Metabolic Effects of Melatonin Treatment
Condition: Metabolic Disease; Insulin Sensitivity; Glucose Metabolism Disorders (Including Diabetes Mellitus); Type 2 Diabetes Mellitus; Blood Pressure; Inflammation
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2; Insulin Resistance; Metabolic Diseases; Glucose Metabolism Disorders; Inflammation
Study type: Interventional
Phase: Phase 1

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.
    

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:

        1. Does chronic melatonin treatment change insulin secretion in T2DM patients?

        2. Does chronic melatonin treatment change insulin sensitivity in T2DM patients?

        3. Does the MTNR1B rs10830963 risk allele alter the insulin secretion and insulin
           sensitivity compared with carries of the normal variant after chronic melatonin
           treatment?

        4. 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.
    

Intervention name(s): Melatonin; Placebo Oral Tablet
Intervention type(s): Drug; Drug
Intervention description(s): Melatonin treatment; Placebo treatment
Other intervention name(s): Melatonin treatment; Placebo treatment
Intervention MeSH terms: Melatonin
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: Randomized, placebo controlled, double blinded crossover study
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment