Baclofen for Improving Benzodiazepine Titration in Benzodiazepine Dependence

NCT ID: NCT05935553

Last Updated: 2026-01-30

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 93 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2026-01-15
• Study Completion Date: 2028-10-30

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Baclofen 30 microgram (mg) treatment

baclofen treatment (30 mg/per day)

Group Type: EXPERIMENTAL

Baclofen 30 mg

Intervention Type: 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 60 mg

baclofen treatment (60 mg/per day)

Group Type: EXPERIMENTAL

Baclofen 60 mg

Intervention Type: 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

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: 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

Interventions

Baclofen 30 mg

• 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

Intervention Type: DRUG

Baclofen 60 mg

• 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

Intervention Type: DRUG

Placebo

• 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

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hospices Civils de Lyon

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Centre Hospitalier le Vinatier

Bron, , France

Site Status: NOT_YET_RECRUITING

Hôpital Edouard Herriot

Lyon, , France

Site Status: RECRUITING

Countries

France

Central Contacts

Benjamin ROLLAND, PU, PH

Role: CONTACT

Benjamin.rolland@chu-lyon.fr

04 37 91 50 72 ext. +33

Sonia Galletti

Role: CONTACT

Sonia.galletti@chu-lyon.fr

04 27 85 77 39 ext. +33

Facility Contacts

Christophe ICARD, MD, PhD

Role: primary

christophe.icard@ch-le-vinatier.fr

04 37 91 50 75 ext. +33

Benjamin ROLLAND, PU, PH

Role: primary

Benjamin.rolland@chu-lyon.fr

04 37 91 50 72 ext. +33

Sonia Galletti

Role: backup

Sonia.galletti@chu-lyon.fr

04 27 85 77 39 ext. +33

Other Identifiers

2022-502307-30-00

Identifier Type: CTIS

Identifier Source: secondary_id

69HCL21_1318

Identifier Type: -

Identifier Source: org_study_id