Effectiveness of BBT-I and Zopiclone for Chronic Insomnia

Study Overview
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Brief Summary
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Background: Importance of chronic insomnia (CI) problem is determined by its high prevalence rate, comorbidity and resistance to the treatment. Although cognitive behavior treatment of insomnia (CBT-I) remains the recommended treatment for CI it has disadvantages of time consuming and low treatment response. Hence shortened and simplified behavioral approaches such as Brief Behavioral therapy of insomnia (BBT-I) are developed. The aim of the present study is to test the effectiveness of BBT-I program for chronic insomnia in comparison with zopiclone in Russian population. The anthropometric, psychological and polysomnographic characteristics of patients were measured to find predictors of effectiveness of each method. Participants: 42 adults (14 males, 28 females, mean age 54 years) meeting the criteria for CI according International classification of sleep disorders-3 Methods: Participants were randomized into two groups. Each group passed 2-week courses of treatment by brief behavior treatment of insomnia (BBT-I) and zopiclone in different orders with 2-week washout period between the courses. Participants underwent in-lab polysomnography prior to the treatment and completed questionnaires (Insomnia Severity Index (ISI), Dysfunctional beliefs about sleep scale (DBAS), Beck Depression Inventory (BDI) and others) in the beginning and the end of each course

Detailed Description
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The study had a crossover design implying that every patient underwent two different treatment courses in random sequence: hypnotic or structured educational program (BBT-I) delivered in two sessions. Each treatment course was separated by 2-weeks washout period that provided the opportunity to evaluate the sustainability of treatment effect. Before and after each treatment course and after each washout period subjects completed set of questionnaires. The total duration of the study was 8 weeks in which 6 visits including 1 night polysomnography (PSG), 2 face-to-face structured educational program sessions and 5 diagnostic interviews have been performed. Participants A sample of 42 adults (14 males, 28 females, mean age 54 years from 29 to 80 years) meeting the criteria for chronic insomnia according ICSD-3 was recruited from outpatient care of Department of sleep medicine of University Hospital №3 of I.M. Sechenov First Moscow State Medical University. All participants were informed about the nature, purpose, risks, and discomforts that could arise from their participation, and about their right to withdraw at any time. Subjects documented their willingness to participate by signing the informed consent form, approved by local Ethic Committee. Treatment methods. BBT-I program includes two weekly one hour individual sessions; Hypnotic (zopiclone) in a dose of 7,5 mg has to be taken 30 minutes before bedtime for two weeks Measures Questionnaires. During the first visit patients underwent structured clinical interview and filled in self-report questionnaires: Beck Depression Inventory (BDI), State-trait anxiety inventory (STAI), Toronto Alexithymia Scale - short version (TAS-20) , Big Five Questionnaire (BFQ-2R), Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Index (ISI), Dysfunctional beliefs about sleep scale (DBAS), Sleep hygiene index (SHI). During the next 4 visits participants repeatedly underwent diagnostic tests included BDI, STAI, PSQI, ISI, DBAS, SHI. Participants kept daily sleep diaries where they recorded bedtime and morning rise time, sleep onset latency (SOL), number of night awakenings and time of wakefulness after sleep onset before waking up (WASO) for the whole study period. On the last visit participants completed questionnaire for assessment of effectiveness of treatment along with diagnostic routine. Patients were asked to rank the effectiveness of proposed methods of treatment (didactic presentation, stimulus control, sleep restriction, relaxing recording and zopiclone) in ascending order from 1 to 5 points (5 seems most effective). Polysomnography. Participants underwent in-lab PSG (1 night without adaptation night) prior to the treatment in order to exclude other disorders producing subjective sleep complaints (sleep apnea, periodic limb movements disorder). Standard polysomnography montage including 6 monopolar electroencephalography (EEG) channels; 1 submental electromyogram (EMG) channel; 2 electrooculogram (EOG) channels; 2 EMG channels of the right and left tibialis anterior muscles; 1 electrocardiogram channel; oronasal airflow pressure; thoracic and abdominal efforts; respiratory sound; oxygen saturation; body position with videomonitoring was performed. The objective sleep measures included total sleep time (TST), sleep-onset latency, wake time after sleep onset (WASO), number of awakenings, sleep efficiency (the ratio of TST to time spent in bed multiplied on 100%, SE), percentage of sleep stages. PSG data were analysed according the 2007 American Academy of Sleep Medicine criteria including its revision in 2012.

Official Title
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Effectiveness of Nonspecific Methods of Treatment and Zopiclone for Chronic Insomnia

Conditions
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Insomnia Chronic

Intervention / Treatment
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* Behavioral: Brief behavioral therapy
* Drug: Zopiclone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: meeting the criteria for chronic insomnia according ICSD-3 willingness to take part in the study and signed informed consent form Exclusion Criteria: unability to stop taking medications that have a proven impact on sleep at least one week before and during the study; history of alcohol or drug abuse; major depressive disorder or other severe mental disorder identified by a clinical assessment and medical history; dementia; pregnancy or lactation; shift or night work; medical problems that would be a direct cause of sleep complaints: moderate/severe sleep apnea, defined as an apnea-hypopnea index of ≥15 events per hour, periodic limb movement disorder defined as a periodic leg movement index ≥15 events per hour or restless legs syndrome; other serious chronic conditions or exacerbation of chronic disorder preventing further participation.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Crossover Assignment
Interventional Model Description: Study design implied that every patient underwent two different treatment courses in random sequence: hypnotic or structured educational program (BBT-I) delivered in two sessions. Subjects were randomly assigned to one of treatment sequences by card sorting method. Patients of the zopiclone-first group underwent the medication therapy for the first two weeks followed by educational program. Patients of the BBT-I-first group received two-week educational program followed by medication therapy. Each treatment course was separated by 2-weeks washout period that provided the opportunity to evaluate the sustainability of treatment effect. Before and after each treatment course and after each washout period subjects completed set of questionnaires.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: zopiclone first group<br>underwent the medication therapy (zopiclone) for the first two weeks followed by brief behavioral therapy | Behavioral: Brief behavioral therapy<br>* program included a question-and-answer part; a didactic presentation of sleep regulation mechanisms; the review of causes of onset and chronification of illness; an examination of patient's sleep log; explanation of sleep restriction method and prescription of individual regimen of sleep; explanation of stimulus control method; sleep hygiene education; discussion of relaxation techniques. Participants were supplied with 32 minute audio recording Relaxation and refreshment session for insomnia created for this study by Dr. A.Tabidze with verbal relaxing instructions with quiet musical composition behind it. Participants were instructed to listen to this recording in headphones each day for 2-week BBT-I period after laying into bed and turning the light off.<br>* Other names: BBT-I;Drug: Zopiclone<br>* zopiclone intake in a dose of 7,5 mg 30 minutes before bedtime for two weeks<br>* Other names: hypnotic;|
| Experimental: BBT-I first group<br>received two-week brief behavioral therapy followed by medication therapy (zopiclone). | Behavioral: Brief behavioral therapy<br>* program included a question-and-answer part; a didactic presentation of sleep regulation mechanisms; the review of causes of onset and chronification of illness; an examination of patient's sleep log; explanation of sleep restriction method and prescription of individual regimen of sleep; explanation of stimulus control method; sleep hygiene education; discussion of relaxation techniques. Participants were supplied with 32 minute audio recording Relaxation and refreshment session for insomnia created for this study by Dr. A.Tabidze with verbal relaxing instructions with quiet musical composition behind it. Participants were instructed to listen to this recording in headphones each day for 2-week BBT-I period after laying into bed and turning the light off.<br>* Other names: BBT-I;Drug: Zopiclone<br>* zopiclone intake in a dose of 7,5 mg 30 minutes before bedtime for two weeks<br>* Other names: hypnotic;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Insomnia Severity Index | self reported insomnia symptoms severity by Insomnia severity index . Each item is scored 0 (no problem) - 4 (very big problem) with total between 0-28 (absence of insomnia (0-7); sub-threshold insomnia (8-14); moderate insomnia (15-21); and severe insomnia (22-28). | For BBT-I-first group: on the initial examination (Day 1/Week 1/Month 1), after first treatment course (Day 14/Week 2/Month 1); For zopiclone-first group: after washout period (Day 28/Week 4/Month 1) after second treatment course (Day 42/Week 6/Month 2) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Beck Depression Inventory | 21-item questionnaire assessing (on 4-point Likert scales) the intensity of depressive symptoms in the past week. Minimum score 0, maximum score 63 points. Higher total score represents more severe depressive symptoms | on the initial examination (Day 1/Week 1/Month 1), after first treatment course (Day 14/Week 2/ Month 1), after washout period (Day 28/ Week 4/Month 1), after second treatment course (Day 42/Week 6/Month 8), after second washout (Day 56/Week 8/ Month 2) | 
| State Anxiety Subscale (STAI) | State trait anxiety scale is a 2-part questionnaire assessing state (situational) and trait anxiety. State anxiety subscale comprise 20 items rated on a 4-point Likert scale. Minimum score for subscale is 20 and maximum score is 80 points. Higher total score indicates more severe anxiety symptoms | on the initial examination (Day 1/Week 1/Month 1), after first treatment course (Day 14/Week 2/ Month 1), after washout period (Day 28/ Week 4/Month 1), after second treatment course (Day 42/Week 6/Month 8), after second washout (Day 56/Week 8/ Month 2) | 
| Dysfunctional Beliefs About Sleep Scale | questionnaire assessing sleep related cognitions in 16 item rated on a 10-point Likert scale. Minimum score is 0, maximum score is 160 points. Higher total score represents more intensive disfunctional beliefs | on the initial examination (Day 1/Week 1/Month 1), after first treatment course (Day 14/Week 2/ Month 1), after washout period (Day 28/ Week 4/Month 1), after second treatment course (Day 42/Week 6/Month 8), after second washout (Day 56/Week 8/ Month 2) | 
| Sleep Hygiene Index | questionnaire assessing sleep related behavior in 13 item rated on a 5-point Likert scale.Minimum score 13 points and maximum score 65 points. Higher total score represents worse sleep hygiene | on the initial examination (Day 1/Week 1/Month 1), after first treatment course (Day 14/Week 2/ Month 1), after washout period (Day 28/ Week 4/Month 1), after second treatment course (Day 42/Week 6/Month 8), after second washout (Day 56/Week 8/ Month 2) | 
| Pittsburgh Sleep Quality Index | 19-item questionnaire evaluating sleep quality over the past month. The first 4 items are open questions, items 5 to 19 are rated on a 4-point Likert scale. A total score range from 0 to 21. A score > 5 suggests poor sleep quality. | on the initial examination (Day 1/Week 1/Month 1), after first treatment course (Day 14/Week 2/ Month 1), after washout period (Day 28/ Week 4/Month 1), after second treatment course (Day 42/Week 6/Month 8), after second washout (Day 56/Week 8/ Month 2) | 
| Trait Anxiety Subscale (STAI) | STAI is a 2-part questionnaire assessing state (situational) and trait anxiety. Trait anxiety subscale comprise 20 items rated on a 4-point Likert scale. Minimum score for each subscale is 20 and maximum score is 80 points. Higher total score indicates more severe anxiety symptoms | on the initial examination (Day 1/Week 1/Month 1), after first treatment course (Day 14/Week 2/ Month 1), after washout period (Day 28/ Week 4/Month 1), after second treatment course (Day 42/Week 6/Month 8), after second washout (Day 56/Week 8/ Month 2) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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chronic insomnia, brief behavioral treatment, behavioral treatment, insomnia severity index, predictors, treatment response