Glucose Metabolism DisordersPhase 1/2NCT03204877
Acute Metabolic Effects of Melatonin Treatment
A Phase 1/2 study testing Melatonin in people with Glucose Metabolism Disorders, 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 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. Read more about this study
- Who is it for?
- Ages 20 to 40 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Glucose Metabolism Disorders
- What is being tested?
- Melatonin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 36 participants
- Where
- 1 siteDenmark
- Study dates
- 22 Aug 2017to 1 Feb 2020
- Phase
- Phase 1/2
- 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 20 to 40 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Male sex
- Age 20-40 years
- BMI between 22-30 kg/m2
- Written consent prior to study participation
Who cannot join
- 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
Show all 12Show fewer
- 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
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 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.
Read the 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
- Conditions
- Glucose Metabolism Disorders
- Being tested
- Melatonin, Placebo
- Keywords
- Melatonin, Insulin sensitivity, Insulin secretion, Incretin response
- Medical subject headings
- Glucose Metabolism Disorders, Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MelatoninDrug
Oral capsules
PlaceboOther
Oral capsules
| Study group | Role | What they receive |
|---|---|---|
| Melatonin | Active comparator | Four capsules of Melatonin 10 mg is administered orally every hours for four hours during the study day. Receives: Drug: Melatonin |
| Placebo | Placebo comparator | Four capsules of placebo is administered orally every hours for four hours during the study day. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Insulin sensitivity
Insulin sensitivity is assessed by a hyperinsulinemic euglycemic clamp, unit: mg/kg/min
Measured: 2 hours (from t= 105 to 225 minutes)
Insulin secretion
Insulin secretion is assessed by an intravenous glucose tolerance test, unit: pmol/L (insulin)
Measured: 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)
Measured: 4 hours (from t = 0 to 240 minutes)
Secondary outcomes (3)
Inflammatory markers
Assessed by blood samples, unit: pg/mL
Measured: Baseline t = -60 minutes and at t = 45 minutes
Substrate oxidation
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
Measured: From t=15 minutes to 45 minutes and from t=195 minutes to 225 minutes
Hormones
Hormones are assessed by blood samples. Units: C-peptide: pmol/L; Cortisol: ng/mL; Adiponectin: mg/L; IGF-I (ng/ml)
Measured: Baseline t = -60 minutes and at t = 45 minutes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jul 2017
- Study start22 Aug 2017
- Primary completion27 Feb 2019
- Study completion1 Feb 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Glucose Metabolism DisordersStudies 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 1/2
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 36 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Aarhus
- Sponsor type
- University, hospital or other
- Collaborators
- University of Copenhagen
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03204877
- Sponsor's protocol ID
- Mel06062017
- Status last verified
- Mar 2020
- First submitted
- 6 Jun 2017
- Last updated
- 25 Mar 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 37844838Lauritzen 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.
PubMed 34265066Kampmann 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.
PubMed 33220095
Study at a glance
From the registry record, last updated by the sponsor on 25 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Acute Metabolic Effects of Melatonin Treatment
- ClinicalTrials.gov ID
- NCT03204877
- Acronym / sponsor ID
- Mel06062017
- Conditions
- Glucose Metabolism Disorders
- Keywords
- Melatonin, Insulin sensitivity, Insulin secretion, Incretin response
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 36 participants (actual)
- Lead sponsor
- University of AarhusUniversity, hospital or other
- Collaborators
- University of Copenhagen
- Study start
- 22 Aug 2017 (actual)
- Primary completion
- 27 Feb 2019 (actual)
- Study completion
- 1 Feb 2020 (actual)
- First posted
- 2 Jul 2017 (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 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.
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 design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Melatonin | Active comparator | Drug: MelatoninFour capsules of Melatonin 10 mg is administered orally every hours for four hours during the study day. |
| Placebo | Placebo comparator | Other: PlaceboFour capsules of placebo is administered orally every hours for four hours during the study day. |
Who may qualify
- Ages
- 20 to 40 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Male sex
- Age 20-40 years
- BMI between 22-30 kg/m2
- Written consent prior to study participation
Key exclusion criteria (12 listed)
- 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
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 |
|---|---|---|
| MelatoninOral capsules | Drug | Melatonin |
| PlaceboOral capsules | Other | Placebo |
Primary outcome
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
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)
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)
3 secondary outcomes
Inflammatory markers
Time frame: 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
Hormones
Time frame: Baseline t = -60 minutes and at t = 45 minutes
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 Mar 2020.
- Derived from this study: PubMed 37844838Pedersen 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.
- Derived from this study: PubMed 34265066Lauritzen 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.
- Derived from this study: PubMed 33220095Kampmann 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.
- 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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Melatonin in people with Glucose Metabolism Disorders, 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 4 inclusion and 12 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 Mar 2020. 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Insulin sensitivity (time frame: 2 hours (from t= 105 to 225 minutes)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03204877, which also lists 3 linked publications.
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 Mar 2020.