Efficacy and Safety of Temazepam in HIV Seropositive Patients With Insomnia

Study Overview
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Brief Summary
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The purpose of this study is to test two study drugs, one of which is temazepam (15mg) and one of which is a placebo (an inactive substance that looks just like the temazepam), to see if insomnia (trouble sleeping) can be reduced in patients with HIV infection. Placebos are given in research studies to try and make sure that subjects are responding to the effects of the study drug and not to other factors, like the attention they are receiving. If you decide to take part in this study, you will take 1 capsule of study drug every night approximately 30 minutes before bedtime for approximately 12 weeks. This study is to test the study drug called temazepam for the treatment of insomnia (trouble sleeping) in patients with HIV infection. Temazepam has been approved by the FDA for the treatment of insomnia. However, because this study requires treatment for 12 weeks instead of the 7 to 10 days approved by the FDA, the use of temazepam is considered to be investigational in this study.

Official Title
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A Randomized, Double Blind, Placebo Controlled Study to Assess the Efficacy and Safety of Temazepam in HIV Seropositive Patients With Insomnia

Conditions
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Insomnia

Intervention / Treatment
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* Drug: Temazepam
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: males or females age 18-69; females must utilize an approved form of birth control during the study; have at least a 3 month history of insomnia as defined in the DSM-IV criteria for primary insomnia; self report > 60 minutes of wakefulness after initial sleep onset on at least 4 nights of 7 consecutive nights; self report > 30 minutes of self-reported latency to sleep onset on at least 4 nights of 7 consecutive nights; Self report < 6.5 hours of total sleep time at least 4 nights of 7 consecutive nights; be able to read, understand, and sign an informed consent form before entering into the study and must be willing to comply with all study procedures; agree to participate for the entire study period (a total of approximately 6 months); and provide documentation of HIV seropositivity and be enrolled in ongoing care for their HIV disease in an infectious disease clinic with their last examination not exceeding 3 months prior to screening date Exclusion Criteria: Have a clinically significant unstable medical abnormality, or history or presence of significant neurological disorders (including cognitive disorders), or frequent nightly urination, defined as > 2 times per night; Had a clinically significant illness, as determined by the Investigator, within 30 days of Initial Screening (Visit 1); Have any clinically significant abnormal finding in physical examination, neurological assessment, or vital signs, as determined by the Investigator; Have a known or exaggerated pharmacological sensitivity or hypersensitivity or intolerance to doxepin HCl, any tricyclic antidepressant or antihistamine, temazepam or any benzodiazepine; Have a positive urine drug screen for amphetamines, benzodiazepines, barbiturates, cocaine, opiates, or cannabinoids at Initial Screening (Visit 1); Self reports typical consumption of more than five alcoholic beverages on a single day or greater than 14 alcoholic beverages weekly; Have a history of epilepsy or serious head injury; Have been on current HAART or antiretroviral regimen for less than 1 month; Have a recent history (within one year) of alcohol or drug abuse, or current evidence of substance dependence or abuse as defined by DSM-IV-TR criteria; Have used temazepam for any indication within the 30 days prior to Initial Screening (Visit 1); Have used any investigational drug within 30 days or five half-lives (whichever is longer) prior to Initial Screening (Visit 1), or plans to use an investigational drug (other than the study drug) during the study; Current use of any of the following medications: antipsychotics, appetite suppressants, systemic corticosteroids, theophylline, respiratory stimulants and decongestants; The following medications may be discontinued for the purpose of entry into the study provided the medication is taken at bedtime for the indication of sleep. If the indication is other than sleep, the medication cannot be discontinued for the purpose of entry into the study: anxiolytics, antidepressants, anticonvulsants, histamine-1 receptor antagonists (except for loratadine, desloratidine, and fexofenadine), narcotic analgesics, sedative/hypnotics (other than study drug) or OTC sleep aids; Have symptoms consistent with the diagnosis of any other sleep disorder other than primary insomnia (e.g., sleep apnea, narcolepsy, periodic leg movements, restless leg syndrome, etc.); Have a body mass index (BMI) greater than or equal to 34; Have insomnia associated with circadian rhythm disturbances, such as night or rotating shift work or travel across more than four time zones in the 14 days before Initial Screening (Visit 1) or during the study; Self reports intentional napping more than two times per week; Have a variation in bedtime of more than three hours on five of seven consecutive nights as recorded on the sleep diary; Have a history of non-adherence to treatment or clinical visit attendance; or, subjects taking any benzodiazepine within 5 half-lives prior to the study baseline

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 69 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: temazepam<br>After screening, all subjects meeting entry criteria will be placed on the same single blind study drug treatment, asked to complete a daily sleep diary, and return one week later. After one week subjects randomized to temazepam will be given temazepam 15 mg for 12 weeks. | Drug: Temazepam<br>* Temazepam 15 mg orally at bedtime<br>|
| Placebo Comparator: Placebo<br>After screening, all subjects meeting entry criteria will be placed on the same single blind study drug treatment, asked to complete a daily sleep diary, and return one week later. After one week subjects randomized to placebo will be given placebo for 12 weeks. | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change in the Insomnia Severity Index | Mean change in the total score of the Insomnia Severity Index from Randomization to Final Study Visit after 12 weeks of double blind, placebo controlled dosing. The Insomnia Severity Index (ISI), is a 7-item questionnaire on a Likhert scale (0-4) assessing sleep initiation, sleep maintenance, satisfaction/distress over sleep problems, and daytime dysfunction. Responses to each item are summed to obtain a total score to determine the severity of insomnia. The total score can range from 0 to 28 with higher scores indicating greater insomnia severity. | Randomization to final study visit, approximately 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change in Self Reported Total Sleep Time | Mean change in self reported Total Sleep Time from Randomization to Final Study Visit in the placebo-controlled phase. | Randomization to final study visit, approximately 12 weeks | 
| Mean Change in Self-reported Total Sleep Time | Mean change in self-reported total sleep time from randomization to the end of the open label phase | Randomization to the end of the open label phase, approximately 1 week | 
| Mean Change in Piper Fatigue Score | A multidimensional scale for measuring fatigue, whose validity and reliability have been established across many patient populations including cancer patients, HIV, pregnancy, and myocardial infarction. There are 22 questions, in 3 subscales that measure behavioral, affective meaning, sensory and cognitive/mood aspects of fatigue, each scored on an 11-point likhert scale with a score of 0-10, 0 indicating no fatigue and 10 indicating the most severe fatigue. The Piper Fatigue Scale can range from 0 to 220 with higher scores indicating greater fatigue. | Baseline, week 12 | 
| Mean Change in the Hospital Anxiety and Depression Scale - Anxiety (HADS-A) | A scale designed to detect states of anxiety and depression in the setting of an outpatient clinic, that consists of 2 sets: the HADS-A (Anxiety) and HADS-D (Depression). This is a series of 7 questions in each set (for a total of 14), assessed on a scale from 0-4, 0 being the response that indicates the least anxiety or depression, and 4 the most. Separate scores are calculated for anxiety and depression and a score (ranging from 0 to 21) is obtained for each subscale. The higher the score, the more severe the anxiety or depression. | Baseline, week 12 | 
| Mean Change in the Distress Thermometer | A clinical tool that has been validated widely especially in cancer patients, to detect clinically significant emotional distress. This is a one-item scale that asks participants to rate their distress on scale from 0-100. Lower scores represent less distress and higher scores indicate greater distress. | Baseline, week 12 | 
| Mean Change in the Hospital Anxiety and Depression Scale - Depression (HADS-D) | A scale designed to detect states of anxiety and depression in the setting of an outpatient clinic, that consists of 2 sets: the HADS-A (Anxiety) and HADS-D (Depression). This is a series of 7 questions in each set (for a total of 14), assessed on a scale from 0-4, 0 being the response that indicates the least anxiety or depression, and 4 the most. Separate scores are calculated for anxiety and depression and a score (ranging from 0 to 21) is obtained for each subscale. The higher the score, the more severe the anxiety or depression. | Baseline, week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV, Insomnia