- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03204877
Acute Metabolic Effects of Melatonin Treatment
Study Overview
Status
Conditions
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
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
-
-
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Aarhus, Denmark, 8000
- Aarhus University Hospital
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
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
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.
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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)
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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
Sponsor
Collaborators
Publications and helpful links
General Publications
- 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.
- 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.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- Mel06062017
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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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