Efficacy and Safety of High Dose Baclofen for Alcohol Dependence
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|ClinicalTrials.gov Identifier: NCT01980706|
Recruitment Status : Completed
First Posted : November 11, 2013
Results First Posted : January 8, 2019
Last Update Posted : June 12, 2019
|Condition or disease||Intervention/treatment||Phase|
|Alcoholism||Drug: Baclofen Drug: Placebo||Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||120 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||Efficacy and Safety of High Dose Baclofen for Alcohol Dependence|
|Actual Study Start Date :||December 12, 2013|
|Actual Primary Completion Date :||October 26, 2017|
|Actual Study Completion Date :||October 26, 2017|
Placebo Comparator: Placebo
Participants will take placebo for 16 weeks, 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 16 weeks, 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: Lioresal
Active Comparator: 90 mg Baclofen
Participants will take baclofen/placebo for 16 weeks, 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 95.
Baclofen is a GABA-B agonist
Other Name: Lioresal
- Mean Percentage of Heavy Drinking Days [ Time Frame: Every 1-2 weeks up to 16 weeks of active trial ]The frequency of heavy drinking days (5 or more drinks for a man and 4 or more drinks for a woman) as percentage during the treatment phase.
- Mean Percentage of Abstinent Drinking Days [ Time Frame: Every 1-2 weeks up to 16 weeks of active trial ]Percent of abstinent days over the course of the trial.
- Mean Spielberger State-Trait Anxiety Inventory Score [State] [ Time Frame: Every 1-2 weeks up to 16 weeks of active trial ]The Spielberger State and Trait Anxiety Inventory (STAI) is a validated self-reporting instrument used to assess anxiety in adults.The inventory consists of state anxiety, which evaluates how the subject feels currently (transient anxiety). The State scale consists of 20 questions, each question rated 1-4, and a higher score indicates greater anxiety. Total score ranges from 20 (no anxiety) to 80 (maximum anxiety). The scores are averaged over the trial.
- Mean Penn Alcohol Craving Scale Score [ Time Frame: Every 1-2 weeks up to 16 weeks of active trial ]Penn Alcohol Craving Scale (PACS) is a five-item self administered instrument for assessing craving, frequency, intensity, and duration of thoughts about drinking as well as the ability to resist drinking. Scores range from a minimum of zero to a maximum of 30. Lower scores are associated with lower level of craving for alcohol. Scores are averaged over the trial.
- Carbohydrate-deficient Transferrin [ Time Frame: End of trial, generally 16 weeks ]Lab test assessing history of heavy drinking with greater specificity than GGT. Higher levels are indicative of greater levels of drinking.
- Self-reported Sedation on at Least One Occasion by a Participant [ Time Frame: Every 1-2 weeks up to 16 weeks of active trial ]Any reporting of feeling sedated/sleepy/drowsy
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01980706
|United States, North Carolina|
|University of North Carolina at Chapel Hill|
|Chapel Hill, North Carolina, United States, 27599|
|Principal Investigator:||James C Garbutt, MD||University of North Carolina|