InsomniaPhase 1NCT00940550
Study to Investigate the Effects of Melatonin, Temazepam & Zolpidem on Sleep EEG in Men and Women
A Phase 1 study testing Prolonged-release melatonin, Temazepam and Zolpidem in people with Insomnia, run by University of Surrey at 1 site in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 55 to 64 yearsHealthy volunteers can take part
- Conditions the study is for
- Insomnia
- What is being tested?
- Prolonged-release melatonin, Temazepam and Zolpidem
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 16 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Jul 2009to Aug 2009
- 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 55 to 64 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- The subject is able to read and understand the Informed Consent Form (ICF), and understand study procedures.
- The subject has signed the ICF.
- Healthy male or female subjects aged 55-64 years inclusive. Attempts will be made to achieve an equal gender ratio through appropriate screening procedures, but a failure to do so will not preclude analysis of the final data set.
- The subject has a history of the following sleep characteristics during the past three months or more at Visit 1:
- Bedtime between 22:00-00:00h on at least five nights per week
- Reported typical nightly sleep duration between 6.5 and 8.5 h
Show all 9Show fewer
- The subject has a regular sleep-wake cycle and maintains a regular sleep-wake cycle during the study
- The subject is a non-smoker who has not used nicotine or nicotine-containing products for at least approximately 6 months. Subjects who have discontinued smoking or the use of nicotine/nicotine containing products for at least approximately 3 months may be enrolled in the study at the discretion of the investigator.
- The subject is, in the opinion of the investigator, healthy on the basis of a physical examination, medical history, vital signs, ECG, and the results of routine laboratory tests.
Who cannot join
- The subject is female AND of childbearing potential. Female volunteers will be considered not of child-bearing potential if they are:
- Pre-menopausal women who have been surgically sterilized by bilateral oopherectomy and/or hysterectomy, OR
- Post-menopausal, defined as:
- No spontaneous menstruation for at least one year prior to the first dose,
- Follicular stimulation hormone (FSH) >18mIU/mL, AND
- Not lactating.
Show all 24Show fewer
- The subject has a known sensitivity to temazepam, zolpidem or melatonin or a history of any allergy that in the opinion of the investigator would contraindicate subject participation.
- The subject has a BMI of less than 19, or more than 33kg/m or a total body weight of less than 50 kilograms at pre-study (screening) visit. BMI is calculated by taking the subject's weight in kg and dividing by the subject's height in metres, squared.
- The subject has a score of >5 points on the Pittsburgh Sleep Quality Index (PSQI) scale.
- The subject has a history of clinically significant sleep pathology according to DSM-IV TRTM or presents symptoms of clinically significant sleep pathology at PSG screening. AHI of >10 and PLMAI of >10.
- The subject is a shift worker or maintains an irregular sleep-wake schedule during 1 month preceding the screening visit, or travelled within the last month preceding the screening visit and/or during the study to a time zone more than 2 hours different to the current time zone in Surrey.
- The subject consumes more than three (men) or two (women) units of alcohol per day on average over the 1 month preceding Visit 1(screening visit) [NOTE: 1 unit is equivalent to a half-pint (220mL) of beer or 1 (25mL) measure of spirits or 1 glass (125mL) of wine].
- The subject consumes more than 5 caffeine-containing beverages per day.
- Clinically significant psychiatric, cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, neurological (particularly myasthenia gravis), immunological, or haematological disease or abnormality, as determined by the study physician.
- History of alcohol, narcotic, benzodiazepine, or other substance abuse or dependence within the 12 months preceding Visit 1.
- Positive urine drug screen at any visit at Surrey CRC (i.e., amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, or opiates). A repeat test will not be allowed.
- Positive alcohol breath test at any visit to Surrey CRC. A repeat test will not be allowed. [NOTE: subjects must be told to avoid consumption of alcoholic beverages for at least 24 hours prior to attending the Centre].
- Use of any psychotropic medications such as benzodiazepines, barbiturates and narcotics, or other medications, including over the counter (OTC) and herbal products including melatonin that may affect sleep/wake function, within the 3 months or 5 half-lives preceding Visit 1, whichever is longer, or a need to use any of these medications during the study.
- Use of any other medication which may interfere with study outcome and/or interfere with IMP within the 2 weeks or 5 half lives preceding Visit 2, with the exception of non-steroidal analgesics, and paracetamol. [NOTE: Concomitant medications which do not influence study outcome and/or do not interfere with IMP may be allowed at the discretion of the investigator].
- Hereditary problems of galactose intolerance, the Lapp lactase deficiency, or glucose-galactose malabsorption.
- Currently participating in another clinical trial with an investigational or non-investigational drug or device, or has participated in another clinical trial within the 3 months preceding Visit 1 (screening visit).
- Concomitant use of HRT by female volunteer.
- Any condition that, in the investigator's opinion, compromises the volunteer's ability to meet protocol requirements or to complete the study.
- Subject must be able to refrain from strenuous or unaccustomed exercise such as weight lifting, running and bicycling 24 hours before visits 2, 3, 4, 5 and 6, and 24 hours after visits 2, 3, 4, 5, and 6.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Surrey CRC, University of Surrey, Egerton Road
Guildford, Surrey, GU2 7XP
About this study
Official title: A Randomised, Double-Blind, Placebo-Controlled Four-Way Cross-Over Trial to Study the Effects of Prolonged-Release Melatonin, Temazepam and Zolpidem on the Spectral Composition of the EEG During Nocturnal Sleep in Healthy Middle-Aged Men and Women
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.
Read more
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.
Read the 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.
- Conditions
- Insomnia
- Being tested
- Prolonged-release melatonin, Temazepam, Zolpidem, Placebo to match melatonin, zolpidem and temazepam
- Medical subject headings
- Sleep Initiation and Maintenance Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Prolonged-release melatoninDrug
2 mg tablet, once.
TemazepamDrug
20 mg capsule, once
ZolpidemDrug
10 mg capsule, once
Placebo to match melatonin, zolpidem and temazepamDrug
Placebo to match melatonin: tablet, once. Placebo to match zolpidem: capsule, once. Placebo to match temazepam: capsule, once.
| Study group | Role | What they receive |
|---|---|---|
| Prolonged-release melatonin 2 mg | Experimental | Not described Receives: Drug: Prolonged-release melatonin |
| Temazepam 20 mg | Active comparator | Not described Receives: Drug: Temazepam |
| Zolpidem 10 mg | Active comparator | Not described Receives: Drug: Zolpidem |
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo to match melatonin, zolpidem and temazepam |
What is being measured
The primary outcome is the main question the study is designed to answer.
EEG Power density in slow wave frequencies during NREM sleep
Measured: Treatment Periods 1 to 4
Secondary outcomes (1)
EEG power density 0.25-32.0 Hz in NREM and REM sleep. EEG power density in the theta frequencies during the Karolinska Drowsiness Test. Objective polysomnography measures of sleep
Measured: Treatment Periods 1 to 4
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jul 2009 (estimated)
- Study startJul 2009
- Primary completionAug 2009
- Study completionAug 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for InsomniaStudies of the same condition, open and under way.
- 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
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Surrey
- Sponsor type
- University, hospital or other
- Collaborators
- H. Lundbeck A/S
- Investigators
- Dr. Daryl Bendel, MBChB, Study director, Surrey CRCDr. Malgorzata Knurowska, MD, Principal investigator, Surrey CRCProfessor Derk-Jan Dijk, Ph.D., B.S., M.S, Study chair, Surrey Sleep Research Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00940550
- Sponsor's protocol ID
- CRC 266
- Status last verified
- Nov 2009
- First submitted
- 15 Jul 2009
- Last updated
- 8 Aug 2011
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Aug 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomised, Double-Blind, Placebo-Controlled Four-Way Cross-Over Trial to Study the Effects of Prolonged-Release Melatonin, Temazepam and Zolpidem on the Spectral Composition of the EEG During Nocturnal Sleep in Healthy Middle-Aged Men and Women
- ClinicalTrials.gov ID
- NCT00940550
- Acronym / sponsor ID
- CRC 266
- Conditions
- Insomnia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- University of SurreyUniversity, hospital or other
- Collaborators
- H. Lundbeck A/S
- Study start
- Jul 2009
- Primary completion
- Aug 2009 (actual)
- Study completion
- Aug 2009 (actual)
- First posted
- 16 Jul 2009 (estimated)
- 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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Prolonged-release melatonin 2 mg | Experimental | Drug: Prolonged-release melatonin |
| Temazepam 20 mg | Active comparator | Drug: Temazepam |
| Zolpidem 10 mg | Active comparator | Drug: Zolpidem |
| Placebo | Placebo comparator | Drug: Placebo to match melatonin, zolpidem and temazepam |
Who may qualify
- Ages
- 55 to 64 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- The subject is able to read and understand the Informed Consent Form (ICF), and understand study procedures.
- The subject has signed the ICF.
- Healthy male or female subjects aged 55-64 years inclusive. Attempts will be made to achieve an equal gender ratio through appropriate screening procedures, but a failure to do so will not preclude analysis of the final data set.
- The subject has a history of the following sleep characteristics during the past three months or more at Visit 1:
- The subject is a non-smoker who has not used nicotine or nicotine-containing products for at least approximately 6 months. Subjects who have discontinued smoking or the use of nicotine/nicotine containing products for at least approximately 3 months may be enrolled in the study at the discretion of the investigator.
Key exclusion criteria (24 listed)
- The subject is female AND of childbearing potential. Female volunteers will be considered not of child-bearing potential if they are:
- The subject has a known sensitivity to temazepam, zolpidem or melatonin or a history of any allergy that in the opinion of the investigator would contraindicate subject participation.
- The subject has a BMI of less than 19, or more than 33kg/m or a total body weight of less than 50 kilograms at pre-study (screening) visit. BMI is calculated by taking the subject's weight in kg and dividing by the subject's height in metres, squared.
- The subject has a score of >5 points on the Pittsburgh Sleep Quality Index (PSQI) scale.
- The subject has a history of clinically significant sleep pathology according to DSM-IV TRTM or presents symptoms of clinically significant sleep pathology at PSG screening. AHI of >10 and PLMAI of >10.
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 |
|---|---|---|
| Prolonged-release melatonin2 mg tablet, once. | Drug | Prolonged-release melatonin 2 mg |
| Temazepam20 mg capsule, once | Drug | Temazepam 20 mg |
| Zolpidem10 mg capsule, once | Drug | Zolpidem 10 mg |
| Placebo to match melatonin, zolpidem and temazepamPlacebo to match melatonin: tablet, once. Placebo to match zolpidem: capsule, once. Placebo to match temazepam: capsule, once. | Drug | Placebo |
Primary outcome
EEG Power density in slow wave frequencies during NREM sleep
Time frame: Treatment Periods 1 to 4
1 secondary outcome
EEG power density 0.25-32.0 Hz in NREM and REM sleep. EEG power density in the theta frequencies during the Karolinska Drowsiness Test. Objective polysomnography measures of sleep
Time frame: Treatment Periods 1 to 4
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 8 Aug 2011.
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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.
Dr. Daryl Bendel, MBChB study director
Surrey CRC
Dr. Malgorzata Knurowska, MD principal investigator
Surrey CRC
Professor Derk-Jan Dijk, Ph.D., B.S., M.S study chair
Surrey Sleep Research Centre
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 Prolonged-release melatonin, Temazepam and Zolpidem in people with Insomnia, run by University of Surrey at 1 site in United Kingdom.
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 9 inclusion and 24 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 8 Aug 2011. 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 United Kingdom. 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?
EEG Power density in slow wave frequencies during NREM sleep (time frame: Treatment Periods 1 to 4). 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 8 Aug 2011.