.
Oral capsules

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Insulin sensitivity
Time Frame: 2 hours (from t= 105 to 225 minutes)
Insulin sensitivity is assessed by a hyperinsulinemic euglycemic clamp, unit: mg/kg/min
2 hours (from t= 105 to 225 minutes)
Insulin secretion
Time Frame: 1 hour (from t = 45 to 105 minutes)
Insulin secretion is assessed by an intravenous glucose tolerance test, unit: pmol/L (insulin)
1 hour (from t = 45 to 105 minutes)
Incretin response
Time Frame: 4 hours (from t = 0 to 240 minutes)
The incretin response is assessed by the difference in incretin hormones between an oral glucose tolerance test and an isoglycemic intravenous glucose infusion, unit: pmol/L (GIP, GLP-1)
4 hours (from t = 0 to 240 minutes)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Inflammatory markers
Time Frame: Baseline t = -60 minutes and at t = 45 minutes
Assessed by blood samples, unit: pg/mL
Baseline t = -60 minutes and at t = 45 minutes
Substrate oxidation
Time Frame: From t=15 minutes to 45 minutes and from t=195 minutes to 225 minutes
Substrate oxidation is assessed by indirect calorimetry. Glucose oxidation: unit: mg/kg/min; protein oxidation: unit: mg/kg/min; lipid oxidation: unit: mg/kg/min
From t=15 minutes to 45 minutes and from t=195 minutes to 225 minutes
Hormones
Time Frame: Baseline t = -60 minutes and at t = 45 minutes
Hormones are assessed by blood samples. Units: C-peptide: pmol/L; Cortisol: ng/mL; Adiponectin: mg/L; IGF-I (ng/ml)
Baseline t = -60 minutes and at t = 45 minutes

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 22, 2017

Primary Completion (Actual)

February 27, 2019

Study Completion (Actual)

February 1, 2020

Study Registration Dates

First Submitted

June 6, 2017

First Submitted That Met QC Criteria

June 28, 2017

First Posted (Actual)

July 2, 2017

Study Record Updates

Last Update Posted (Actual)

March 25, 2020

Last Update Submitted That Met QC Criteria

March 24, 2020

Last Verified

March 1, 2020

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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