Study to Investigate the Effects of Melatonin, Temazepam & Zolpidem on Sleep EEG in Men and Women
Condition: Insomnia
Study type: Interventional
Phase: Phase 1

Summary: 
      This study has been designed to compare the effects of melatonin with those of drugs
      (temazepam and zolpidem) regularly prescribed for the treatment of insomnia, in healthy,
      middle-aged volunteers.

      The study will take place at one centre. Volunteers consenting to participate in the study
      will have their eligibility confirmed by a screening panel, including spending one night in
      the sleep clinic to acclimatize to the study procedures. Blood and urine samples will be
      collected during this overnight visit.

      Volunteers continuing to remain eligible will receive, in turn, melatonin, temazepam,
      zolpidem and placebo as a single dose during 4 treatment phases lasting one night and
      separated by at least five days. Neither the volunteer nor the study staff will be aware of
      which drug each volunteer is receiving at each treatment phase.

      The volunteer's electrical brain activity will be measured whilst sleeping. Other aspects of
      sleep, including measures of sleep quality, will also be measured. Urine samples will be
      collected during each treatment phase.

      Volunteers will undergo an assessment of health prior to departure from the clinic at their
      last treatment phase, and study staff will telephone 2 weeks later to obtain further
      information on their health status.

      The primary study objective is to compare EEG power spectra during nonREM sleep in the
      slow-wave frequencies following administration with melatonin to temazepam.
    

Detailed description: 
      This four-way cross-over study has been designed to compare the effects of three drugs used
      in the treatment of insomnia on the brain electrical activity of healthy middle-aged
      volunteers during sleep. During each of four treatment phases, volunteers will receive either
      prolonged-release melatonin, temazepam, zolpidem or placebo, in sequence as governed by a
      pre-determined randomisation schedule.

      The study will be conducted at a single centre clinical research facility (Surrey CRC).

      Volunteers who are eligible following screening will be invited to return to the sleep clinic
      so that they may undergo a one-night period of acclimatisation to the study procedures (the
      polysomnography [PSG] screen, Visit 2). Following confirmation that the participant has
      adhered to the protocols restrictions, including tests for drugs of abuse and alcohol use,
      vital signs will be measured and the actigraph will be replaced. Twice before going to sleep
      and once on awakening, participants will complete a Karolinska Sleepiness Scale and undergo a
      Karolinska Drowsiness Test. Participants will then undergo polysomnography, a series of
      recordings of brain activity using electroencephalography and patterns of breathing, for an
      eight hour period of sleep. In the evening a cannula will be fitted so that repeat blood
      samples can be taken and this will be removed the next morning. During the course of the
      evening three urine samples and four blood samples will be taken for the purpose of assay for
      melatonin. Three additional blood samples will be taken during the night and urine will be
      collected. On awakening, urine will be collected and the participant's stability will be
      assessed using the Romberg test and the Heel-to-Toe Gait test.

      Following the PSG screen, volunteers will then undergo four periods of study (Visits 3
      through 6), each of one night and separated by at least five days, during which time
      participants will be administered either a single dose of prolonged-release melatonin or a
      matching placebo, and a single dose of temazepam, zolpidem or a matching placebo. During each
      of these periods, the same assessments as those conducted during the PSG screen will be
      repeated except that blood samples will not be drawn for melatonin assay.

      Prior to departure from the sleep centre on each participant's last treatment period (or at
      withdrawal if earlier), a physical examination including measurement of vital signs will be
      performed, 12-lead ECG recorded and the clinical safety laboratory evaluations repeated.

      Adverse events and concomitant medications will be recorded throughout the study from the
      time of screening to discontinuation.

      Two weeks after the final treatment period, participants will be contacted by telephone to
      confirm whether they have experienced any adverse events since completion of the study.

      A person's melatonin profile is widely recognised as a reliable marker of that individual's
      timing of the circadian clock. Study participants' plasma melatonin profiles will be measured
      during the PSG visit. Urinary melatonin will be measured during the PSG visit and all
      treatment periods.
    

Intervention name(s): Prolonged-release melatonin; Temazepam; Zolpidem; Placebo to match melatonin, zolpidem and temazepam
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): 2 mg tablet, once.; 20 mg capsule, once; 10 mg capsule, once; Placebo to match melatonin: tablet, once. Placebo to match zolpidem: capsule, once. Placebo to match temazepam: capsule, once.
Intervention MeSH terms: Melatonin; Zolpidem; Temazepam
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment