Clinical trial NCT03339583: Effectiveness of BBT-I and Zopiclone for Chronic Insomnia
Official title: Effectiveness of Nonspecific Methods of Treatment and Zopiclone for Chronic Insomnia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Insomnia Chronic
Keywords: chronic insomnia
brief behavioral treatment
behavioral treatment
insomnia severity index
predictors
treatment response
Lead sponsor: I.M. Sechenov First Moscow State Medical University
Sponsor class: OTHER
First posted: 2017-11-13
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention 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.
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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:

1. unability to stop taking medications that have a proven impact on sleep at least one week before and during the study;
2. history of alcohol or drug abuse;
3. major depressive disorder or other severe mental disorder identified by a clinical assessment and medical history;
4. dementia;
5. pregnancy or lactation;
6. shift or night work;
7. 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;
8. other serious chronic conditions or exacerbation of chronic disorder preventing further participation.

Primary outcomes:
measure: Insomnia Severity Index
timeFrame: 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 outcomes:
measure: Beck Depression Inventory
timeFrame: 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)
measure: State Anxiety Subscale (STAI)
timeFrame: 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)
measure: Dysfunctional Beliefs About Sleep Scale
timeFrame: 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)
measure: Sleep Hygiene Index
timeFrame: 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)
measure: Pittsburgh Sleep Quality Index
timeFrame: 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)
measure: Trait Anxiety Subscale (STAI)
timeFrame: 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)
Other outcomes:
measure: Toronto Alexithymia Scale (TAS-20)
timeFrame: once at baseline assessment
measure: Sleep Latency
timeFrame: once at baseline assessment
measure: Total Sleep Time
timeFrame: once at baseline assessment
measure: Sleep Efficiency
timeFrame: once at baseline assessment
measure: Wake After Sleep Onset
timeFrame: once at baseline assessment
measure: Amount of Awakenings
timeFrame: once at baseline assessment
measure: N1 NREM Sleep Percentage
timeFrame: once at baseline assessment
measure: N2 NREM Sleep Percentage
timeFrame: once at baseline assessment
measure: N3 NREM Sleep Percentage
timeFrame: once at baseline assessment
measure: REM Sleep Percentage
timeFrame: once at baseline assessment
Locations:
Study officials:
affiliation: I.M. Sechenov First Moscow State Medical University
name: Polina Pchelina, PG student
role: PRINCIPAL_INVESTIGATOR
References:
citation: Pchelina PV, Tabidze AA, Poluektov MG. [Comparative study of effectiveness of cognitive-behavior therapy and zopiclone for chronic insomnia]. Zh Nevrol Psikhiatr Im S S Korsakova. 2017;117(4. Vyp. 2):48-55. doi: 10.17116/jnevro20171174248-55. Russian.