Acute Metabolic Effects of Melatonin Treatment

NCT03204877 | Completed Phase 1 DMC

• 1 other identifier: Mel06062017
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Glucose Metabolism Disorders

Keywords

Melatonin; Insulin sensitivity; Insulin secretion; Incretin response

Outcome Measures

Primary Outcomes (3)

• Insulin sensitivity

  Insulin sensitivity is assessed by a hyperinsulinemic euglycemic clamp, unit: mg/kg/min

  2 hours (from t= 105 to 225 minutes)

• Insulin secretion

  Insulin secretion is assessed by an intravenous glucose tolerance test, unit: pmol/L (insulin)

  1 hour (from t = 45 to 105 minutes)

• Incretin response

  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 Outcomes (3)

• Inflammatory markers

  Baseline t = -60 minutes and at t = 45 minutes

• Substrate oxidation

  From t=15 minutes to 45 minutes and from t=195 minutes to 225 minutes

• Hormones

  Baseline t = -60 minutes and at t = 45 minutes

Study Arms (2)

Melatonin

ACTIVE COMPARATOR

Four capsules of Melatonin 10 mg is administered orally every hours for four hours during the study day.

Drug: Melatonin

Placebo

PLACEBO COMPARATOR

Four capsules of placebo is administered orally every hours for four hours during the study day.

Other: Placebo

Interventions

Melatonin DRUG

Oral capsules

Melatonin

Placebo OTHER

Oral capsules

Placebo

Eligibility Criteria

• Age: 20 Years - 40 Years
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Aarhus: lead
• University of Copenhagen: collaborator

Study Sites (1)

Aarhus University Hospital

Aarhus, 8000, Denmark

Location

Related Publications (3)

• Pedersen MGB, Lauritzen ES, Svart MV, Stoy J, Sondergaard E, Thomsen HH, Kampmann U, Bjerre M, Jessen N, Moller N, Rittig N. Nutrient sensing: LEAP2 concentration in response to fasting, glucose, lactate, and beta-hydroxybutyrate in healthy young males. Am J Clin Nutr. 2023 Dec;118(6):1091-1098. doi: 10.1016/j.ajcnut.2023.10.007. Epub 2023 Oct 14.

  PMID: 37844838 DERIVED

• Lauritzen ES, Stoy J, Baech-Laursen C, Grarup N, Jessen N, Hansen T, Moller N, Hartmann B, Holst JJ, Kampmann U. The Effect of Melatonin on Incretin Hormones: Results From Experimental and Randomized Clinical Studies. J Clin Endocrinol Metab. 2021 Nov 19;106(12):e5109-e5123. doi: 10.1210/clinem/dgab521.

  PMID: 34265066 DERIVED

• Kampmann U, Lauritzen ES, Grarup N, Jessen N, Hansen T, Moller N, Stoy J. Acute metabolic effects of melatonin-A randomized crossover study in healthy young men. J Pineal Res. 2021 Mar;70(2):e12706. doi: 10.1111/jpi.12706. Epub 2020 Dec 6.

  PMID: 33220095 DERIVED

MeSH Terms

Conditions

Glucose Metabolism Disorders; Insulin Resistance

Interventions

Melatonin

Condition Hierarchy (Ancestors)

Metabolic Diseases; Nutritional and Metabolic Diseases; Hyperinsulinism

Intervention Hierarchy (Ancestors)

Tryptamines; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 6, 2017
• First Posted: July 2, 2017
• Study Start: August 22, 2017
• Primary Completion: February 27, 2019
• Study Completion: February 1, 2020
• Last Updated: March 25, 2020

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)