Insomnia
Conditions
Keywords
Insomnia
Brief summary
The purpose of this study is to help scientist better understand the effect of a 12-week single daily evening dose of ramelteon (Rozerem ©), a drug that has been approved by the U. S. Food and Drug Administration (FDA) for the treatment of insomnia (trouble falling asleep or staying asleep). The study will measure levels of inflammation, fasting insulin and fasting glucose (sugar) in subjects who are taking either ramelteon (8 mg) or placebo.
Interventions
DRUGramelteon
DRUGplacebo
Sponsors
Duke University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
At screening visit: * aged 18-65 * nonsmokers * for women: oral contraceptive (OC) or hormone replacement therapy (HRT) nonusers To schedule the baseline PSG (Visit 2), subjects must meet the following inclusion criteria: * ages 18-65 inclusive; * PSQI-Component 2 (sleep latency) score of greater than 1; * non-smoker (e.g., less than 20 cigarettes in the past 5 years); * habitual bedtime between 8:30 pm and midnight * For premenopausal women: * regular menstrual cycles determined by Framingham Study criteria; * not pregnant and no history of oral contraceptive (OC) usage in last 6-months. * For postmenopausal women: * no recent (\< 6 months) use of Hormone Replacement Therapy (HRT) * no surgical menopause
Exclusion criteria
* positive urine drug screen * Potential subjects with hypersensitivity to ramelteon or any components of the formulation will be excluded from participation. * Given that ramelteon should not be used by individuals with severe hepatic impairment, or in patients in combination with fluvoxamine, individuals who report liver problem or use of fluvox will be excluded. * use of rifampin (Rifadin ©); ketoconazole (Nizora ©l); or fluconazole (Diflucan ©). * Ramelteon has not been studied in children or adolescents, and the effects in these populations are unknown, thus only individuals above 18 years will participate.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Sleep Onset Latency (SOL) as Measured by Pittsburgh Sleep Qualtiy Index (PSQI) | baseline | Subjects completed component 2 of the PSQI questionnaire. Component 2 asks questions about sleep latency and is scored on a scale from 0 (better) to 3 (worse). |
| Sleep Onset Latency (SOL) as Measured by Self Report (Sleep Diary) | Day 89-90 | The average of a week of sleep onset latency data from the sleep diary filled out in the morning by the participating subjects. Sleep latency is defined as the length of time it takes from lying down for the night until sleep onset. |
| Mean Latency to Persistent Sleep (LPS) Via Polysomnography | Day 89-90 | Elapsed time from the beginning of the Polysomnography recording to the onset of the first 20 minutes of continuous sleep was measured. |
| Change in Metabolic Syndrome (MetSyn) | Baseline, Day 30, Day 60, Day 89-90 | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Total Sleep Time | Day -1-0, Day 89-90 | Change in sleep time will be determined by PSG. |
| Inflammatory Biomarkers C-reactive Protein (CRP) | Day 89-90 | — |
| Interleukin 6 (IL-6) | Day 89-90 | — |
| Insulin Resistance (IR) | Day 89-90 | In each subject, an insulin resistance score based on Homeostasis Model Assessment (HOMA-IR) was estimated at day 89-90. Formula: fasting plasma glucose (mmol/l) times fasting serum insulin (mU/l) divided by 22.5. Low HOMA-IR values indicate high insulin sensitivity, whereas high HOMA-IR values indicate low insulin sensitivity (insulin resistance). |
Participant flow
Pre-assignment details
A total of 75 subjects signed consent and were enrolled in the study. Of these, 23 (31%) failed to qualify to participate in the study based on screening assessments, 12 (16%) withdrew consent prior to randomization, and 4 (5%) dropped out before randomization. As a result, 39 subjects were randomized.
Participants by arm
| Arm | Count |
|---|---|
| Ramelteon Subjects will take ramelteon 8mg one time daily 30 minutes before bedtime with approximately 8 ounces of water. Subjects have a 2 out of 3 chance of receiving ramelteon.
ramelteon | 26 |
| Placebo 15 subjects will be randomized to receive the placebo
placebo | 13 |
| Total | 39 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Physician Decision | 4 | 3 |
Baseline characteristics
| Characteristic | Ramelteon | Placebo | 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 | 26 Participants | 13 Participants | 39 Participants |
| Region of Enrollment United States | 26 participants | 13 participants | 39 participants |
| Sex: Female, Male Female | 16 Participants | 8 Participants | 24 Participants |
| Sex: Female, Male Male | 10 Participants | 5 Participants | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 8 / 26 | 3 / 13 |
| serious Total, serious adverse events | 0 / 26 | 0 / 13 |
Outcome results
Primary
Change in Metabolic Syndrome (MetSyn)
Time frame: Baseline, Day 30, Day 60, Day 89-90
Population: Data was not collected, and therefore not analyzed.
Primary
Mean Latency to Persistent Sleep (LPS) Via Polysomnography
Elapsed time from the beginning of the Polysomnography recording to the onset of the first 20 minutes of continuous sleep was measured.
Time frame: Day 89-90
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Ramelteon | Mean Latency to Persistent Sleep (LPS) Via Polysomnography | 19.2 minutes | Standard Deviation 11.3 |
| Placebo | Mean Latency to Persistent Sleep (LPS) Via Polysomnography | 48.6 minutes | Standard Deviation 33 |
Primary
Mean Latency to Persistent Sleep (LPS) Via Polysomnography
Elapsed time from the beginning of the Polysomnography recording to the onset of the first 20 minutes of continuous sleep was measured.
Time frame: Baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ramelteon | Mean Latency to Persistent Sleep (LPS) Via Polysomnography | 41.0 minutes | Standard Deviation 25.4 |
| Placebo | Mean Latency to Persistent Sleep (LPS) Via Polysomnography | 46.3 minutes | Standard Deviation 20.1 |
Primary
Sleep Onset Latency (SOL) as Measured by Pittsburgh Sleep Qualtiy Index (PSQI)
Subjects completed component 2 of the PSQI questionnaire. Component 2 asks questions about sleep latency and is scored on a scale from 0 (better) to 3 (worse).
Time frame: day 89 - 90
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Ramelteon | Sleep Onset Latency (SOL) as Measured by Pittsburgh Sleep Qualtiy Index (PSQI) | 1.72 units on a scale | Standard Deviation 0.9 |
| Placebo | Sleep Onset Latency (SOL) as Measured by Pittsburgh Sleep Qualtiy Index (PSQI) | 0.93 units on a scale | Standard Deviation 1.1 |
Primary
Sleep Onset Latency (SOL) as Measured by Pittsburgh Sleep Qualtiy Index (PSQI)
Subjects completed component 2 of the PSQI questionnaire. Component 2 asks questions about sleep latency and is scored on a scale from 0 (better) to 3 (worse).
Time frame: baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ramelteon | Sleep Onset Latency (SOL) as Measured by Pittsburgh Sleep Qualtiy Index (PSQI) | 2.5 units on a scale | Standard Deviation 0.7 |
| Placebo | Sleep Onset Latency (SOL) as Measured by Pittsburgh Sleep Qualtiy Index (PSQI) | 2.8 units on a scale | Standard Deviation 0.6 |
Primary
Sleep Onset Latency (SOL) as Measured by Self Report (Sleep Diary)
The average of a week of sleep onset latency data from the sleep diary filled out in the morning by the participating subjects. Sleep latency is defined as the length of time it takes from lying down for the night until sleep onset.
Time frame: Day 89-90
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Ramelteon | Sleep Onset Latency (SOL) as Measured by Self Report (Sleep Diary) | 29.7 minutes | Standard Deviation 21.7 |
| Placebo | Sleep Onset Latency (SOL) as Measured by Self Report (Sleep Diary) | 24.8 minutes | Standard Deviation 15.2 |
Primary
Sleep Onset Latency (SOL) as Measured by Self Report (Sleep Diary)
The average of a week of sleep onset latency data from the sleep diary filled out in the morning by the participating subjects.
Time frame: Baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ramelteon | Sleep Onset Latency (SOL) as Measured by Self Report (Sleep Diary) | 41.3 minutes | Standard Deviation 32.9 |
| Placebo | Sleep Onset Latency (SOL) as Measured by Self Report (Sleep Diary) | 38.8 minutes | Standard Deviation 19.8 |
Secondary
Change in Total Sleep Time
Change in sleep time will be determined by PSG.
Time frame: Day -1-0, Day 89-90
Population: Data was not collected, and therefore not analyzed.
Secondary
Inflammatory Biomarkers C-reactive Protein (CRP)
Time frame: Baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ramelteon | Inflammatory Biomarkers C-reactive Protein (CRP) | 11.8 mg/L | Standard Deviation 16.9 |
| Placebo | Inflammatory Biomarkers C-reactive Protein (CRP) | 26.1 mg/L | Standard Deviation 38.9 |
Secondary
Inflammatory Biomarkers C-reactive Protein (CRP)
Time frame: Day 89-90
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Ramelteon | Inflammatory Biomarkers C-reactive Protein (CRP) | 11.9 ng/mL | Standard Deviation 12.7 |
| Placebo | Inflammatory Biomarkers C-reactive Protein (CRP) | 7.3 ng/mL | Standard Deviation 28.1 |
Secondary
Insulin Resistance (IR)
In each subject, an insulin resistance score based on Homeostasis Model Assessment (HOMA-IR) was estimated at day 89-90. Formula: fasting plasma glucose (mmol/l) times fasting serum insulin (mU/l) divided by 22.5. Low HOMA-IR values indicate high insulin sensitivity, whereas high HOMA-IR values indicate low insulin sensitivity (insulin resistance).
Time frame: Day 89-90
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Ramelteon | Insulin Resistance (IR) | 12.6 HOMA-IR value | Standard Deviation 12.2 |
| Placebo | Insulin Resistance (IR) | 7.9 HOMA-IR value | Standard Deviation 6.6 |
Secondary
Insulin Resistance (IR)
In each subject, an insulin resistance score based on Homeostasis Model Assessment (HOMA-IR) was estimated at baseline. Formula: fasting plasma glucose (mmol/l) times fasting serum insulin (mU/l) divided by 22.5. Low HOMA-IR values indicate high insulin sensitivity, whereas high HOMA-IR values indicate low insulin sensitivity (insulin resistance).
Time frame: Baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ramelteon | Insulin Resistance (IR) | 16.9 HOMA-IR value | Standard Deviation 10.8 |
| Placebo | Insulin Resistance (IR) | 12.4 HOMA-IR value | Standard Deviation 9.2 |
Secondary
Interleukin 6 (IL-6)
Time frame: Day 89-90
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Ramelteon | Interleukin 6 (IL-6) | 2.2 pg/mL | Standard Deviation 1.4 |
| Placebo | Interleukin 6 (IL-6) | 1.3 pg/mL | Standard Deviation 1 |
Secondary
Interleukin 6 (IL-6)
Time frame: Baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ramelteon | Interleukin 6 (IL-6) | 1.6 pg/mL | Standard Deviation 1.1 |
| Placebo | Interleukin 6 (IL-6) | 2.5 pg/mL | Standard Deviation 2.4 |