Insomnia, Sleep Disorders, Spinal Cord Injury, Tetraplegia
Conditions
Keywords
sleep, melatonin, spinal cord injury, insomnia, tetraplegia
Brief summary
The purpose of this study is to determine if replacing melatonin function with a melatonin agonist (ramelteon) in individuals that lack endogenous melatonin production (tetraplegia) helps to alleviate self-reported sleep disruption.
Interventions
DRUGRamelteon
8 mg nightly
DRUGPlacebo
Nightly 8mg of placebo (same appearance as ramelteon)
Sponsors
Stanford University
Takeda
US Department of Veterans Affairs
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Age 18 years or older, male or female veterans of any racial or ethnic group * Neurologically complete (Frankel A or B) damage to the lower (C4-C8) cervical spinal cord * Absence of melatonin production * Time since SCI is greater than 6 months \[no cases of acute spinal cord injury\] * Subjective complaint of sleep disruption
Exclusion criteria
* Current use of fluvoxamine (Luvox , antidepressant), rifampin (antimycobacterial), ketoconazole (Nizoral , antifungal), or fluconazole (Diflucan , antifungal) \[these interact with the same liver enzyme that is the primary metabolizer of ramelteon\]; use of sleep medications is okay * Hepatic dysfunction * Concomitant use of over-the-counter melatonin * Pregnancy or breast feeding * Currently or have within the past six months met DSM-IV (Diagnosis and Statistical Manual IV) criteria for drug or alcohol abuse or dependence or AUDIT score \>19 * Acute illness or unstable chronic illness. Use of continuous positive airway pressure (CPAP) for treatment of sleep apnea is acceptable. * No travel across three or more time zones within three weeks or during the protocol * Illiterate or unable to read or write English or are judged by the investigator to be unable or unlikely to follow the study protocol
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Amount of Wakefulness After Sleep Onset (WASO) | 10 weeks | Measured as the median of the average WASO of the three weeks of either placebo or ramelteon treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Subjective Morning Alertness | 10 weeks | Measured as the median of the average morning alertness (measured from 1-7 on the Stanford Sleepiness Scale, a Likert-like scale in which higher values are lower alertness) of the three weeks of either placebo or ramelteon treatment |
Countries
United States
Participant flow
Recruitment details
Subjects recruited from community
Pre-assignment details
Subjects excluded if baseline measure detected the presence of melatonin metabolite in their urine.
Participants by arm
| Arm | Count |
|---|---|
| Arm 1 Ramelteon then placebo
Ramelteon : 8 mg nightly | 4 |
| Arm 2 Placebo then ramelteon
Placebo : Nightly 8mg of placebo (same appearance as ramelteon) | 4 |
| Total | 8 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Physician Decision | 0 | 1 |
| Overall Study | Protocol Violation | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Arm 2 | Arm 1 | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants | 4 Participants | 8 Participants |
| Age, Continuous | 55.5 years STANDARD_DEVIATION 15.5 | 51.25 years STANDARD_DEVIATION 9.74 | 53 years STANDARD_DEVIATION 12 |
| Region of Enrollment United States | 4 participants | 4 participants | 8 participants |
| Sex: Female, Male Female | 1 Participants | 0 Participants | 1 Participants |
| Sex: Female, Male Male | 3 Participants | 4 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 4 | 0 / 4 |
| serious Total, serious adverse events | 0 / 4 | 0 / 4 |
Outcome results
Primary
Amount of Wakefulness After Sleep Onset (WASO)
Measured as the median of the average WASO of the three weeks of either placebo or ramelteon treatment
Time frame: 10 weeks
Population: All participants who completed the entire protocol.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ramelteon | Amount of Wakefulness After Sleep Onset (WASO) | 72.3 Minutes |
| Placebo | Amount of Wakefulness After Sleep Onset (WASO) | 76.5 Minutes |
p-value: 0.7Friedman
Secondary
Change in Subjective Morning Alertness
Measured as the median of the average morning alertness (measured from 1-7 on the Stanford Sleepiness Scale, a Likert-like scale in which higher values are lower alertness) of the three weeks of either placebo or ramelteon treatment
Time frame: 10 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ramelteon | Change in Subjective Morning Alertness | 2.86 units on a scale |
| Placebo | Change in Subjective Morning Alertness | 3.14 units on a scale |
p-value: 0.35Friedman