Baclofen for Improving Benzodiazepine Titration in Benzodiazepine Dependence

NCT05935553 | Recruiting Phase 2

• 2 other identifiers: 69HCL21_13182022-502307-30-00
• Study Type: interventional
• Target: 93
• Locations: 1 country
• Sites: 2

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).

Conditions

Benzodiazepine Dependence

Keywords

Benzodiazepine Dependence; baclofen; efficacy

Outcome Measures

Primary Outcomes (1)

• Difference in total benzodiazepine consumption, in mg-diazepam

  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).

  between the 28 days before inclusion in the clinical trial and the last 28 days of the clinical trial

Secondary Outcomes (11)

• 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 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 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

Study Arms (3)

Baclofen 30 microgram (mg) treatment

EXPERIMENTAL

baclofen treatment (30 mg/per day)

Drug: Baclofen 30 mg

Baclofen 60 mg

EXPERIMENTAL

baclofen treatment (60 mg/per day)

Drug: Baclofen 60 mg

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Baclofen 30 mg DRUG

* baclofen 10 mg capsule (for the 30 mg-baclofen 30 mg arm) * Dosage: 3 capsules of baclofen 10 mg per day * route of administration: Oral * duration of treatment: Total duration of treatment is 13 weeks including 1 week of dose escalation, 11 weeks of maintenance at full dose, and 1 week of dose de-escalation

Baclofen 30 microgram (mg) treatment

Baclofen 60 mg DRUG

* baclofen 20 mg capsule (for the 60 mg baclofen arm) * Dosage: 3 capsules of baclofen 20 mg per day * route of administration: Oral * duration of treatment: Total duration of treatment is 13 weeks including 1 week of dose escalation, 11 weeks of maintenance at full dose, and 1 week of dose de-escalation

Baclofen 60 mg

Placebo DRUG

* placebo capsule (for the placebo arm) * Dosage:3 capsules of placebo per day * route of administration: Oral * duration of treatment: Total duration of treatment is 13 weeks including 1 week of dose escalation, 11 weeks of maintenance at full dose, and 1 week of dose de-escalation

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients aged ≥ 18 years to ≤ 65 years
• For women of childbearing potential :
• 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
• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Hospices Civils de Lyon: lead

Study Sites (2)

Centre Hospitalier le Vinatier

Bron, 69500, France

NOT YET RECRUITING

Hôpital Edouard Herriot

Lyon, 69003, France

RECRUITING

MeSH Terms

Interventions

Baclofen

Intervention Hierarchy (Ancestors)

gamma-Aminobutyric Acid; Aminobutyrates; Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals

Central Study Contacts

Benjamin ROLLAND, PU, PH

CONTACT

04 37 91 50 72; Benjamin.rolland@chu-lyon.fr

Sonia Galletti

CONTACT

04 27 85 77 39; Sonia.galletti@chu-lyon.fr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 29, 2023
• First Posted: July 7, 2023
• Study Start: January 15, 2026
• Primary Completion (Estimated): October 30, 2028
• Study Completion (Estimated): October 30, 2028
• Last Updated: January 30, 2026

Record last verified: 2026-01

Locations

FR (2)