Baclofen for Improving Benzodiazepine Titration in Benzodiazepine Dependence
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 93
- 试验地点
- 2
- 主要终点
- Difference in total benzodiazepine consumption, in mg-diazepam
研究概览
简要总结
Benzodiazepines and related molecules are among the most prescribed psychotropic treatments in France and Europe. 13.4% of the French population had at least one reimbursement of benzodiazepines in 2015, which places France second in Europe.
However, the chronic use of benzodiazepines is a source of numerous complications, particularly addictive. To date, there is no authorized pharmacological treatment for benzodiazepine withdrawal.
Baclofen is a gamma-aminobutyric acid (GABA)-B agonist, a pharmacological receptor that regulates GABA-A, the target of benzodiazepines. The pharmacological mechanisms of baclofen are therefore related to those of benzodiazepines. Empirical use outside of the MA has shown that baclofen can facilitate the reduction of benzodiazepines in cases of severe addiction, but this pharmaceutical interest remains to be demonstrated in a comparative study.
The main objective of the project is to evaluate the efficacy of baclofen, compared to placebo, in reducing benzodiazepine doses in patients with benzodiazepine use disorder (BUD).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients aged ≥ 18 years to ≤ 65 years
- •For women of childbearing potential :
- •negative pregnancy test at inclusion
- •and use of effective contraception which will be continued throughout the trial period
- •and agrees to carry out pregnancy tests throughout the trial period.
- •BUD of any severity defined according to Diagnostic and Statistical Manual of Mental Disorders (DSM) 5 criteria
- •Average daily benzodiazepine dosage between 30 mg and 200 mg-diazepam (according to Ashton equivalence table) over the 28 days prior to inclusion. Benzodiazepine equivalents (zolpidem, zopiclone and eszopiclone) will be counted as part of the total equivalent daily dose of diazepam and will also be included in the tapering procedure.
- •Continued use of benzodiazepines for more than 12 weeks
- •At least one history of BUD treatment failure. A treatment failure is defined as a failure to withdraw from the full dose (i.e., discontinuation of benzodiazepine and related prescriptions) according to a previously established tapering schedule, by a general practitioner or specialist
- •Patient affiliated to a social security system.
- •Patients with or without guardianship
- •Patient capable of giving free, informed and written consent.
排除标准
- •Cirrhosis of the liver
- •Patients with significant medical conditions such as cancer, HIV, epilepsy, chronic respiratory failure, renal failure, etc.
- •Non-compatible health conditions (at the discretion of the investigator)
- •The following psychiatric conditions as defined by DSM-5 criteria: schizophrenic disorder, persistent delusional disorder, schizophreniform disorder, schizoaffective disorder, bipolar disorder, autism spectrum disorder identified using the Mini International Neuropsychiatric Interview version 7.0.2 (MINI 7.0.2)
- •Suicidal state identified using MINI 7.0.2
- •Dependence on substances or drugs other than benzodiazepines and nicotine (dependence will be identified through the use of MINI 7.0.2)
- •History of baclofen use for all indications
- •Unauthorized combination therapies will be: pregabalin, topiramate, ketamine, sodium oxybate, gabapentin, valproic acid, sodium valproate, melatonin, buspirone, hydroxyzine, propranolol, bisoprolol, etifoxin, carbamazepine, clonidine, paroxetine, all neuroleptic/antipsychotic class therapies, and tricyclic antidepressants
- •Pregnant or nursing women
- •Hypersensitivity to baclofen or microcrystalline cellulose.
- •Participants under guardianship
- •Patients who need to drive and/or use machines during the 1-week dose escalation phase
研究组 & 干预措施
Placebo
干预措施: Placebo (Drug)
Baclofen 30 microgram (mg) treatment
baclofen treatment (30 mg/per day)
干预措施: Baclofen 30 mg (Drug)
Baclofen 60 mg
baclofen treatment (60 mg/per day)
干预措施: Baclofen 60 mg (Drug)
结局指标
主要结局
Difference in total benzodiazepine consumption, in mg-diazepam
时间窗: between the 28 days before inclusion in the clinical trial and the last 28 days of the clinical trial
This difference will be compared between the two groups (winning baclofen group and placebo group). Total benzodiazepine consumption will be measured using the Benzodiazepine Timeline Follow-Back (B-TLFB). A mean value (in mg/d) for the 28 days of consumption will be calculated for each patient (between the 28 days prior to inclusion in the clinical trial and the last 28 days of the clinical trial).
次要结局
- Frequency of serious adverse events of special interest(through study completion, an average of 4 and a half months)
- Frequency of non-serious adverse events of special interest(through study completion, an average of 4 and a half months)
- Frequency of benzodiazepine discontinuation at the last visit of the treatment period by urine test(at study completion, an average of 4 and a half months)
- Frequency of benzodiazepine discontinuation at the last visit of the treatment period by B-TLFB questionnaire(at study completion, an average of 4 and a half months)
- Craving score assessed by the Visual Analog Scale (VAS)(up to visit 6, an average of 3 and a half months)
- frequency of all-cause study discontinuations(through study completion, an average of 4 and a half months)
- Frequency of benzodiazepine discontinuation at the last visit of the treatment period by the Clinical Institute Withdrawal Assessment of Benzodiazepine (CIWA-B) questionnaire(up to visit 6, an average of 3 and a half months)
- Anxiety symptoms assessed by the State Trait Inventory Anxiety (STAI-Y)(up to visit 6, an average of 3 and a half months)
- Depression score assessed by the Montgomery-Asberg Depression Rating Scale (MADRS)(up to visit 6, an average of 3 and a half months)
- Subjective sleep quality assessed by the Pittsburgh Sleep Quality Index (PSQI)(up to visit 6, an average of 3 and a half months)
- Quality of life (SF-12 v2)(up to visit 6, an average of 3 and a half months)