Sleep Deprivation
Conditions
Keywords
Sleep hygiene, Sleep latency, Elderly sleep, Nursing Home sleep
Brief summary
Older people living in nursing homes do not sleep very well for many reasons. Sleep disorders such as sleep apnea (when someone briefly stops breathing during sleep), and night time urination, along with the problems caused by the nighttime environment of the nursing home, such as noise and disruptive care routines can all contribute. Poor sleep can lead to other health problems or make existing health problems worse. This study will evaluate how well a sleep hygiene intervention and a medication for sleep (ramelteon (Rozerem)) work to improve sleep in nursing home residents with poor sleep. Ramelteon is FDA approved and has been tested in older adults living in the community, but not in older adults living in nursing homes. We expect sleep to improve on the study drug along with the sleep hygiene intervention, in comparison to placebo along with the sleep hygiene intervention. Based on adverse events reported in previous samples of older subjects, we expect the study drug to cause few side effects.
Detailed description
This study evaluates how well Ramelteon works by measuring sleep at night and during the day. After consenting and final determination of eligibility, participants will complete a baseline phase to assess usual sleep, as well as daytime alertness and activity , thinking and memory, walking and balance (among those who walk and/or stand), and mood. Sleep at night and during the day will be objectively assessed with wrist actigraphs in all subjects. Approximately half will also receive polysomnography to assess nighttime sleep. Subjects who sleep more than 75% of the time they are in bed will not continue in the study. Subjects that do not have improved sleep with the sleep hygiene program will be randomized to one of two treatment groups - one will receive the active drug along with the sleep hygiene intervention and the other will receive a placebo along with the sleep hygiene intervention. Following randomization, subjects will complete a brief run-in phase and then enter the treatment phase. Assessment of sleep and other measures will be repeated. The primary hypotheses to be examined in this study are as follows: Hypothesis 1: Subjects treated with ramelteon in addition to a sleep hygiene (SHI) will have improved sleep latency, and as a consequence, a significant increase in actigraphically measured sleep efficiency, compared to subjects treated with placebo plus a SHI. Hypothesis 2: Subjects treated with ramelteon in addition to a SHI will sleep less and spend less time in bed during the day, be more engaged in daytime activities, and have better mood than subjects treated with placebo plus a SHI. Hypothesis 3: Changes in daytime sleep, time in bed during the day, engagement in activities, and mood will be positively correlated with improved sleep efficiency among subjects receiving ramelteon in addition to a SHI.
Interventions
DRUGRamelteon
Subjects demonstrating low sleep efficiencies and prolonged sleep latencies, will be randomly assigned to continue to receive SHI accompanied by either placebo or Ramelteon (8 mg). Matching placebo will be obtained and the medication pre-packaged and ordered based on the randomization results.
DRUGPlacebo
Sponsors
National Institutes of Health (NIH)
Emory University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
65 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* After initial screening and consenting, subjects with a 5-night average baseline sleep efficiency of less than or equal to 75% will be included
Exclusion criteria
* Less than 65 yrs old * Bedbound * Resided in NH for less than two months * Patients on Medicare Part A skilled Benefit(anticipated short length stay) - Terminal Illness * Unstable psychotropic drug regimen (addition, discontinuation, or change of dosage of any psychotropic drug in the prior two weeks) - Use of hypnotic, antihistamine, or benzodiazepine more than once per week during the two weeks before screening * Use of drugs that could potentially inhibit the metabolism of Ramelteon (ie: fluvoxamine, ketoconazole, fluconazole) * Use of Drugs that induce the metabolism of Ramelteon (ie: rifampin)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Meeting Good Sleep Latency Criteria | All assessment periods, up to one week | Sleep Latency Criteria for Good Latency measured by behavioral observations conducted every 10-15 minutes after 4pm until 11pm. Good latency is described as subject asleep in under 20 minutes on 51% of the nights observed in a week. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Sleep Efficiency | All Assessment Phases, up to one week | % of time asleep holding time in bed constant (averaged over 3-5 nights) |
| Daytime Engagement Status | All Assessment Phases, up to one week | Trained research technicians observed the subjects behavior during assessment phases every 15 minutes for one full minute. Specific behavioral definitions were employed to record whether the subject was in or out of bed, awake or asleep (eyes closed with no purposeful movement for at least 60 consecutive seconds), actively engaged in an activity (reading, watching television, conversation, a specific group activity, etc), and whether any physical or verbal agitation was noted. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Daytime Sleep | All Assessment Phases, up to one week | As measured by percent of daytime behavioral observations observed asleep |
Participant flow
Recruitment details
Subjects were long-stay residents of NHs in the Atlanta area who were \> age 65. Potential subjects were initially screened using administrative data and medical record review. Potential subjects who do not meet any of the exclusion criteria after initial screening were approached for informed consent or proxy consent was obtained when applicable.
Pre-assignment details
Those for whom consent was obtained underwent a clinical assessment and baseline measures . Only subjects with 5-night average sleep latency \> 20 minutes and/or sleep efficiency \<80% were included . Subjects with severe sleep apnea were excluded and referred to their primary physician. Subjects unable to tolerate the actiwatches were excluded.
Participants by arm
| Arm | Count |
|---|---|
| Ramelteon 6 Weeks of Sleep Hygiene Intervention (SHI) followed by Placebo Run-in (3 days) then Active Drug (Ramelteon) for those whose sleep did not improve. | 11 |
| Placebo 6 Weeks of Sleep Hygiene Intervention (SHI) followed by Placebo Run-in (3 days) then Placebo for those whose sleep did not improve with SHI alone. | 11 |
| Total | 22 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Baseline | Medication Change by PCP of subject | 1 |
| Baseline | Physician Decision | 9 |
| Baseline | Withdrawal by Subject | 3 |
| Clinical Assessment | Death | 1 |
| Clinical Assessment | Lack of Efficacy | 24 |
| Clinical Assessment | Physician Decision | 1 |
| Clinical Assessment | Withdrawal by Subject | 10 |
| Sleep Hygiene Behavioral Intervention | Death | 1 |
| Sleep Hygiene Behavioral Intervention | Medication Change by PCP for subject | 1 |
| Sleep Hygiene Behavioral Intervention | Responded to intervention | 4 |
| Sleep Hygiene Behavioral Intervention | Withdrawal by Subject | 1 |
| Sleep Hygiene With the Placebo | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Placebo | Ramelteon | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 11 Participants | 11 Participants | 22 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 85.0 years STANDARD_DEVIATION 8.9 | 83.9 years STANDARD_DEVIATION 6.8 | 85.0 years STANDARD_DEVIATION 7.5 |
| Region of Enrollment United States | 11 participants | 11 participants | 22 participants |
| Sex: Female, Male Female | 8 Participants | 8 Participants | 16 Participants |
| Sex: Female, Male Male | 3 Participants | 3 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 11 | 0 / 11 |
| serious Total, serious adverse events | 0 / 11 | 0 / 11 |
Outcome results
Primary
Number of Participants Meeting Good Sleep Latency Criteria
Sleep Latency Criteria for Good Latency measured by behavioral observations conducted every 10-15 minutes after 4pm until 11pm. Good latency is described as subject asleep in under 20 minutes on 51% of the nights observed in a week.
Time frame: All assessment periods, up to one week
Population: 30 subjects enrolled into the behavioral intervention. 4 subjects responded to the sleep hygiene intervention (SHI) arm and completed the study. 3 subjects were excluded for various reasons from the SHI arm. 23 subjects continued onto the placebo/SHI. 1 subject withdrew from that arm. From there,11 subjects received drug and 11 remained on placebo
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ramelteon | Number of Participants Meeting Good Sleep Latency Criteria | 7 participants |
| Placebo | Number of Participants Meeting Good Sleep Latency Criteria | 6 participants |
p-value: 0.65595% CI: [0.156, 8.717]Chi-squared
Secondary
Daytime Engagement Status
Trained research technicians observed the subjects behavior during assessment phases every 15 minutes for one full minute. Specific behavioral definitions were employed to record whether the subject was in or out of bed, awake or asleep (eyes closed with no purposeful movement for at least 60 consecutive seconds), actively engaged in an activity (reading, watching television, conversation, a specific group activity, etc), and whether any physical or verbal agitation was noted.
Time frame: All Assessment Phases, up to one week
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ramelteon | Daytime Engagement Status | 54.6 percentage of engaged observations | Standard Deviation 24.6 |
| Placebo | Daytime Engagement Status | 54.6 percentage of engaged observations | Standard Deviation 24.6 |
Secondary
Sleep Efficiency
% of time asleep holding time in bed constant (averaged over 3-5 nights)
Time frame: All Assessment Phases, up to one week
Population: Per protocol -- intention to treat - ITT - last carried forward.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ramelteon | Sleep Efficiency | 76.5 percentage of sleep | Standard Deviation 11.8 |
| Placebo | Sleep Efficiency | 73.8 percentage of sleep | Standard Deviation 14.9 |
Other Pre-specified
Daytime Sleep
As measured by percent of daytime behavioral observations observed asleep
Time frame: All Assessment Phases, up to one week
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ramelteon | Daytime Sleep | 19.4 percentage of daytime sleep observations | Standard Deviation 23.1 |
| Placebo | Daytime Sleep | 21.7 percentage of daytime sleep observations | Standard Deviation 29 |