Trial Outcomes & Findings for Pharmacogenomics and Pharmacometabolomics of Acamprosate Treatment Outcome (NCT NCT03818191)

Last Updated: 2024-12-17

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

288 participants

Primary outcome timeframe

Will be defined as continuous sobriety (yes/no) during 3 months of treatment

Results posted on

2024-12-17

Participant Flow

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.

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.

Participant milestones

Participant milestones
Measure	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.	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.
Overall Study STARTED	184	104
Overall Study COMPLETED	81	51
Overall Study NOT COMPLETED	103	53

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Pharmacogenomics and Pharmacometabolomics of Acamprosate Treatment Outcome

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Acamprosate n=184 Participants 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.	Placebo n=104 Participants 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.	Total n=288 Participants Total of all reporting groups
Sex: Female, Male Female	55 Participants n=5 Participants	30 Participants n=7 Participants	85 Participants n=5 Participants
Sex: Female, Male Male	129 Participants n=5 Participants	74 Participants n=7 Participants	203 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	168 Participants n=5 Participants	96 Participants n=7 Participants	264 Participants n=5 Participants
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	176 Participants n=5 Participants	104 Participants n=7 Participants	280 Participants n=5 Participants
Age, Categorical >=65 years	8 Participants n=5 Participants	0 Participants n=7 Participants	8 Participants n=5 Participants
Age, Continuous	45.986 Years STANDARD_DEVIATION 11.761 • n=5 Participants	44.023 Years STANDARD_DEVIATION 11.071 • n=7 Participants	45.277 Years STANDARD_DEVIATION 11.536 • n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	16 Participants n=5 Participants	6 Participants n=7 Participants	22 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) White	161 Participants n=5 Participants	95 Participants n=7 Participants	256 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	16 Participants n=5 Participants	6 Participants n=7 Participants	22 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Acamprosate n=101 Participants 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.	Placebo n=55 Participants 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.
Number of Participants With Continuous Sobriety According to Alcohol Timeline Follow Back	66 Participants	39 Participants

SECONDARY outcome

Timeframe: The number of days until first alcohol use (relapse) assessed by TLFB during 3 months of treatment

Outcome measures

Outcome measures
Measure	Acamprosate n=127 Participants 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.	Placebo n=70 Participants 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.
Day Until First Alcohol Use (Relapse) - Alcohol Timeline Follow Back	80 Number of days Interval 31.5 to 89.0	82 Number of days Interval 43.0 to 89.0

SECONDARY outcome

Timeframe: Number of days until first relapse (heavy relapse) between medication start and 3 months follow-up

Outcome measures

Outcome measures
Measure	Acamprosate n=127 Participants 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.	Placebo n=70 Participants 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.
Days Until First Relapse (Heavy Relapse) - Timeline Follow Back	81 Number of days Interval 33.0 to 89.0	82.5 Number of days Interval 52.25 to 89.0

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Acamprosate n=101 Participants 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.	Placebo n=54 Participants 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.
Cumulative Abstinence Duration - Timeline Follow Back	96.57 percentage of days Standard Deviation 6.85	96.01 percentage of days Standard Deviation 13.90

Adverse Events

Acamprosate

Serious events: 0 serious events

Other events: 55 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 35 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Victor Karpyak, MD, PhD

Mayo Clinic

Phone: (507)284-8891

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Acamprosate n=184 participants at risk 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.	Placebo n=104 participants at risk 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.
Psychiatric disorders ER/Hospital visit for suicidal ideation, intoxication, or alcohol withdrawal	3.8% 7/184 • Number of events 8 • Adverse event data was collected up to 3 months during each patient's participation.	2.9% 3/104 • Number of events 3 • Adverse event data was collected up to 3 months during each patient's participation.
Reproductive system and breast disorders Loss of sexual interest or problems with erection or achieving orgasm	2.2% 4/184 • Number of events 4 • Adverse event data was collected up to 3 months during each patient's participation.	2.9% 3/104 • Number of events 3 • Adverse event data was collected up to 3 months during each patient's participation.
Cardiac disorders Prolonged QT interval	0.00% 0/184 • Adverse event data was collected up to 3 months during each patient's participation.	0.96% 1/104 • Number of events 1 • Adverse event data was collected up to 3 months during each patient's participation.
Nervous system disorders Headache/Migraine	2.7% 5/184 • Number of events 5 • Adverse event data was collected up to 3 months during each patient's participation.	1.9% 2/104 • Number of events 2 • Adverse event data was collected up to 3 months during each patient's participation.
Respiratory, thoracic and mediastinal disorders Cold/Flu	2.2% 4/184 • Number of events 5 • Adverse event data was collected up to 3 months during each patient's participation.	2.9% 3/104 • Number of events 5 • Adverse event data was collected up to 3 months during each patient's participation.
General disorders Jaw and Ear Pain, Broken Jaw	0.54% 1/184 • Number of events 1 • Adverse event data was collected up to 3 months during each patient's participation.	0.96% 1/104 • Number of events 1 • Adverse event data was collected up to 3 months during each patient's participation.
Nervous system disorders Difficulty Sleeping	3.3% 6/184 • Number of events 6 • Adverse event data was collected up to 3 months during each patient's participation.	3.8% 4/104 • Number of events 4 • Adverse event data was collected up to 3 months during each patient's participation.
Nervous system disorders Fatigue	0.54% 1/184 • Number of events 1 • Adverse event data was collected up to 3 months during each patient's participation.	3.8% 4/104 • Number of events 4 • Adverse event data was collected up to 3 months during each patient's participation.
Respiratory, thoracic and mediastinal disorders Shortness of Breath	0.54% 1/184 • Number of events 1 • Adverse event data was collected up to 3 months during each patient's participation.	0.00% 0/104 • Adverse event data was collected up to 3 months during each patient's participation.
Metabolism and nutrition disorders Increased Appetite	0.54% 1/184 • Number of events 1 • Adverse event data was collected up to 3 months during each patient's participation.	0.00% 0/104 • Adverse event data was collected up to 3 months during each patient's participation.
Nervous system disorders Seizure - no loss of consciousness	0.00% 0/184 • Adverse event data was collected up to 3 months during each patient's participation.	0.96% 1/104 • Number of events 1 • Adverse event data was collected up to 3 months during each patient's participation.
Musculoskeletal and connective tissue disorders Restless legs	0.54% 1/184 • Number of events 1 • Adverse event data was collected up to 3 months during each patient's participation.	0.00% 0/104 • Adverse event data was collected up to 3 months during each patient's participation.
Psychiatric disorders Side effects of Lexapro	0.54% 1/184 • Number of events 1 • Adverse event data was collected up to 3 months during each patient's participation.	0.00% 0/104 • Adverse event data was collected up to 3 months during each patient's participation.
Nervous system disorders Sciatica	0.00% 0/184 • Adverse event data was collected up to 3 months during each patient's participation.	0.96% 1/104 • Number of events 1 • Adverse event data was collected up to 3 months during each patient's participation.
Social circumstances Assault	0.00% 0/184 • Adverse event data was collected up to 3 months during each patient's participation.	0.96% 1/104 • Number of events 1 • Adverse event data was collected up to 3 months during each patient's participation.
Gastrointestinal disorders GI virus, upset, Diarrhea, gas	5.4% 10/184 • Number of events 11 • Adverse event data was collected up to 3 months during each patient's participation.	3.8% 4/104 • Number of events 4 • Adverse event data was collected up to 3 months during each patient's participation.
Musculoskeletal and connective tissue disorders Smashed Finger	0.54% 1/184 • Number of events 1 • Adverse event data was collected up to 3 months during each patient's participation.	0.00% 0/104 • Adverse event data was collected up to 3 months during each patient's participation.
Musculoskeletal and connective tissue disorders Muscle pain/feeling achy	3.8% 7/184 • Number of events 7 • Adverse event data was collected up to 3 months during each patient's participation.	1.9% 2/104 • Number of events 2 • Adverse event data was collected up to 3 months during each patient's participation.
Skin and subcutaneous tissue disorders Skin Peeling	0.54% 1/184 • Number of events 1 • Adverse event data was collected up to 3 months during each patient's participation.	0.00% 0/104 • Adverse event data was collected up to 3 months during each patient's participation.
Psychiatric disorders Anxiety	1.1% 2/184 • Number of events 2 • Adverse event data was collected up to 3 months during each patient's participation.	1.9% 2/104 • Number of events 2 • Adverse event data was collected up to 3 months during each patient's participation.
Psychiatric disorders Depression, increased depressive thoughts and feelings	0.00% 0/184 • Adverse event data was collected up to 3 months during each patient's participation.	2.9% 3/104 • Number of events 3 • Adverse event data was collected up to 3 months during each patient's participation.
Renal and urinary disorders Urinary symptoms - frequency	0.54% 1/184 • Number of events 1 • Adverse event data was collected up to 3 months during each patient's participation.	0.96% 1/104 • Number of events 1 • Adverse event data was collected up to 3 months during each patient's participation.
Surgical and medical procedures Cholecystitis	0.54% 1/184 • Number of events 1 • Adverse event data was collected up to 3 months during each patient's participation.	0.00% 0/104 • Adverse event data was collected up to 3 months during each patient's participation.
Psychiatric disorders Poor concentration	0.00% 0/184 • Adverse event data was collected up to 3 months during each patient's participation.	1.9% 2/104 • Number of events 2 • Adverse event data was collected up to 3 months during each patient's participation.
Psychiatric disorders Decreased energy	0.00% 0/184 • Adverse event data was collected up to 3 months during each patient's participation.	1.9% 2/104 • Number of events 2 • Adverse event data was collected up to 3 months during each patient's participation.
Psychiatric disorders Restlessness	0.00% 0/184 • Adverse event data was collected up to 3 months during each patient's participation.	1.9% 2/104 • Number of events 2 • Adverse event data was collected up to 3 months during each patient's participation.
Psychiatric disorders Increased score in suicidal thoughts question	2.2% 4/184 • Number of events 4 • Adverse event data was collected up to 3 months during each patient's participation.	1.9% 2/104 • Number of events 2 • Adverse event data was collected up to 3 months during each patient's participation.
General disorders Fainting during blood draw	1.1% 2/184 • Number of events 2 • Adverse event data was collected up to 3 months during each patient's participation.	0.00% 0/104 • Adverse event data was collected up to 3 months during each patient's participation.
General disorders Dry Mouth	1.1% 2/184 • Number of events 2 • Adverse event data was collected up to 3 months during each patient's participation.	0.96% 1/104 • Number of events 1 • Adverse event data was collected up to 3 months during each patient's participation.
Skin and subcutaneous tissue disorders Edema/bloating after starting meds & increased on full dose	0.54% 1/184 • Number of events 1 • Adverse event data was collected up to 3 months during each patient's participation.	0.00% 0/104 • Adverse event data was collected up to 3 months during each patient's participation.
Psychiatric disorders Altered mental status due to hepatic encephalopathy w/o coma	0.54% 1/184 • Number of events 1 • Adverse event data was collected up to 3 months during each patient's participation.	0.00% 0/104 • Adverse event data was collected up to 3 months during each patient's participation.
Skin and subcutaneous tissue disorders Skin Itchiness	1.6% 3/184 • Number of events 3 • Adverse event data was collected up to 3 months during each patient's participation.	0.00% 0/104 • Adverse event data was collected up to 3 months during each patient's participation.
Nervous system disorders Dizziness	1.1% 2/184 • Number of events 2 • Adverse event data was collected up to 3 months during each patient's participation.	0.96% 1/104 • Number of events 1 • Adverse event data was collected up to 3 months during each patient's participation.
Psychiatric disorders Relapse - alcohol consumption	2.2% 4/184 • Number of events 5 • Adverse event data was collected up to 3 months during each patient's participation.	3.8% 4/104 • Number of events 5 • Adverse event data was collected up to 3 months during each patient's participation.
Nervous system disorders Drowsiness	0.54% 1/184 • Number of events 1 • Adverse event data was collected up to 3 months during each patient's participation.	0.00% 0/104 • Adverse event data was collected up to 3 months during each patient's participation.
Skin and subcutaneous tissue disorders Red Rash	2.2% 4/184 • Number of events 4 • Adverse event data was collected up to 3 months during each patient's participation.	0.00% 0/104 • Adverse event data was collected up to 3 months during each patient's participation.
Skin and subcutaneous tissue disorders Face swelling	0.54% 1/184 • Number of events 1 • Adverse event data was collected up to 3 months during each patient's participation.	0.00% 0/104 • Adverse event data was collected up to 3 months during each patient's participation.
Musculoskeletal and connective tissue disorders Pulled Hamstring	0.54% 1/184 • Number of events 1 • Adverse event data was collected up to 3 months during each patient's participation.	0.96% 1/104 • Number of events 1 • Adverse event data was collected up to 3 months during each patient's participation.
Infections and infestations Piercing infection	0.00% 0/184 • Adverse event data was collected up to 3 months during each patient's participation.	0.96% 1/104 • Number of events 1 • Adverse event data was collected up to 3 months during each patient's participation.
Renal and urinary disorders Constipation	0.54% 1/184 • Number of events 1 • Adverse event data was collected up to 3 months during each patient's participation.	0.00% 0/104 • Adverse event data was collected up to 3 months during each patient's participation.
Product Issues Possible Acamprosate side effects	0.54% 1/184 • Number of events 1 • Adverse event data was collected up to 3 months during each patient's participation.	0.00% 0/104 • Adverse event data was collected up to 3 months during each patient's participation.
General disorders ED visit for tooth pain	0.54% 1/184 • Number of events 1 • Adverse event data was collected up to 3 months during each patient's participation.	0.00% 0/104 • Adverse event data was collected up to 3 months during each patient's participation.
Musculoskeletal and connective tissue disorders Demyelination	0.54% 1/184 • Number of events 1 • Adverse event data was collected up to 3 months during each patient's participation.	0.00% 0/104 • Adverse event data was collected up to 3 months during each patient's participation.
Nervous system disorders Pt found unconscious & unresponsive 40-45 minutes after blood draw	0.00% 0/184 • Adverse event data was collected up to 3 months during each patient's participation.	0.96% 1/104 • Number of events 1 • Adverse event data was collected up to 3 months during each patient's participation.
Psychiatric disorders Distress from symptoms with request that study psychiatrist contact them	1.1% 2/184 • Number of events 2 • Adverse event data was collected up to 3 months during each patient's participation.	0.96% 1/104 • Number of events 1 • Adverse event data was collected up to 3 months during each patient's participation.
Musculoskeletal and connective tissue disorders Shoulder injury/pain	0.54% 1/184 • Number of events 1 • Adverse event data was collected up to 3 months during each patient's participation.	0.96% 1/104 • Number of events 1 • Adverse event data was collected up to 3 months during each patient's participation.
Musculoskeletal and connective tissue disorders Chronic Knee injury (history of)	0.54% 1/184 • Number of events 1 • Adverse event data was collected up to 3 months during each patient's participation.	0.00% 0/104 • Adverse event data was collected up to 3 months during each patient's participation.
Psychiatric disorders Emotional upset	1.1% 2/184 • Number of events 2 • Adverse event data was collected up to 3 months during each patient's participation.	0.00% 0/104 • Adverse event data was collected up to 3 months during each patient's participation.
Infections and infestations COVID 19	0.00% 0/184 • Adverse event data was collected up to 3 months during each patient's participation.	0.96% 1/104 • Number of events 1 • Adverse event data was collected up to 3 months during each patient's participation.
Social circumstances Patient Health Information (PHI) shared with non-study member	0.54% 1/184 • Number of events 1 • Adverse event data was collected up to 3 months during each patient's participation.	0.00% 0/104 • Adverse event data was collected up to 3 months during each patient's participation.
General disorders Mouth injury and spitting blood	0.00% 0/184 • Adverse event data was collected up to 3 months during each patient's participation.	0.96% 1/104 • Number of events 1 • Adverse event data was collected up to 3 months during each patient's participation.
Psychiatric disorders Irritation, feelings of crabbiness	0.00% 0/184 • Adverse event data was collected up to 3 months during each patient's participation.	0.96% 1/104 • Number of events 1 • Adverse event data was collected up to 3 months during each patient's participation.
Respiratory, thoracic and mediastinal disorders COPD exacerbation	0.54% 1/184 • Number of events 1 • Adverse event data was collected up to 3 months during each patient's participation.	0.00% 0/104 • Adverse event data was collected up to 3 months during each patient's participation.
Musculoskeletal and connective tissue disorders Ankle injury	0.54% 1/184 • Number of events 1 • Adverse event data was collected up to 3 months during each patient's participation.	0.00% 0/104 • Adverse event data was collected up to 3 months during each patient's participation.
Skin and subcutaneous tissue disorders Bruise around left eye	0.54% 1/184 • Number of events 1 • Adverse event data was collected up to 3 months during each patient's participation.	0.00% 0/104 • Adverse event data was collected up to 3 months during each patient's participation.
Psychiatric disorders Panic attack with disassociation	0.00% 0/184 • Adverse event data was collected up to 3 months during each patient's participation.	0.96% 1/104 • Number of events 1 • Adverse event data was collected up to 3 months during each patient's participation.