Alcohol Use Disorders, Hepatitis C
Conditions
Brief summary
Hepatitis C (HCV) is the most common blood born virus in the United States, affecting 1.8% of the general population and more than 5% of Veterans using VA facilities. As Veterans with HCV have high rates of co-morbid alcohol use disorders that accelerate greatly the liver damage caused by HCV, a safe and effective treatment for alcohol use disorders is needed. Baclofen is a novel treatment for alcohol use disorders that has minimal effect on the liver and may represent a safe and efficacious treatment option for Veterans with HCV and co-morbid alcohol use disorders.
Detailed description
Project: Efficacy of baclofen in reducing alcohol consumption in Veterans with HCV Principal Investigator: Peter Hauser, MD Keywords: Hepatitis C, Substance-Related Disorders, Alcoholism Abstract PLAN/METHODS: Two sites of the national VA Hepatitis C Resource Center, including Minneapolis and Portland VA Medical Centers (VAMCs), the Long Beach VAMC, and the San Diego VAMC (total 4 sites) will recruit 180 men, women, and minority Veterans who are HCV positive and currently drinking alcohol. Participants will be assessed for current alcohol use and alcohol use disorders and enrolled in the study if they meet eligibility criteria, mainly that they are drinking more than 7 drinks a week or have one heavy drinking day a week for the preceding two weeks. Enrolled subjects will be randomly assigned to one of two groups: Experimental group (Baclofen) or control (placebo). Subjects will be followed for a total of 14 weeks, and follow-up data will be collected at a total of 11 visits (weeks 1,2,3,4,6,8,10,12, and 14). At each visit, interviews will be conducted by a blinded interviewer assessing current stage of change and current alcohol use along with any changes in mood and psychological or somatic symptoms. HCV viral titers will be obtained at baseline and again at week 12 to determine the effect of abstinence on this measure. Data will also be collected from participants' medical records regarding enrollment and attendance in substance abuse treatment or self-help programs (Alcoholics Anonymous). Data will be analyzed using repeated measure ANOVAs to compare the groups on alcohol use and stage of change. CLINICAL RELEVANCE: This study focuses on a current Veterans Health Administration (VHA) priority: treatment of Veterans with HCV. Alcohol use in this population is a major risk factor for progression of liver disease. The investigators anticipate that the Baclofen proposed in this study will result in reduced alcohol use, which is expected to result in a slowing of the progression of liver disease, improvement in physical health, and a reduction in long-term service utilization and mortality rates. POTENTIAL IMPACT ON VETERANS HEALTH CARE: Effectively addressing alcohol use disorders in a hepatitis clinic will contribute to a new standard of care for HCV patients within the VA. Co-located care for patients with comorbid medical and substance use disorders is likely to improve access to effective treatment, acceptance by patients and improve clinical efficiency.
Interventions
DRUGbaclofen
baclofen 10 mg tid
DRUGplacebo
placebo pill tid
Sponsors
VA Office of Research and Development
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Criteria for Participation Include if: * Male or female * Age 18 or older Medical record shows: * Serum antibody positive for HCV and PCR (Polymerase Chain Reaction) confirmation, Men or Women: \> 7 drinks per week for each of the proceeding 2 weeks Or One heavy drinking day per week for 2 weeks (Heavy drinking day: 5 drinks in one day for men and \>4 drinks in one day for women) based on Timeline Followback method (TLFB) * Alcohol use Disorder (abuse or dependence) based on Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders (SCID) * Yes Medical record and self report * Medical record, self report, SCID, Beck Depression Inventory -II (BDI-II) * Able to attend clinic appointments * Yes No Self-report
Exclusion criteria
Criteria for Participation Exclude if: * Male or female * Under age 18 * Cocaine, methamphetamine or opioid dependence within the past 6 months\* * Any known pre-existing medical conditions that could interfere with participation in the protocol, such as: * Central Nervous System (CNS) trauma * Known cognitive impairment * Dementia * Encephalopathy from liver disease * Acute psychiatric instability, such as significant psychosis, mania, or elevated risk for suicide * Not able to attend clinic appointments * Pregnant women * If any of the following medication are being used: * Ondansetron * Disulfiram * Topiramate * Naltrexone * Acamprosate * Buprenorphine * Methadone
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Drinking Days in the Past Two Weeks | 12 Weeks | — |
| Number of Drinks Consumed Per Two Week Segments | 12 weeks | — |
| Number of Heavy Drinking Days Per Two Week Segment | 12 weeks | A heavy drinking day was defined as ≥4 drinks/ day if female or ≥5 drinks/day if male |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Baclofen baclofen 10 mg po tid
baclofen: baclofen 10 mg tid | 88 |
| Placebo placebo given tid
placebo: placebo pill tid | 92 |
| Total | 180 |
Baseline characteristics
| Characteristic | Placebo | Total | Baclofen |
|---|---|---|---|
| Age, Continuous | 57.5 Years STANDARD_DEVIATION 6.9 | 56.6 Years STANDARD_DEVIATION 1.3 | 55.7 Years STANDARD_DEVIATION 7.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 12 Participants | 25 Participants | 13 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 76 Participants | 146 Participants | 70 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 4 Participants | 9 Participants | 5 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 35 Participants | 66 Participants | 31 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants | 7 Participants | 3 Participants |
| Race (NIH/OMB) White | 50 Participants | 102 Participants | 52 Participants |
| Sex: Female, Male Female | 0 Participants | 3 Participants | 3 Participants |
| Sex: Female, Male Male | 92 Participants | 177 Participants | 85 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 70 / 88 | 68 / 92 |
| serious Total, serious adverse events | 6 / 88 | 3 / 92 |
Outcome results
Primary
Number of Drinking Days in the Past Two Weeks
Time frame: 12 Weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Baclofen | Number of Drinking Days in the Past Two Weeks | Weeks 2-3 | 6.2 Number of Drinking Days/2 weeks | Standard Error 0.55 |
| Baclofen | Number of Drinking Days in the Past Two Weeks | Weeks 6-7 | 5.4 Number of Drinking Days/2 weeks | Standard Error 0.57 |
| Baclofen | Number of Drinking Days in the Past Two Weeks | Weeks 0-1 | 6.8 Number of Drinking Days/2 weeks | Standard Error 0.55 |
| Baclofen | Number of Drinking Days in the Past Two Weeks | Weeks 8-9 | 5.1 Number of Drinking Days/2 weeks | Standard Error 0.58 |
| Baclofen | Number of Drinking Days in the Past Two Weeks | Weeks 4-5 | 5.7 Number of Drinking Days/2 weeks | Standard Error 0.57 |
| Baclofen | Number of Drinking Days in the Past Two Weeks | Weeks 10-11 | 4.6 Number of Drinking Days/2 weeks | Standard Error 0.55 |
| Baclofen | Number of Drinking Days in the Past Two Weeks | Baseline | 8.6 Number of Drinking Days/2 weeks | Standard Error 0.5 |
| Placebo | Number of Drinking Days in the Past Two Weeks | Weeks 10-11 | 4.7 Number of Drinking Days/2 weeks | Standard Error 0.63 |
| Placebo | Number of Drinking Days in the Past Two Weeks | Baseline | 8.9 Number of Drinking Days/2 weeks | Standard Error 0.45 |
| Placebo | Number of Drinking Days in the Past Two Weeks | Weeks 0-1 | 7.1 Number of Drinking Days/2 weeks | Standard Error 0.54 |
| Placebo | Number of Drinking Days in the Past Two Weeks | Weeks 2-3 | 6.3 Number of Drinking Days/2 weeks | Standard Error 0.55 |
| Placebo | Number of Drinking Days in the Past Two Weeks | Weeks 4-5 | 5.8 Number of Drinking Days/2 weeks | Standard Error 0.58 |
| Placebo | Number of Drinking Days in the Past Two Weeks | Weeks 6-7 | 5.4 Number of Drinking Days/2 weeks | Standard Error 0.59 |
| Placebo | Number of Drinking Days in the Past Two Weeks | Weeks 8-9 | 4.8 Number of Drinking Days/2 weeks | Standard Error 0.59 |
Comparison: This was an intent to treat analysis where Generalized Estimating Equations, using the Negative Binomial function, were used to test for group, time, and group by time effects for drinks, drinking days, and heavy drinking days. This analysis assessed time effects for the number of drinking days.p-value: <0.01Wald Chi-squared
Comparison: This was an intent to treat analysis where Generalized Estimating Equations, using the Negative Binomial function, were used to test for group, time, and group by time effects for drinks, drinking days, and heavy drinking days. This analysis assessed group effects for the number of drinking days.p-value: >0.01Wald Chi-Squared
Comparison: This was an intent to treat analysis where Generalized Estimating Equations, using the Negative Binomial function, were used to test for group, time, and group by time effects for drinks, drinking days, and heavy drinking days. This analysis assessed time by group effects for the number of drinking days.p-value: >0.01Wald Chi-Squared
Primary
Number of Drinks Consumed Per Two Week Segments
Time frame: 12 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Baclofen | Number of Drinks Consumed Per Two Week Segments | Weeks 4-5 | 28.46 Number of Drinks/2 Weeks | Standard Error 3.62 |
| Baclofen | Number of Drinks Consumed Per Two Week Segments | Weeks 6-7 | 31.82 Number of Drinks/2 Weeks | Standard Error 5.54 |
| Baclofen | Number of Drinks Consumed Per Two Week Segments | Weeks 0-1 | 41.89 Number of Drinks/2 Weeks | Standard Error 4.42 |
| Baclofen | Number of Drinks Consumed Per Two Week Segments | Weeks 8-9 | 26.01 Number of Drinks/2 Weeks | Standard Error 4.59 |
| Baclofen | Number of Drinks Consumed Per Two Week Segments | Baseline | 60.09 Number of Drinks/2 Weeks | Standard Error 5.04 |
| Baclofen | Number of Drinks Consumed Per Two Week Segments | Weeks 10-11 | 18.82 Number of Drinks/2 Weeks | Standard Error 2.67 |
| Baclofen | Number of Drinks Consumed Per Two Week Segments | Weeks 2-3 | 33.88 Number of Drinks/2 Weeks | Standard Error 4.32 |
| Placebo | Number of Drinks Consumed Per Two Week Segments | Weeks 10-11 | 22.85 Number of Drinks/2 Weeks | Standard Error 3.71 |
| Placebo | Number of Drinks Consumed Per Two Week Segments | Baseline | 67.23 Number of Drinks/2 Weeks | Standard Error 5.09 |
| Placebo | Number of Drinks Consumed Per Two Week Segments | Weeks 0-1 | 47.68 Number of Drinks/2 Weeks | Standard Error 4.97 |
| Placebo | Number of Drinks Consumed Per Two Week Segments | Weeks 4-5 | 37.73 Number of Drinks/2 Weeks | Standard Error 5.65 |
| Placebo | Number of Drinks Consumed Per Two Week Segments | Weeks 6-7 | 30.73 Number of Drinks/2 Weeks | Standard Error 5.04 |
| Placebo | Number of Drinks Consumed Per Two Week Segments | Weeks 8-9 | 26.69 Number of Drinks/2 Weeks | Standard Error 4.36 |
| Placebo | Number of Drinks Consumed Per Two Week Segments | Weeks 2-3 | 39.07 Number of Drinks/2 Weeks | Standard Error 4.52 |
Comparison: This was an intent to treat analysis where Generalized Estimating Equations, using the Negative Binomial function, were used to test for group, time, and group by time effects for drinks, drinking days, and heavy drinking days. This analysis assessed time effects for the number of drinks.p-value: <0.01Wald Chi-Squared
Comparison: This was an intent to treat analysis where Generalized Estimating Equations, using the Negative Binomial function, were used to test for group, time, and group by time effects for drinks, drinking days, and heavy drinking days. This analysis assessed group effects for the number of drinks.p-value: >0.01Wald Chi-Squared
Comparison: This was an intent to treat analysis where Generalized Estimating Equations, using the Negative Binomial function, were used to test for group, time, and group by time effects for drinks, drinking days, and heavy drinking days. This analysis assessed group by time effects for the number of drinks.p-value: >0.01Wald Chi-Squared
Primary
Number of Heavy Drinking Days Per Two Week Segment
A heavy drinking day was defined as ≥4 drinks/ day if female or ≥5 drinks/day if male
Time frame: 12 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Baclofen | Number of Heavy Drinking Days Per Two Week Segment | Weeks 2-3 | 2.59 Number of heavy drinking days/2 weeks | Standard Error 0.37 |
| Baclofen | Number of Heavy Drinking Days Per Two Week Segment | Weeks 6-7 | 2.52 Number of heavy drinking days/2 weeks | Standard Error 0.46 |
| Baclofen | Number of Heavy Drinking Days Per Two Week Segment | Weeks 0-1 | 3.67 Number of heavy drinking days/2 weeks | Standard Error 0.46 |
| Baclofen | Number of Heavy Drinking Days Per Two Week Segment | Weeks 8-9 | 2.10 Number of heavy drinking days/2 weeks | Standard Error 0.46 |
| Baclofen | Number of Heavy Drinking Days Per Two Week Segment | Weeks 4-5 | 2.40 Number of heavy drinking days/2 weeks | Standard Error 0.38 |
| Baclofen | Number of Heavy Drinking Days Per Two Week Segment | Weeks 10-11 | 1.37 Number of heavy drinking days/2 weeks | Standard Error 0.31 |
| Baclofen | Number of Heavy Drinking Days Per Two Week Segment | Baseline | 6.48 Number of heavy drinking days/2 weeks | Standard Error 0.53 |
| Placebo | Number of Heavy Drinking Days Per Two Week Segment | Weeks 10-11 | 2.15 Number of heavy drinking days/2 weeks | Standard Error 0.46 |
| Placebo | Number of Heavy Drinking Days Per Two Week Segment | Baseline | 7.18 Number of heavy drinking days/2 weeks | Standard Error 0.51 |
| Placebo | Number of Heavy Drinking Days Per Two Week Segment | Weeks 0-1 | 4.04 Number of heavy drinking days/2 weeks | Standard Error 0.46 |
| Placebo | Number of Heavy Drinking Days Per Two Week Segment | Weeks 2-3 | 3.07 Number of heavy drinking days/2 weeks | Standard Error 0.41 |
| Placebo | Number of Heavy Drinking Days Per Two Week Segment | Weeks 4-5 | 3.29 Number of heavy drinking days/2 weeks | Standard Error 0.5 |
| Placebo | Number of Heavy Drinking Days Per Two Week Segment | Weeks 6-7 | 2.44 Number of heavy drinking days/2 weeks | Standard Error 0.44 |
| Placebo | Number of Heavy Drinking Days Per Two Week Segment | Weeks 8-9 | 2.18 Number of heavy drinking days/2 weeks | Standard Error 0.42 |
Comparison: This was an intent to treat analysis where Generalized Estimating Equations, using the Negative Binomial function, were used to test for group, time, and group by time effects for drinks, drinking days, and heavy drinking days. This analysis assessed time effects for the number of heavy drinking days.p-value: <0.01Wald Chi-Squared
Comparison: This was an intent to treat analysis where Generalized Estimating Equations, using the Negative Binomial function, were used to test for group, time, and group by time effects for drinks, drinking days, and heavy drinking days. This analysis assessed group effects for the number of heavy drinking days.p-value: >0.01Wald Chi-Squared
Comparison: This was an intent to treat analysis where Generalized Estimating Equations, using the Negative Binomial function, were used to test for group, time, and group by time effects for drinks, drinking days, and heavy drinking days. This analysis assessed group by time effects for the number of heavy drinking days.p-value: >0.01Wald Chi-Squared