Insomnia, Primary Insomnia, Psychophysiologic Insomnia
Conditions
Keywords
Insomnia, Sleep, zolpidem, Ambien, Hypnotics
Brief summary
We want to assess whether how and when one takes sleep medication results in similar or different outcomes with respect to symptom relief. We also want to know whether taking medication for a period of time provides continued benefit once the medication is stopped.
Detailed description
To date, the aggressive treatment (Tx) of chronic insomnia has been evaluated in terms of whether maintenance therapy is possible. While what constitutes maintenance therapy is a matter of debate, there are two studies which show that benzodiazepine receptor agonists (BZRAs) 1) are effective when used intermittently for up to 3 months and 2) may be used on a nightly basis for up to 6 months with no loss of efficacy. The significance of the present research is two fold. First, it will allow us to compare the two primary strategies used for long term treat of insomnia (nightly dosing vs intermittent dosing). Second, it will allow an evaluation of the possibility that extended treatment, given careful withdrawal from medication, may yield long term clinical gains. Re: Objective 1: It is widely assumed that intermittent dosing confers increased efficacy. That is, less frequent medication use will extend the duration of time for which the medication is maximally potent. An empirical assessment of this proposition is required. If incorrect, physicians and patients should be encouraged to adopt a more aggressive approach to treatment. If correct, physicians and patients should be encouraged to adopt the intermittent dosing approach to treatment. Re: Objective 2: It is widely assumed that treatment with sedatives (sleep promoting medications) constitutes only palliative care. An empirical assessment of this proposition is required. If correct, physicians and patients should be encouraged to adopt a more aggressive approach to long term treatment. If incorrect, physicians and patients should be encouraged to adopt an approach to treatment that is not currently a standard of practice: extended treatment with a clear plan to taper medication that is designed to maintain the clinical gains that occurred with medication use. We propose to evaluate the above issues in a pilot study of 40 subjects with Primary Insomnia where subjects are randomized to one of 4 conditions: 1. QHS dosing with placebo 2. QHS dosing with 10mg of zolpidem 3. Intermittent dosing with 10mg of zolpidem (3-5 pills per week as needed) 4. Monitor only condition.
Interventions
DRUGZolpidem
10 mg of Zolpidem
DRUGSugar Pill
Sponsors
Sanofi-Synthelabo
University of Rochester
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
25 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
* Ages 25 - 55 * a stable sleep/wake schedule with a preferred sleep phase between 10:00 p.m. and 8:00 a.m. * Patients with Primary Insomnia will meet diagnostic criteria for Psychophysiologic Insomnia according to the International Classification of Sleep Disorders manual (ICSD). * complaint of disturbed sleep must have the following characteristics: \>30 minutes to fall asleep, and/or \>30 minutes wake after sleep onset time, a total sleep time of no more than 6.5 hours (or a sleep efficiency of less than 85%), a problem frequency of \>4 nights/ week and a problem duration \>6 months.
Exclusion criteria
* Unstable medical or psychiatric illness * Use of medication that may cause insomnia or may be reduce the effectiveness of zolpidem (e.g. selective serotonin reuptake inhibitors(SSRI's), steroids, bronchodilators, calcium channel blockers, beta blockers, etc.) * symptoms suggestive of sleep disorders other than insomnia * polysomnographic data indicating sleep disorders other than insomnia * Evidence of active illicit substance use or fitting criteria for alcohol abuse or dependence * inadequate language comprehension * pregnancy * first-degree relatives with bipolar disorder or schizophrenia
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Sleep Latency (SL) | Baseline and Post-treatment (12wks) | Number of subjects with any reduction in SL (time to fall asleep in minutes)at post-tx compared to baseline where mean SL = mean of daily values for one week calculated from sleep diary values. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Wake After Sleep Onset (WASO) | Baseline and Post-Treatment (12 weeks) | Number of subjects with any reduction in WASO at post-tx compared to baseline where mean WASO = mean of daily values for one week calculated from sleep diary values. |
Countries
United States
Participant flow
Recruitment details
Subjects recruited from television and newspaper ads. After a telephone or web based screening, subjects brought into the lab to read the Informed Consent Form (ICF). After the ICF has been signed, an initial medical and psychiatric evaluation completed. If the subjects remain eligible they are required to keep two weeks of sleep diaries.
Participants by arm
| Arm | Count |
|---|---|
| Placebo QHS dosing with placebo | 5 |
| QHS Zolpidem QHS dosing with 10mg of zolpidem | 5 |
| Intermittant Zolpidem Intermittent dosing with 10mg of zolpidem (3-5 pills per week as needed | 5 |
| CTRL Monitor only condition. | 5 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Failed Screening | 1 | 0 | 1 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 0 | 1 |
| Overall Study | Withdrawn - Medication Expiration | 0 | 2 | 1 | 0 |
Baseline characteristics
| Characteristic | Placebo | QHS Zolpidem | Intermittant Zolpidem | CTRL | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants | 5 Participants | 5 Participants | 5 Participants | 20 Participants |
| Sex: Female, Male Female | 4 Participants | 3 Participants | 3 Participants | 4 Participants | 14 Participants |
| Sex: Female, Male Male | 1 Participants | 2 Participants | 2 Participants | 1 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 5 | 0 / 5 | 0 / 5 | 0 / 5 |
| serious Total, serious adverse events | 0 / 5 | 0 / 5 | 0 / 5 | 0 / 5 |
Outcome results
Primary
Sleep Latency (SL)
Number of subjects with any reduction in SL (time to fall asleep in minutes)at post-tx compared to baseline where mean SL = mean of daily values for one week calculated from sleep diary values.
Time frame: Baseline and Post-treatment (12wks)
Population: Completers Only
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Sleep Latency (SL) | 1 participants |
| QHS Zolpidem | Sleep Latency (SL) | 2 participants |
| Intermittant Zolpidem | Sleep Latency (SL) | 3 participants |
| CTRL | Sleep Latency (SL) | 0 participants |
Secondary
Wake After Sleep Onset (WASO)
Number of subjects with any reduction in WASO at post-tx compared to baseline where mean WASO = mean of daily values for one week calculated from sleep diary values.
Time frame: Baseline and Post-Treatment (12 weeks)
Population: Completers
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Wake After Sleep Onset (WASO) | 1 participants |
| QHS Zolpidem | Wake After Sleep Onset (WASO) | 2 participants |
| Intermittant Zolpidem | Wake After Sleep Onset (WASO) | 2 participants |
| CTRL | Wake After Sleep Onset (WASO) | 1 participants |