Alcohol Use Disorder
Conditions
Brief summary
AUDs are difficult to treat, and relapse rates are high, with an estimated 80% of individuals with AUDs returning to alcohol use after completing addictions treatment. Novel treatment approaches are needed to enhance long term sobriety. The investigator's research team has been investigating the use of acamprosate to prevent relapse to alcohol use. Unfortunately despite being FDA approved and endorsed by the American Psychiatric Association only 10% of patients treated for AUD are prescribed acamprosate or other antidipsotropic medications. The number is higher for patients treated in programs affiliated with Mayo Clinic Addiction Services (approximately 20%) but is way less than expected. The most common reasons behind these low numbers are the understanding that not every patient benefits from the use of specific medication and the lack of biomarkers predictive of response. The purpose of this project is to identify such biomarkers by discovery of genomic and metabolomic markers associated with response to acamprosate treatment.
Interventions
DRUGAcamprosate
The research pharmacy contracted for this study will randomize the study participants for all sites with placebo or acamprosate.
OTHERPlacebo
The research pharmacy contracted for this study will randomize the study participants for all sites with placebo or acamprosate.
Sponsors
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Mayo Clinic
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
1. Age 18 to85; DSM-5 diagnosis of AUD determined by PRISM; 2. Completion of alcohol detoxification (CIWA score \< 5) and no alcohol for at least 7 days (but no more than 35 days); 3. Ability to provide informed consent 4. Ability to speak English 5. Willingness to use the study medications for 3 months and attend follow-up visits. 6. No chronic/daily use of benzodiazepines, opioids, or stimulants for a period of time which is determined by 3 x the medication half-life value (see addendum A) to be completed before the initiation of study medication (acamprosate or placebo). 7. Willingness to discontinue previously prescribed acamprosate for a period of at least 3 days before randomization to study medication (acamprosate or placebo).
Exclusion criteria
1. Hypersensitivity or allergy to acamprosate 2. Current use of wellbutrin and not willing to switch to an acceptable antidepressant medication 3. Renal impairment (creatinine level \>1.5 mg/dL); 4. Diagnosis of advanced liver disease indicated in the medical record or by a MELD score of above 10; 5. Women who are pregnant, breastfeeding, or planning to become pregnant during the next year; 6. Primary diagnosis of substance use disorder other than alcohol as determined by PRISM or in medical record review or secondary diagnosis of active (within the past year) benzo/sedative dependence, opioid dependence, stimulant dependence, heroin dependence, and/or cocaine dependence 7. Refusal to abstain from any chronic/daily use of prescribed benzodiazepines, opioids, stimulants, cannabis related medication such as CBD or medical marijuana, during the course of participation. 8. Current use of Naltrexone and not willing to stop and switch to Acamprosate/Placebo 9. Current use of Antabuse. 10. Active suicidal ideation or any unstable medical or psychiatric condition as determined by responses to PRISM or by the investigator. 11. Status of involuntary or court-ordered admission at time of consent.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Continuous Sobriety According to Alcohol Timeline Follow Back | Will be defined as continuous sobriety (yes/no) during 3 months of treatment | The Alcohol Timeline Follow Back (TLFB) is a drinking assessment method that obtains estimates of daily drinking and has been evaluated with clinical and nonclinical populations. Using a calendar, people provide retrospective estimates of their daily drinking over a specified time period that can vary up to 12 months from the interview date. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Day Until First Alcohol Use (Relapse) - Alcohol Timeline Follow Back | The number of days until first alcohol use (relapse) assessed by TLFB during 3 months of treatment | The Alcohol Timeline Follow Back (TLFB) is a drinking assessment method that obtains estimates of daily drinking and has been evaluated with clinical and nonclinical populations. Using a calendar, people provide retrospective estimates of their daily drinking over a specified time period that can vary up to 12 months from the interview date. |
| Days Until First Relapse (Heavy Relapse) - Timeline Follow Back | Number of days until first relapse (heavy relapse) between medication start and 3 months follow-up | The Alcohol Timeline Follow Back (TLFB) is a drinking assessment method that obtains estimates of daily drinking and has been evaluated with clinical and nonclinical populations. Using a calendar, people provide retrospective estimates of their daily drinking over a specified time period that can vary up to 12 months from the interview date. |
| Cumulative Abstinence Duration - Timeline Follow Back | Cumulative abstinence duration proportion: proportion of days over the length of 3 month follow-up during which participants were abstinent from alcohol use, a score range of 0 (drinking continuously) to 100 (maintain complete abstinence) is applied. | The Alcohol Timeline Follow Back (TLFB) is a drinking assessment method that obtains estimates of daily drinking and has been evaluated with clinical and nonclinical populations. Using a calendar, people provide retrospective estimates of their daily drinking over a specified time period that can vary up to 12 months from the interview date. |
Countries
United States
Participant flow
Recruitment details
Recruitment for the study began in June of 2019 and continued to July 2023 with follow-up visits completed in October 2023. All participants were recruited while attending a residential intensive treatment program.
Pre-assignment details
Participants were evaluated by PRISM to confirm alcohol use disorder diagnosis and no secondary diagnosis of active other substance use disorder was present. Additional testing was done for renal impairment and advanced liver disease. Participants were required to be willing to stop chronic/daily use of prescribed benzodiazepines, opioids, stimulants, cannabis related medication such as CBD or medical marijuana during participation. Review of medications including anti-depressants was done.
Participants by arm
| Arm | Count |
|---|---|
| Acamprosate All participants will be randomized to receive acamprosate or placebo in a double-blinded placebo-controlled trial.
The most common side effect associated with acamprosate use is diarrhea, which occurs in approximately 16% of patients. Other frequently occurring side effects include asthenia, nausea, pruritus, and flatulence, headache, abdominal pain, flu syndrome, edema, weight gain, and myalgia.
Acamprosate: The research pharmacy contracted for this study will randomize the study participants for all sites with placebo or acamprosate. | 184 |
| Placebo All participants will be randomized to receive acamprosate or placebo in a double-blinded placebo-controlled trial.
Placebo: The research pharmacy contracted for this study will randomize the study participants for all sites with placebo or acamprosate. | 104 |
| Total | 288 |
Baseline characteristics
| Characteristic | Acamprosate | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 8 Participants | 0 Participants | 8 Participants |
| Age, Categorical Between 18 and 65 years | 176 Participants | 104 Participants | 280 Participants |
| Age, Continuous | 45.986 Years STANDARD_DEVIATION 11.761 | 44.023 Years STANDARD_DEVIATION 11.071 | 45.277 Years STANDARD_DEVIATION 11.536 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 2 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 168 Participants | 96 Participants | 264 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 16 Participants | 6 Participants | 22 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 2 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 16 Participants | 6 Participants | 22 Participants |
| Race (NIH/OMB) White | 161 Participants | 95 Participants | 256 Participants |
| Sex: Female, Male Female | 55 Participants | 30 Participants | 85 Participants |
| Sex: Female, Male Male | 129 Participants | 74 Participants | 203 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 184 | 0 / 104 |
| other Total, other adverse events | 55 / 184 | 35 / 104 |
| serious Total, serious adverse events | 0 / 184 | 0 / 104 |
Outcome results
Primary
Number of Participants With Continuous Sobriety According to Alcohol Timeline Follow Back
The Alcohol Timeline Follow Back (TLFB) is a drinking assessment method that obtains estimates of daily drinking and has been evaluated with clinical and nonclinical populations. Using a calendar, people provide retrospective estimates of their daily drinking over a specified time period that can vary up to 12 months from the interview date.
Time frame: Will be defined as continuous sobriety (yes/no) during 3 months of treatment
Population: The analyzed sample included participants that completed 3 months of the study, as well as, those that dropped out but were known to have relapsed before 3 months.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Acamprosate | Number of Participants With Continuous Sobriety According to Alcohol Timeline Follow Back | 66 Participants |
| Placebo | Number of Participants With Continuous Sobriety According to Alcohol Timeline Follow Back | 39 Participants |
Secondary
Cumulative Abstinence Duration - Timeline Follow Back
The Alcohol Timeline Follow Back (TLFB) is a drinking assessment method that obtains estimates of daily drinking and has been evaluated with clinical and nonclinical populations. Using a calendar, people provide retrospective estimates of their daily drinking over a specified time period that can vary up to 12 months from the interview date.
Time frame: Cumulative abstinence duration proportion: proportion of days over the length of 3 month follow-up during which participants were abstinent from alcohol use, a score range of 0 (drinking continuously) to 100 (maintain complete abstinence) is applied.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Acamprosate | Cumulative Abstinence Duration - Timeline Follow Back | 96.57 percentage of days | Standard Deviation 6.85 |
| Placebo | Cumulative Abstinence Duration - Timeline Follow Back | 96.01 percentage of days | Standard Deviation 13.9 |
Secondary
Days Until First Relapse (Heavy Relapse) - Timeline Follow Back
The Alcohol Timeline Follow Back (TLFB) is a drinking assessment method that obtains estimates of daily drinking and has been evaluated with clinical and nonclinical populations. Using a calendar, people provide retrospective estimates of their daily drinking over a specified time period that can vary up to 12 months from the interview date.
Time frame: Number of days until first relapse (heavy relapse) between medication start and 3 months follow-up
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Acamprosate | Days Until First Relapse (Heavy Relapse) - Timeline Follow Back | 81 Number of days |
| Placebo | Days Until First Relapse (Heavy Relapse) - Timeline Follow Back | 82.5 Number of days |
Secondary
Day Until First Alcohol Use (Relapse) - Alcohol Timeline Follow Back
The Alcohol Timeline Follow Back (TLFB) is a drinking assessment method that obtains estimates of daily drinking and has been evaluated with clinical and nonclinical populations. Using a calendar, people provide retrospective estimates of their daily drinking over a specified time period that can vary up to 12 months from the interview date.
Time frame: The number of days until first alcohol use (relapse) assessed by TLFB during 3 months of treatment
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Acamprosate | Day Until First Alcohol Use (Relapse) - Alcohol Timeline Follow Back | 80 Number of days |
| Placebo | Day Until First Alcohol Use (Relapse) - Alcohol Timeline Follow Back | 82 Number of days |