Metabolic Effects of Melatonin Treatment

NCT03859934 | Completed Phase 1 DMC

• 1 other identifier: 2019-000213-37
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

Modern living is associated with an epidemic of type 2 diabetes mellitus (T2DM). Sleep disturbances such as insomnia or frequent awakenings are strong risk factors for T2DM with several studies indicating a central role of melatonin. Additionally, a certain single nucleotide polymorphism in the melatonin receptor gene, MTNR1B rs10830963, with an allele frequency of 30 %, is associated with increased fasting plasma glucose and T2DM. Due to treatment of, among other things, insomnia, the use of melatonin is increasing rapidly in Denmark with a 100-fold increase from 2007-2012 in children and adolescents. No previous studies have thoroughly assessed changes in glucose and fatty acid metabolism after 3 months of melatonin treatment in patients with T2DM.

Conditions

Metabolic Disease; Insulin Sensitivity; Glucose Metabolism Disorders (Including Diabetes Mellitus); Type 2 Diabetes Mellitus; Blood Pressure; Inflammation

Outcome Measures

Primary Outcomes (4)

• Change of insulin sensitivity

  Insulin sensitivity is assessed by a hyperinsulinemic euglycemic clamp, unit: mg/kg/min (mg of glucose to maintain euglycemia per kilogram of weight per minuts)

  The outcome will be measured after 3 months of placebo treatment and after 3 months of melatonin treatment and compared afterwards with a paired T-tes

• Change of insulin secretion change

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

  The outcome will be measured after 3 months of placebo treatment and after 3 months of melatonin treatment

• MTNR1a rs10830963 influence on change in insulin sensitivity and insulin secretion

  MTNR1a rs10830963 genotype influence on insulin sensitivity and insulin secretion (see outcome 1 + 2)

  The outcome will be measured after 3 months of placebo treatment and again after 3 months of melatonin treatment

• Change of insulin signalling

  Insulin signalling in muscle and adipose tissue assessed by western blot

  The outcome will be measured after 3 months of placebo treatment and after 3 months of melatonin treatment

Secondary Outcomes (13)

• Change of ambulatory blood pressure

  The outcome will be measured after 3 months of placebo treatment and after 3 months of melatonin treatment

• Change of arterial stiffness

  The outcome will be measured after 3 months of placebo treatment and after 3 months of melatonin treatment

• Change of gut microbiome

  The outcome will be measured after 3 months of placebo treatment and after 3 months of melatonin treatment

• Change of sleep evaluation 1

  The outcome will be measured after 3 months of placebo treatment and after 3 months of melatonin treatment

• Change of sleep evaluation 2

  After 3 months treatmentThe outcome will be measured after 3 months of placebo treatment and after 3 months of melatonin treatment

Study Arms (2)

Melatonin

ACTIVE COMPARATOR

10 mg melatonin each day 1 hour before bedtime for 3 months

Drug: Melatonin

Placebo

PLACEBO COMPARATOR

Placebo each day 1 hour before bedtime for 3 months

Drug: Placebo Oral Tablet

Interventions

Melatonin DRUG

Melatonin treatment

Also known as: Melatonin treatment

Melatonin

Placebo Oral Tablet DRUG

Placebo treatment

Also known as: Placebo treatment

Placebo

Eligibility Criteria

• Age: 40 Years - 70 Years
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male sex
• Caucasian race
• Type 2 Diabetes Mellitus (T2DM)
• T2DM duration of maximum 20 years
• Age 40-70 years
• BMI between 25-35 kg/m2 at T2DM debut
• Written consent prior to study participation

You may not qualify if:

• \> 3 daily antihypertensive drugs
• Blood pressure \> 160/100 mmHg
• Insulin treatment
• \> 3 daily oral antidiabetic drugs
• \> 1 lipid lowering drug
• HbA1c \> 65
• Heart failure (New York Heart Association Class III or IV), liver disease (alanine aminotransferase (ALAT) \> twice the upper limit of normal serum concentration), plasma creatinine \> 130 µmol/L and/or albuminuria, goiter, active cancer, acute or chronic pancreatitis
• Treatment with antidiabetic medicine that cannot be paused on study days (or for a week if the participants is treated with longtime-acting GLP-1 analogs)
• Shift work within the last year
• Travel across \>4 time zones planned within the next 6 months
• Use of melatonin on a regular basis within the last year
• Severe illness
• \> 14 units of alcohol/week
• Previous diagnosis of a sleep disorder
• Present or earlier alcohol or drug abuse

Sponsors & Collaborators

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

Study Sites (1)

Medical Research Laboratory

Aarhus, 8200, Denmark

Location

MeSH Terms

Conditions

Metabolic Diseases; Insulin Resistance; Glucose Metabolism Disorders; Diabetes Mellitus, Type 2; Inflammation

Interventions

Melatonin

Condition Hierarchy (Ancestors)

Nutritional and Metabolic Diseases; Hyperinsulinism; Diabetes Mellitus; Endocrine System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

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

Study Officials

• Esben Stistrup Lauritzen, MD

  Medical Research Laboratory

  PRINCIPAL INVESTIGATOR

• Ulla Kampmann Opstrup, MD, PhD

  Aarhus University Hospital

  PRINCIPAL INVESTIGATOR

• Julie Støy, MD, PhD

  Aarhus University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

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

Model Details: Randomized, placebo controlled, double blinded crossover study

Study Record Dates

• First Submitted: February 18, 2019
• First Posted: March 1, 2019
• Study Start: September 26, 2019
• Primary Completion: May 3, 2021
• Study Completion: August 18, 2021
• Last Updated: August 25, 2021

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)