Efficacy and Safety of High Dose Baclofen for Alcohol Dependence
The proposed study will carefully test the hypothesis that a robust dose of baclofen (90 mg/day) has efficacy and is safe in individuals with alcohol dependence. Furthermore, the proposal will test whether an indicator of physical dependence, i.e. drinks/drinking day, predicts response to baclofen. Additionally, the proposal will examine the anti-anxiety effects of baclofen within an alcohol dependent population and ascertain whether baseline levels of anxiety predict response to baclofen.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Efficacy and Safety of High Dose Baclofen for Alcohol Dependence|
- Mean % Heavy Drinking Days [ Time Frame: Every 1-2 weeks up to 107 days of active trial ] [ Designated as safety issue: No ]
- Mean % Abstinent Drinking Days [ Time Frame: Every 1-2 weeks up to 107 days of active trial ] [ Designated as safety issue: No ]
- Anxiety level based on Spielberger Scale for State Anxiety [ Time Frame: Every 1-2 weeks up to 107 days of active trial ] [ Designated as safety issue: No ]
- Self-reported sedation. [ Time Frame: Every 1-2 weeks up to 107 days of active trial ] [ Designated as safety issue: Yes ]
|Study Start Date:||November 2013|
|Estimated Study Completion Date:||October 2017|
|Estimated Primary Completion Date:||October 2017 (Final data collection date for primary outcome measure)|
Placebo Comparator: Placebo
Participants will take placebo for 107 days, 3 times per day. Placebo will be given in blister packs.
Pill containing no pharmacologically active substance.
Other Name: Sugar pill
Active Comparator: 30 Mg Baclofen
Participants will take baclofen/placebo for 107 days, 3 times per day. Baclofen will be given in blister packs. The 30 mg/d arm will reach 30 mg/d at day 3 and titrate down starting at day 101.
Baclofen is a GABA-B agonist
Other Name: Lioresol
Active Comparator: 90 mg Baclofen
Participants will take baclofen/placebo for 107 days, 3 times per day. Baclofen will be given in blister packs. The 90 mg/d arm will reach 90 mg/d at day 12 and titrate down starting at day 101.
Baclofen is a GABA-B agonist
Other Name: Lioresol
Alcohol dependence (AD) is a common problem with significant health consequences. Treatment of AD is evolving to include both counseling methods and medications. Several medications have been discovered, that show efficacy in AD, e.g. naltrexone, acamprosate. However, the overall effect of existing medications is modest leaving a clear need for the development of new pharmacotherapies. The gamma-aminobutyric acid (GABA)-B receptor agonist baclofen has attracted attention as a potential new medication for AD based on preclinical data and early clinical trials. Baclofen is an FDA approved medication with an excellent safety profile even for patients with liver cirrhosis—a not uncommon consequence of AD. Questions have arisen with regards to the efficacy of baclofen and whether higher doses of baclofen are safe and more effective than the prior tested dose of 30 mg/ day. There is emerging evidence that severity of dependence is positively associated with baclofen response. The main goal of the present proposal is to test the efficacy and safety of 30 mg/d and 90 mg/d of baclofen compared to placebo controlling for severity of dependence as assessed by drinks/drinking day. A primary secondary goal will examine for an anxiolytic effect of baclofen. The study proposes to enroll 120 men and women with AD in a randomized, placebo-controlled trial to include at least 60 individuals with more severe AD (≥14 drinks/drinking day for men; ≥10 drinks/drinking day for women) with randomization to baclofen or placebo balanced for this variable. Baclofen will be titrated to 10 mg t.i.d over 3 days and to 30 mg t.i.d over 12 days and maintained at that level for 12 weeks and then downtitrated for a total study time of 16 weeks. Medical Management will be provided to encourage progress towards drinking goals and to enhance retention and compliance. Drinking patterns, anxiety levels, sleep patterns, craving for alcohol, gamma-glutamyl transferase (GGT) and carbohydrate deficient transferring (CDT) will be assessed. Trough blood levels of R & S-baclofen will be assessed in all individuals at week 4.
In summary, the present proposal is innovative and of clinical significance as it will test and compare standard and high-dose baclofen for efficacy and safety in individuals with AD. The proposal is adequately powered to test the primary hypothesis and provides good power to assess whether drinks/drinking day is predictive of baclofen response. Adequate power is also present to examine the anxiolytic effect of baclofen. Ascertaining the effects of standard and high-dose baclofen, the predictive value of heavy drinking on baclofen response and the anxiolytic effect of baclofen are important goals towards determining whether baclofen has true value for the clinical management of the patient with alcohol dependence.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01980706
|Contact: Melissa D Stansbury, BSfirstname.lastname@example.org|
|Contact: James C Garbutt, MDemail@example.com|
|United States, North Carolina|
|University of North Carolina at Chapel Hill||Recruiting|
|Chapel Hill, North Carolina, United States, 27599|
|Contact: Melissa Stansbury 919-966-0011 firstname.lastname@example.org|
|Principal Investigator: James C Garbutt, MD|
|Principal Investigator:||James C Garbutt, MD||University of North Carolina|