Clinical trial NCT04050176: Use of Blinded Tapering for Hypnotic Discontinuation
Official title: Use of Blinded Tapering for Hypnotic Discontinuation
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Hypnotic Dependence Among Those With Insomnia
Keywords: insomnia
sedative hypnotics
hypnotic tapering
Lead sponsor: National Jewish Health
Sponsor class: OTHER
Collaborators: name: National Institute on Drug Abuse (NIDA)
First posted: 2019-08-08
Enrollment: 260
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Two groups: Blinded and Unblinded.
Primary purpose: TREATMENT

Brief summary: The study will employ a randomized longitudinal clinical trial design to evaluate the relative efficacy of a blinded hypnotic tapering protocol when used in combination with therapist delivered Cognitive Behavioral Therapy for Insomnia (CBTI) for enhancing hypnotic discontinuation rates. A blinded SMT+CBTI intervention will be compared to open-label SMT+CBTI.

Detailed description: Treatment-seeking insomnia sufferers most often present in primary care venues where the first and usually only treatment is a prescription for a sedative hypnotic, typically a benzodiazepine (BZD) or newer benzodiazepine receptor agonist (BzRA). For some patients, short-term or intermittent hypnotic use provides satisfactory insomnia relief. However, more than 65% of individuals who are prescribed hypnotics use them for more than a year, and \> 30% remain on these agents for more than five years. Whereas some patients may appreciate partial or full relief of insomnia symptoms with ongoing hypnotic use, continuous long-term use of these agents may not represent optimal therapy. Many insomnia patients who participate in non-drug insomnia therapy such as cognitive behavioral insomnia therapy (CBT-I) achieve sustained insomnia remission long after a time-limited course of treatment. However, it is difficult for most long-term hypnotic users to convert from use of medications to a self-management approach. Interventions that combine CBT-I with supervised medication tapering (SMT) have shown the greatest promise for achieving this outcome, but almost 50% of patients who receive this assistance either fail to discontinue their hypnotics or return to them even if they do achieve short-term abstinence. Our clinical and research observations suggest that psychological factors including sleep-related performance anxiety, low sleep-related self-efficacy and beliefs about needs for medications interact to lead to difficulties abstaining from hypnotic use. Moreover, our highly promising pilot data suggest that such factors may be mitigated by use of a blinded SMT protocol which appears to increase rates of medication abstinence. The current project will use a 2 x 4 randomized longitudinal clinical trial design to test the relative efficacy of our highly promising blinded tapering protocol, vis a vis open-label tapering, when combined with therapist delivered CBT-I. A sample of 260 will be enrolled, complete pre-intervention baseline measures and then be randomly assigned to: (1) a blinded hypnotic SMT + therapist delivered CBT-I; or (2) open-label tapering + CBT-I. During treatment all enrollees will first receive one on one treatment sessions with a trained CBT-I therapist over a 6 week period while maintaining baseline doses of their respective hypnotics. They then will begin a 10 week SMT during which they are provided a blinded or open-label tapering SMT protocol. During this phase they will have their hypnotic medication doses reduced by 25% every two weeks. Immediately after completing the SMT and again at 3- and 6-month follow-ups they will complete study outcome measures. The primary study outcome will be hypnotic discontinuance rates of the two treatment groups. Secondary outcomes include nights of hypnotic use per week, nightly average dosage of hypnotic used in diazepam equivalents as well as scores on sleep quality, daytime fatigue and quality of life. This study will lead to refining guidelines for tapering methods and providing a better understanding of treatment outcome predictors so as to provide more successful, person-centered interventions.

Eligibility criteria: Inclusion Criteria:

1. be currently using one or more BZD or newer BzRA hypnotics at bedtime for insomnia management;
2. have been using one or more such agents at least 5 nights/week for at least the past 12 months;
3. express interest in discontinuing hypnotic use and learning to manage their insomnia without medications;
4. report one or more failed attempts to discontinue hypnotic use in the past;
5. provide written consent to participate.
6. have an insomnia severity index score \> 10 indicating at least mild insomnia symptoms without sleep medication

Exclusion Criteria:

1. an untreated, or unstable psychiatric disorder as suggested by current active symptoms or a medication regimen that has been changed within the past 2 months;
2. a lifetime diagnosis of any psychotic or bipolar disorder
3. an imminent risk for suicide
4. evidence of alcohol or drug abuse (other than hypnotics) within the past year, since such abuse patterns suggest specialized substance abuse treatment may be indicated
5. unstable or terminal physical illness (e.g., cancer), neurological degenerative disease (e.g., dementia) or sleep disruptive medical condition
6. current use of medications known to cause insomnia (e.g., corticosteroids)
7. screening evidence of circadian rhythm sleep disorder (e.g., delayed sleep phase syndrome) or other sleep disorder (e.g. narcolepsy, idiopathic hypersomnolence, Rapid Eye Movement (REM) behavior disorder) for which CBTI would not represent optimal therapy
8. habitual bedtimes later than 2:00 AM or rising times later than 10:00 AM;
9. consuming \> 2 alcoholic beverages/day or any cannabis products at least 5 times/week
10. pregnant women or mothers with care-taking responsibilities for infants due to the sleep-disruption caused by such circumstances
11. clinical or polysomnographic evidence of undiagnosed and untreated restless legs syndrome (RLS), sleep apnea or periodic limb movements (PLMS) that require alternative therapies and would limit participants' responses to CBTI

Primary outcomes:
measure: Hypnotic Discontinuation Rate As Assessed By Analysis of Study Pharmaceutical Records
timeFrame: 10-week tapering phase
Secondary outcomes:
measure: Nights of Hypnotic use/week
timeFrame: Six-month follow up phase
measure: Weekly average dosage of hypnotic used in diazepam equivalents
timeFrame: Six-month follow up phase
measure: Use of over the counter sleep aids (e.g. Benadryl) as well as use of substances (alcohol, marijuana)
timeFrame: Six-month follow up phase
Other outcomes:
Locations:
city: Denver
country: United States
facility: National Jewish Health
state: Colorado
Study officials:
affiliation: National Jewish Health
name: Jack D Edinger, Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: National Jewish Health
name: Fredrick Wamboldt, M.D.
role: PRINCIPAL_INVESTIGATOR
References: