Melatonin Receptor Agonist and Peripheral Biological Markers
Condition: Insomnia
Study type: Observational

Summary: 
      People who have insomnia typically co-occur with mental disorders, especially anxiety and
      depression. It has been documented that the melatonin phase in the depressed patients was
      reached with a delay. Melatonin plays a crucial role in regulation of circadian-clock-related
      gene expression.
    

Detailed description: 
      The higher values of circadian-clock-related proteins observed at day (brain and muscle aryl
      hydrocarbon receptor nuclear translocator-like protein 1 and circadian locomoter output
      cycles protein kaput1) and night (period circadian protein homolog 1 and cryptochrome).
      Melatonin receptor type 1 (MT1) and melatonin receptor type 2 (MT2) are present in mammals
      including humans and involved in sleep-wake cycle. RamelteonRMT (RMT, Rozerem®), a novel MT1
      and MT2 agonist, has been approved for treatment of insomnia, and provides a strong phase
      shift signal to the circadian timing system. Melatonin receptor agonists have recently become
      available for treatment of sleep and psychiatric disorders; however, the effects of the
      melatonin receptor agonist on peripheral biological markers of circadian rhythm are still to
      elucidate. This is a non-randomized, observational study, which aims of this study is to
      evaluate the effects of ramelteon RMT in melatonin level and the regulation of circadian
      rhythm genes expression in patients with primary insomnia, and/or major depressive disorder
      (MDD) on, or generalized anxiety disorder (GAD) with symptoms of insomnia. Forty
      Participants: Participants aged 20-80 years with body mass index between 18 and 34 and
      without any ambulatory problems will be recruited according to clinical judgment to take RMT
      for insomnia, ages 20-80 years, body mass index between 18 and 34, without any ambulatory
      problems, and be willing to write sleep diary. Primary insomnia, MDD and GAD will be as
      defined by the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition Revised for
      at least 3 months and a history of daytime complaint(s) associated with disturbed sleep.
      Participants were administered the ramelteon RMT tablet (8 mg/Tab) by oral intake at the same
      time, which is 2 hours prior to the schedule bedtime every night for eight weeks. The
      peripheral blood is collected at two time points - ramelteon RMT administration week 0 and
      week 8, and the melatonin, circadian-clock-related day genes (Aryl hydrocarbon receptor
      nuclear translocator-like protein 1 and Circadian locomoter output cycles protein kaput1) and
      night genes (circadian protein homolog 1 and cryptochrome) expression variation will be
      quantified and compared to determine circadian rhythm phase shift. The expected findings are
      the circadian-clock-related genes would shift to normal baseline and these genes expressions
      will be the peripheral marker for evaluation of drug treatment efficacy.
    

Intervention name(s): melatonin
Intervention type(s): Drug
Intervention description(s): Ramelteon RMT (RMT, Rozerem®), a novel MT1 and MT2 agonist, has been approved for treatment of insomnia, and provides a strong phase shift signal to the circadian timing system. Melatonin receptor agonists have recently become available for treatment of sleep and psychiatric disorders
Intervention MeSH terms: Melatonin
Observational model: Other
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        1. Out-patients with primary insomnia and patients with major depressive disorder (MDD)
             and generalized anxiety disorder (GAD) with chief complaint of insomnia or a history
             of daytime complaint(s) associated with disturbed sleep. The diagnosis of MDD and GAD
             will be made made according to the diagnostic criteria of the Diagnostic and
             Statistical Manual of Mental Disorders (DSM-IV-TR) Revised for at least 3 months.

          2. Patients are 20-80 years old, body mass index between 18 and 34, and without any
             ambulatory problems.
      
Biospecimen description: 
      The higher values of circadian-clock-related proteins observed at day (brain and muscle aryl
      hydrocarbon receptor nuclear translocator-like protein 1 and circadian locomoter output
      cycles protein kaput1) and night (period circadian protein homolog 1 and cryptochrome).
      Melatonin receptor type 1 (MT1) and melatonin receptor type 2 (MT2) are present in mammals
      including humans and involved in sleep-wake cycle.
    
Keywords: melatonin; melatonin receptor agonist; circadian-clock-related genes