Chronic Insomnia
Conditions
Keywords
Chronic insomnia, Ramelteon, Rozerem, dose reduction
Brief summary
To investigate effects on combination use of Ramelteon in the dose reduction or interruption process of (non-)BZD hypnotics during the dose reduction or interruption algorithm.
Detailed description
The hypnotic 'Ramelteon' does not have effect on Gamma Aminobutyric Acid (GABA-A) receptor that relates to the formation of addiction to the BZD or non-BZD hypnotics. Some results of clinical trials has been reported that the dose reduction or interruption of (non-)BZD hypnotics was achieved on combination use of Ramelteon by using its characteristic of the action mechanism with safely and effectively. However, these results have not been confirmed with randomized controlled trials.
Interventions
DRUGRamelteon 8mg
Ramelteon 8mg once daily before bedtime for 12 weeks since informed consent
DRUGPlacebo
Placebo capsule once daily before bedtime for 12 weeks since informed consent
Sponsors
Yoyogi Sleep Disorder Clinic, Foundation of Sleep and Health Science
Translational Research Center for Medical Innovation, Kobe, Hyogo, Japan
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Subjects meeting Criteria 1 or 2 and Criteria 3 and all subsequent criteria will be included in the study: 1. Patients diagnosed as chronic insomnia having sleep onset disturbance, and with a duration of the disease of at least 6 months 2. Patients diagnosed with chronic insomnia comorbid with mood disorders (depression or bipolar disorder) can be included to this study if they have remission of mood symptoms. 3. Patients taking (non-)BZD hypnotics (including etizolam at bedtime) at a fixed dose in the following patterns since at least 1 month prior to consent (over 90% of drug compliance should be confirmed at the time of medical interview): * Patients taking 2 drugs at the usual dose (1 unit) * Patients taking 3 drugs at the usual dose (1 unit) * Patients taking 4 drugs at the usual dose (1 unit) * Patients taking a drug at 2-fold of the usual dose (2 units) * Patients taking a drug at 2-fold of the usual dose (2 units) and a drug at the usual dose (1 unit) * Patients taking a drug at 2-fold of the usual dose (2 units) and 2 drugs at the usual dose (1 unit) * Patients taking 2 drugs at 2-fold of the usual dose (2 units) Patients whose total dosage are 2～4 units of 1～4 drugs can be also included. But attention needed not to conflict with
Exclusion criteria
2. ※Dosage cannot exceeded 2 units per 1 drug. * Patients whose symptoms of insomnia were stabilized, and the investigators determined that the (non-) BZD hypnotics could be reduced or discontinued * Patients aged 20 years or older at the time of consent * Patients who are willing to comply with algorithm for dose reduction and discontinuation * Patients who can understand the content of the study and provide consent to participate in the study in writing on their own will.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The achievement ratio of the 50% dose reduction of (non-)BZD hypnotics (Diazepam conversion value) at 12weeks or withdrawal without any deterioration of insomnia symptoms. | 12 weeks | Evaluate the achievement ratio of the 50% or more of dose reduction by Participant's diary |
| The rate of subjects who achieved more than 50% dose reduction of (non-)BZD hypnotics (Diazepam conversion value) at 12 weeks or withdrawal since informed consent. | 12 weeks | The rate of subjects who achieved more than 50% of dose reduction (Diazepam conversion value) will be assessed by Participant's diary |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The achievement ratio of the 100% dose reduction at 12weeks or withdrawal | 12 weeks | The achievement ratio of the 100% dose reduction will be assessed by Participant's diary |
| The variation in total score of Pittsburg Sleep Quality Index (PSQI) at 4weeks, 8weeks and 12weeks | at 0, 4, 8 and 12 weeks | The variation in total score of PSQI will be assessed by the PSQI value sets sets at week 0, 4, 8 and 12. (The range of total score is 0-21. Higher scores represent worse tendency of the symptoms.) |
| The variation in total score of Athens Insomnia Scale (AIS) at 4weeks, 8weeks and 12weeks | at 0, 4, 8 and 12 weeks | The variation in total score of AIS will be assessed by the AIS value sets at week 0, 4, 8 and 12. (The range of total score is 0-24. Higher scores represent worse tendency of the symptoms.) |
| The variation in Patient health questionnaire (PHQ-9) score at 4weeks, 8weeks and 12weeks | at 0, 4, 8 and 12 weeks | The variation in PHQ-9 score will be assessed by the PHQ-9 value sets at week 0, 4, 8 and 12. (The range of total score is 0-27. Higher scores represent worse tendency of the symptoms.) |
| The achievement ratio of the 50% dose reduction (Diazepam conversion value) at 4weeks and 8weeks | at 4 weeks and 8weeks | The rate of subjects who achieved more than 50% dose reduction (Diazepam conversion value) will be assessed by Participant's diary |
| Patient global impression of therapy (PGI) score at 12weeks or withdrawal | 12 weeks | PGI(Patient global impression of therapy) score will be assessed by the PGI value sets at 12weeks or withdrawal. (The range of total score is 0-21. Higher scores represent worse tendency of the symptoms.) |
| The variation in Ben-dep(Benzodiazepine Dependence Self-Report Questionnaire) score at 12weeks or withdrawal | at 0 and 12 weeks | The variation in Ben-dep score will be assessed by the Ben-dep value sets at 0 and 12weeks or withdrawal. (The range of total score is 0-100. Higher scores represent worse tendency of the symptoms.) |
| Adverse Events | 12 weeks | Adverse Events will be determined by the latest version of MedDRA/J （Medical Dictionary for Regulatory Activities/J). |
| Guide to the use of the clinical withdrawal assessment scale for benzodiazepines (CIWA-B) score at 4weeks, 8weeks and 12weeks | at 4, 8 and 12 weeks | The variation in CIWA-B (Guide to the use of the clinical withdrawal assessment scale for benzodiazepines) score will be assessed by the CIWA-B value sets at week 4, 8 and 12. (The range of total score is 0-80. Higher scores represent worse tendency of the symptoms.) |
| The average of the dose reduction rate at 4weeks, 8weeks and 12weeks | at 4 weeks, 8weeks and 12 weeks | The average of the dose reduction rate will be assessed by Participant's diary |
Countries
Japan
Outcome results
None listed