Clinical trial NCT05935553: Baclofen for Improving Benzodiazepine Titration in Benzodiazepine Dependence
Official title: Baclofen for Improving Benzodiazepine Titration in Benzodiazepine Dependence
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
PHASE3
Conditions: Benzodiazepine Dependence
Keywords: Benzodiazepine Dependence
baclofen
efficacy
Lead sponsor: Hospices Civils de Lyon
Sponsor class: OTHER
First posted: 2023-07-07
Enrollment: 93
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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).


Eligibility criteria: Inclusion Criteria:

* 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 50 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.

Exclusion Criteria:

* 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

Primary outcomes:
measure: Difference in total benzodiazepine consumption, in mg-diazepam
timeFrame: between the 28 days before inclusion in the clinical trial and the last 28 days of the clinical trial
Secondary outcomes:
measure: Frequency of serious adverse events of special interest
timeFrame: through study completion, an average of 4 and a half months
measure: Frequency of non-serious adverse events of special interest
timeFrame: through study completion, an average of 4 and a half months
measure: frequency of all-cause study discontinuations
timeFrame: through study completion, an average of 4 and a half months
measure: Frequency of benzodiazepine discontinuation at the last visit of the treatment period by urine test
timeFrame: at study completion, an average of 4 and a half months
measure: Frequency of benzodiazepine discontinuation at the last visit of the treatment period by B-TLFB questionnaire
timeFrame: at study completion, an average of 4 and a half months
measure: Frequency of benzodiazepine discontinuation at the last visit of the treatment period by the Clinical Institute Withdrawal Assessment of Benzodiazepine (CIWA-B) questionnaire
timeFrame: up to visit 6, an average of 3 and a half months
measure: Craving score assessed by the Visual Analog Scale (VAS)
timeFrame: up to visit 6, an average of 3 and a half months
measure: Anxiety symptoms assessed by the State Trait Inventory Anxiety (STAI-Y)
timeFrame: up to visit 6, an average of 3 and a half months
measure: Depression score assessed by the Montgomery-Asberg Depression Rating Scale (MADRS)
timeFrame: up to visit 6, an average of 3 and a half months
measure: Subjective sleep quality assessed by the Pittsburgh Sleep Quality Index (PSQI)
timeFrame: up to visit 6, an average of 3 and a half months
measure: Quality of life (SF-12 v2)
timeFrame: up to visit 6, an average of 3 and a half months
Other outcomes:
Locations:
city: Bron
country: France
facility: Centre Hospitalier le Vinatier
city: Lyon
country: France
facility: Hôpital Edouard Herriot
Study officials:
References: