Metabolic DiseasePhase 1NCT03859934
Metabolic Effects of Melatonin Treatment
A Phase 1 study testing Melatonin in people with Metabolic Disease and Insulin Sensitivity, run by University of Aarhus at 1 site in Denmark.
Trial 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. Read more about this study
- Who is it for?
- Ages 40 to 70 years, men only
- Conditions the study is for
- Metabolic Disease, Insulin Sensitivity, Glucose Metabolism Disorders (Including Diabetes Mellitus)
- What is being tested?
- Melatonin
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 17 participants
- Where
- 1 siteDenmark
- Study dates
- 26 Sep 2019to 18 Aug 2021
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 70 years
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- > 3 daily antihypertensive drugs
- Blood pressure > 160/100 mmHg
- Insulin treatment
- > 3 daily oral antidiabetic drugs
- > 1 lipid lowering drug
- HbA1c > 65
Show all 21Show fewer
- 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
- Unable to give informed consent
- Allergy towards melatonin
- Daily consumption of benzodiazepines, fluvoxamine, amiodarone, efavirenz, fluoroquinolones, rifampicin, and carbamazepine due to interactions with the pharmacokinetics of melatonin.
- Severe sleep apnea (>30 respiration breaks/hour over 10 seconds)
- Medical treated depression or anxiety disorders within the last 3 years
- Daily consumption of selective serotonin reuptake inhibitors or tricyclic antidepressants
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the detailed description
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.
Main research questions:
- Does chronic melatonin treatment change insulin secretion in T2DM patients?
- Does chronic melatonin treatment change insulin sensitivity in T2DM patients?
- Does the MTNR1B rs10830963 risk allele alter the insulin secretion and insulin sensitivity compared with carries of the normal variant after chronic melatonin treatment?
- Does chronic melatonin treatment change insulin signalling in muscle - and adipose tissue? Design: A randomized, double-blinded, placebo controlled, crossover study, including 18 participants with T2DM. We aim to recruit 9 homozygous carriers of the normal allele and 9 hetero - or homozygous for the risk allele.
Participants will be examined on two occasions, 1) after 3 months of daily melatonin treatment before bedtime (10 mg), and 2) after 3 months of daily placebo treatment before bedtime.
On the study days, participants will initially undergo a basal period with glucose - and palmitate tracer infusions to assess endogenous glucose production and free fatty acid production. Afterwards a Botnia clamp, which combines an intravenous glucose tolerance test and a hyperinsulinemic euglycemic clamp, will be performed to assess β-cell function and insulin sensitivity. On both study days muscle - and fat biopsies will be performed under both basal and hyperinsulinemic euglycemic conditions.
Perspectives: It is highly relevant to evaluate the chronic effects of melatonin on glucose - and fat metabolism given the increase in melatonin consumption. Furthermore, the study may open for new treatment options of T2DM if beneficial effects of oral melatonin are detected.
- Conditions
- Metabolic Disease, Insulin Sensitivity, Glucose Metabolism Disorders (Including Diabetes Mellitus), Type 2 Diabetes Mellitus, Blood Pressure, Inflammation
- Being tested
- Melatonin, Placebo Oral Tablet
- Medical subject headings
- Metabolic Diseases, Insulin Resistance, Glucose Metabolism Disorders, Diabetes Mellitus, Type 2, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MelatoninDrug
Also called Melatonin treatment
Melatonin treatment
Placebo Oral TabletDrug
Also called Placebo treatment
Placebo treatment
| Study group | Role | What they receive |
|---|---|---|
| Melatonin | Active comparator | 10 mg melatonin each day 1 hour before bedtime for 3 months Receives: Drug: Melatonin |
| Placebo | Placebo comparator | Placebo each day 1 hour before bedtime for 3 months Receives: Drug: Placebo Oral Tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 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)
Measured: 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)
Measured: 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
Measured: 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
Ambulatory blood pressure assessed with Mobil-O-graph, I.E.M., Stolberg, Germany (Unit: mmHg)
Measured: The outcome will be measured after 3 months of placebo treatment and after 3 months of melatonin treatment
Change of arterial stiffness
Arterial stiffness assessed with Mobil-O-graph, I.E.M., Stolberg, Germany (unit: m/s)
Measured: The outcome will be measured after 3 months of placebo treatment and after 3 months of melatonin treatment
Change of gut microbiome
Feces analysis of microbial mRNA
Measured: The outcome will be measured after 3 months of placebo treatment and after 3 months of melatonin treatment
Change of sleep evaluation 1
Pittsburg Sleep Quality Index Questionnaire (Points on a scale: range 0-57)
Measured: The outcome will be measured after 3 months of placebo treatment and after 3 months of melatonin treatment
Change of sleep evaluation 2
Epworth Sleepiness Scale Questionnaire (Points on a scale: range 0-24)
Measured: After 3 months treatmentThe outcome will be measured after 3 months of placebo treatment and after 3 months of melatonin treatment
Change of psychological health 1
Major Depression Inventory Questionnaires (points on a scale: range 0-65)
Measured: The outcome will be measured after 3 months of placebo treatment and after 3 months of melatonin treatment
Change of psychological health 2
World Health Organization 5 Questionnaires (points on a scale: range 0-25)
Measured: The outcome will be measured after 3 months of placebo treatment and after 3 months of melatonin treatment
Hormonal changes
Ghrelin, HbA1c, GLP-1, GLP-2, GIP, free fatty acids (FFA), leptin, cytokines, adiponectin, growth hormone, cortisol, hsCRP, CD163, MBL, IGF-1 and proinsulin measured by ELISA, RIA, or routine biochemical analysis. Unit: pmol/L
Measured: The outcome will be measured after 3 months of placebo treatment and after 3 months of melatonin treatment
Change of glucose and palmitate kinetics
Tracer technique with infusion of radioactive labeled glucose and palmitate for determination of rate of appereance. Unit: mikromol/min
Measured: The outcome will be measured after 3 months of placebo treatment and after 3 months of melatonin treatment
Change of regional glucose and palmitate uptake
Forearm model with arteriovenous differences of glucose and palmitate (Arterial glucose minus venous glucose = forearm uptake (unit mmol/l). The same applies for palmitate
Measured: The outcome will be measured after 3 months of placebo treatment and after 3 months of melatonin treatment
Change of DEXA-scans
Evaluation of body composition and bone mineral density by DEXA-scan
Measured: The outcome will be measured after 3 months of placebo treatment and after 3 months of melatonin treatment
Change of assessment of respiratory quotient (RQ)
Assessment of respiratory quotient (RQ) with indirect calorimetry (unit: VCO2/VO2)
Measured: The outcome will be measured after 3 months of placebo treatment and after 3 months of melatonin treatment
Change of assessment of resting energy expenditure (REE)
Assessment of resting energy expenditure (REE) with indirect calorimetry (Unit J/s)
Measured: The outcome will be measured after 3 months of placebo treatment and after 3 months of melatonin treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Mar 2019
- Study start26 Sep 2019
- Primary completion3 May 2021
- Study completion18 Aug 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metabolic DiseaseStudies of the same condition, open and under way.
- More trials run by University of AarhusThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Randomized, placebo controlled, double blinded crossover study
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Aarhus
- Sponsor type
- University, hospital or other
- Collaborators
- University of Copenhagen
- Responsible party
- Sponsor
- Investigators
- Esben Stistrup Lauritzen, MD, Principal investigator, Medical Research LaboratoryUlla Kampmann Opstrup, MD, PhD, Principal investigator, Aarhus University HospitalJulie Støy, MD, PhD, Principal investigator, Aarhus University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03859934
- Sponsor's protocol ID
- 2019-000213-37
- Other IDs
- 2019
- Status last verified
- Aug 2021
- First submitted
- 18 Feb 2019
- Last updated
- 25 Aug 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Metabolic Effects of Melatonin Treatment
- ClinicalTrials.gov ID
- NCT03859934
- Acronym / sponsor ID
- 2019-000213-37
- Conditions
- Metabolic Disease, Insulin Sensitivity, Glucose Metabolism Disorders (Including Diabetes Mellitus), Type 2 Diabetes Mellitus, Blood Pressure, Inflammation
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 17 participants (actual)
- Lead sponsor
- University of AarhusUniversity, hospital or other
- Collaborators
- University of Copenhagen
- Study start
- 26 Sep 2019 (actual)
- Primary completion
- 3 May 2021 (actual)
- Study completion
- 18 Aug 2021 (actual)
- First posted
- 1 Mar 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Main research questions:
- Does chronic melatonin treatment change insulin secretion in T2DM patients?
- Does chronic melatonin treatment change insulin sensitivity in T2DM patients?
- Does the MTNR1B rs10830963 risk allele alter the insulin secretion and insulin sensitivity compared with carries of the normal variant after chronic melatonin treatment?
- Does chronic melatonin treatment change insulin signalling in muscle - and adipose tissue? Design: A randomized, double-blinded, placebo controlled, crossover study, including 18 participants with T2DM. We aim to recruit 9 homozygous carriers of the normal allele and 9 hetero - or homozygous for the risk allele.
Participants will be examined on two occasions, 1) after 3 months of daily melatonin treatment before bedtime (10 mg), and 2) after 3 months of daily placebo treatment before bedtime.
On the study days, participants will initially undergo a basal period with glucose - and palmitate tracer infusions to assess endogenous glucose production and free fatty acid production. Afterwards a Botnia clamp, which combines an intravenous glucose tolerance test and a hyperinsulinemic euglycemic clamp, will be performed to assess β-cell function and insulin sensitivity. On both study days muscle - and fat biopsies will be performed under both basal and hyperinsulinemic euglycemic conditions.
Perspectives: It is highly relevant to evaluate the chronic effects of melatonin on glucose - and fat metabolism given the increase in melatonin consumption. Furthermore, the study may open for new treatment options of T2DM if beneficial effects of oral melatonin are detected.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
- Model description
- Randomized, placebo controlled, double blinded crossover study
| Arm | Type | Receives |
|---|---|---|
| Melatonin | Active comparator | Drug: Melatonin10 mg melatonin each day 1 hour before bedtime for 3 months |
| Placebo | Placebo comparator | Drug: Placebo Oral TabletPlacebo each day 1 hour before bedtime for 3 months |
Who may qualify
- Ages
- 40 to 70 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Male sex
- Caucasian race
- Type 2 Diabetes Mellitus (T2DM)
- T2DM duration of maximum 20 years
- Age 40-70 years
Key exclusion criteria (21 listed)
- > 3 daily antihypertensive drugs
- Blood pressure > 160/100 mmHg
- Insulin treatment
- > 3 daily oral antidiabetic drugs
- > 1 lipid lowering drug
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MelatoninAlso: Melatonin treatmentMelatonin treatment | Drug | Melatonin |
| Placebo Oral TabletAlso: Placebo treatmentPlacebo treatment | Drug | Placebo |
Primary outcome
Change of insulin sensitivity
Time frame: 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
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)
Change of insulin secretion change
Time frame: The outcome will be measured after 3 months of placebo treatment and after 3 months of melatonin treatment
Insulin secretion is assessed by an intravenous glucose tolerance test, unit: pmol/L (insulin)
MTNR1a rs10830963 influence on change in insulin sensitivity and insulin secretion
Time frame: The outcome will be measured after 3 months of placebo treatment and again after 3 months of melatonin treatment
MTNR1a rs10830963 genotype influence on insulin sensitivity and insulin secretion (see outcome 1 + 2)
Change of insulin signalling
Time frame: The outcome will be measured after 3 months of placebo treatment and after 3 months of melatonin treatment
Insulin signalling in muscle and adipose tissue assessed by western blot
13 secondary outcomes
Change of ambulatory blood pressure
Time frame: The outcome will be measured after 3 months of placebo treatment and after 3 months of melatonin treatment
Change of arterial stiffness
Time frame: The outcome will be measured after 3 months of placebo treatment and after 3 months of melatonin treatment
Change of gut microbiome
Time frame: The outcome will be measured after 3 months of placebo treatment and after 3 months of melatonin treatment
Change of sleep evaluation 1
Time frame: The outcome will be measured after 3 months of placebo treatment and after 3 months of melatonin treatment
Change of sleep evaluation 2
Time frame: After 3 months treatmentThe outcome will be measured after 3 months of placebo treatment and after 3 months of melatonin treatment
Change of psychological health 1
Time frame: The outcome will be measured after 3 months of placebo treatment and after 3 months of melatonin treatment
Change of psychological health 2
Time frame: The outcome will be measured after 3 months of placebo treatment and after 3 months of melatonin treatment
Hormonal changes
Time frame: The outcome will be measured after 3 months of placebo treatment and after 3 months of melatonin treatment
Change of glucose and palmitate kinetics
Time frame: The outcome will be measured after 3 months of placebo treatment and after 3 months of melatonin treatment
Change of regional glucose and palmitate uptake
Time frame: The outcome will be measured after 3 months of placebo treatment and after 3 months of melatonin treatment
Change of DEXA-scans
Time frame: The outcome will be measured after 3 months of placebo treatment and after 3 months of melatonin treatment
Change of assessment of respiratory quotient (RQ)
Time frame: The outcome will be measured after 3 months of placebo treatment and after 3 months of melatonin treatment
Change of assessment of resting energy expenditure (REE)
Time frame: The outcome will be measured after 3 months of placebo treatment and after 3 months of melatonin treatment
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Aug 2021.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Esben Stistrup Lauritzen, MD principal investigator
Medical Research Laboratory
Ulla Kampmann Opstrup, MD, PhD principal investigator
Aarhus University Hospital
Julie Støy, MD, PhD principal investigator
Aarhus University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Melatonin in people with Metabolic Disease and Insulin Sensitivity, run by University of Aarhus at 1 site in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change of insulin sensitivity (time frame: 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). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Aug 2021.