Alcohol Use Disorder
Conditions
Keywords
ibudilast, treatment, medication development
Brief summary
This study is a double-blind, placebo-controlled randomized clinical trial of Ibudilast (IBUD) (50mg twice a day) for the treatment of Alcohol Use Disorder (AUD). Eligible participants will undergo a 12-week medication treatment period and 5 in-person visits over 16 weeks.
Detailed description
The study design consists of a 12-week, double-blind, placebo-controlled randomized clinical trial of IBUD (50mg twice a day) for the treatment of AUD. The investigators will randomize 132 treatment-seekers with current AUD over the course of 4 years. Participants will complete telephone screening, followed by in-person eligibility assessment, a physical exam for medical eligibility, randomization to study medication or matched placebo, and in-person follow-up visits at 4, 8, and 12 weeks of treatment. Timeline Followback (TLFB) assessment of drinking outcomes will also occur by telephone on weeks 2, 6, and 10. A final safety check visit will occur on week 16, consisting of repeated clinical labs and electrocardiography (ECG).
Interventions
DRUGIbudilast
targets neurotrophin signaling and neuroimmune function
DRUGPlacebo oral capsule
matched to active drug, ibudilast
Sponsors
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
MediciNova
University of California, Los Angeles
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Intervention model description
Two-Arm, Randomized, Double-Blind, Placebo-Controlled
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Be between the ages of 18 and 65 2. Meet current (i.e., past 12 months) Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) diagnostic criteria for alcohol use disorder moderate or severe 3. Be treatment-seeking for alcohol use disorder (AUD) 4. Report drinking at least 28 drinks per week if male (21 drinks per week if female) in the 28 days prior to consent
Exclusion criteria
1. Have a current (last 12 months) DSM-5 diagnosis of substance use disorder for any psychoactive substances other than alcohol and nicotine 2. Have a lifetime DSM-5 diagnosis of schizophrenia, bipolar disorder, or any psychotic disorder 3. Have a positive urine screen for narcotics, amphetamines, or sedative hypnotics; 4. Have clinically significant alcohol withdrawal symptoms as indicated by a score ≥ 10 on the Clinical Institute Withdrawal Assessment for Alcohol-Revised (CIWA-R) 5. Be pregnant, nursing, or planning to become pregnant while taking part in the study; and must agree to one of the following methods of birth control (if female), unless she or partner are surgically sterile: * Oral contraceptives * Contraceptive sponge * Patch * Double barrier * Intrauterine contraceptive device * Etonogestrel implant * Medroxyprogesterone acetate contraceptive injection * Complete abstinence from sexual intercourse * Hormonal vaginal contraceptive ring 6. Have a medical condition that may interfere with safe study participation (e.g., unstable cardiac, renal, or liver disease, uncontrolled hypertension or diabetes) 7. Have aspartate aminotransferase (AST), alanine transaminase (ALT), or gamma-glutamyl transferase (GGT) ≥ 3 times upper normal limit 8. Have attempted suicide in the past 3 years and/or have had serious suicidal intention or plan in the past year 9. Currently be on prescription medication that contraindicates use of ibudilast (IBUD), including alpha or beta agonists, theophylline, or other sympathomimetic 10. Currently be on any medications for AUD or any psychotropic medications (e.g., psychostimulants and benzodiazepines) with the exception of stable antidepressants (stable dose for ≥4 weeks) 11. Have any other circumstances that, in the opinion of the investigators, compromises participant safety.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Heavy Drinking Days | 12 week-treatment period | Heavy drinking days defined as 5+ drinks for men and 4+ for women. Reported outcome measures are proportions of heavy drinking days. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Drinks Per Day | 12-week treatment period | Secondary alcohol consumption endpoint. Outcome measure reported is the proportion of drinks per day. Drinks per day across the trial. Randomization is the first day of study intervention after study eligibility was determined. |
| Drinks Per Drinking Day | 12-week treatment period | Secondary alcohol consumption endpoint. Drinks per drinking day is defined as how many drinks an individual consumed on a day they reported drinking alcohol. |
| Percent Days Abstinent | 12-week treatment period | Secondary alcohol consumption endpoint. Outcome measure reported is the proportion of percent days abstinent. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited via online and print advertisements, local bus campaigns, and targeted recruitment through a laboratory database of previous study participants who agreed to be contacted for further studies.
Pre-assignment details
A stratified randomization list was developed by a statistician and was based on gender, drinking status (moderate drinking defined as ≥ 14 drinks/week for men and ≥ 7 drinks/week for women versus heavy drinking defined as ≥ 28 drinks/week for men and ≥ 21 drinks/week for women).
Participants by arm
| Arm | Count |
|---|---|
| Ibudilast 10mg delayed-release capsules, target dose 50mg twice daily (5 x 10mg capsules twice daily) for 12 weeks.
ibudilast: targets neurotrophin signaling and neuroimmune function | 53 |
| Placebo Oral Capsule matched to experimental drug
Placebo oral capsule: matched to active drug, ibudilast | 49 |
| Total | 102 |
Baseline characteristics
| Characteristic | Placebo Oral Capsule | Ibudilast | Total |
|---|---|---|---|
| Age, Continuous | 45.92 years STANDARD_DEVIATION 11.49 | 42.74 years STANDARD_DEVIATION 10.01 | 44.26 years STANDARD_DEVIATION 10.81 |
| Alcohol Use Disorders Identification Test | 19.16 units on a scale STANDARD_DEVIATION 6.14 | 21.23 units on a scale STANDARD_DEVIATION 8.24 | 20.24 units on a scale STANDARD_DEVIATION 7.35 |
| Any cigarette use | 17 Participants | 18 Participants | 35 Participants |
| Beck's Anxiety Inventory Total | 6.94 units on a scale STANDARD_DEVIATION 7.08 | 8.53 units on a scale STANDARD_DEVIATION 7.87 | 7.76 units on a scale STANDARD_DEVIATION 7.51 |
| Beck's Depression Inventory-II Total | 10.73 units on a scale STANDARD_DEVIATION 7.13 | 11.98 units on a scale STANDARD_DEVIATION 8.55 | 11.38 units on a scale STANDARD_DEVIATION 7.89 |
| Current Depression | 3 Participants | 4 Participants | 7 Participants |
| Drinks per drinking day | 7.52 drinks per drinking day STANDARD_DEVIATION 3.36 | 7.57 drinks per drinking day STANDARD_DEVIATION 4.3 | 7.54 drinks per drinking day STANDARD_DEVIATION 5.36 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 16 Participants | 16 Participants | 32 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 33 Participants | 37 Participants | 70 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Insomnia Severity Index Total | 7.98 units on a scale STANDARD_DEVIATION 5.23 | 9 units on a scale STANDARD_DEVIATION 6.29 | 8.51 units on a scale STANDARD_DEVIATION 5.8 |
| Mild Cannabis Use Disorder | 6 Participants | 6 Participants | 12 Participants |
| Number of drinking days | 22.71 drinking days STANDARD_DEVIATION 7.41 | 22.42 drinking days STANDARD_DEVIATION 7.46 | 22.56 drinking days STANDARD_DEVIATION 7.4 |
| Penn Alcohol Craving Scale Total | 13.73 units on a scale STANDARD_DEVIATION 6.56 | 13.83 units on a scale STANDARD_DEVIATION 5.85 | 13.78 units on a scale STANDARD_DEVIATION 6.17 |
| Percent heavy drinking days | 65.7 percent heavy drinking days STANDARD_DEVIATION 34.89 | 67.5 percent heavy drinking days STANDARD_DEVIATION 34.55 | 66.6 percent heavy drinking days STANDARD_DEVIATION 34.55 |
| Positive THC screen | 11 Participants | 23 Participants | 34 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 11 Participants | 13 Participants | 24 Participants |
| Race (NIH/OMB) More than one race | 6 Participants | 7 Participants | 13 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 5 Participants | 7 Participants |
| Race (NIH/OMB) White | 27 Participants | 25 Participants | 52 Participants |
| Region of Enrollment United States | 49 participants | 53 participants | 102 participants |
| Relief/Habit Drinking | 25 Participants | 27 Participants | 52 Participants |
| Sex: Female, Male Female | 20 Participants | 21 Participants | 41 Participants |
| Sex: Female, Male Male | 29 Participants | 32 Participants | 61 Participants |
| Smokes cigarettes | 20 Participants | 20 Participants | 40 Participants |
| Structured Clinical Interview Alcohol Use Disorder symptom count | 6.27 units on a scale STANDARD_DEVIATION 1.69 | 7.15 units on a scale STANDARD_DEVIATION 2.05 | 6.73 units on a scale STANDARD_DEVIATION 1.93 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 53 | 0 / 49 |
| other Total, other adverse events | 36 / 53 | 27 / 49 |
| serious Total, serious adverse events | 1 / 53 | 1 / 49 |
Outcome results
Primary
Percent Heavy Drinking Days
Heavy drinking days defined as 5+ drinks for men and 4+ for women. Reported outcome measures are proportions of heavy drinking days.
Time frame: 12 week-treatment period
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ibudilast | Percent Heavy Drinking Days | Week 4 Follow-up | 48.57848 percent of heavy drinking days | Standard Deviation 40.24403 |
| Ibudilast | Percent Heavy Drinking Days | Week 8 Follow-up | 47.88029 percent of heavy drinking days | Standard Deviation 40.4752 |
| Ibudilast | Percent Heavy Drinking Days | Week 2 Follow-up | 53.88376 percent of heavy drinking days | Standard Deviation 38.62032 |
| Ibudilast | Percent Heavy Drinking Days | Week 10 Follow-up | 43.36704 percent of heavy drinking days | Standard Deviation 40.82088 |
| Ibudilast | Percent Heavy Drinking Days | Week 6 Follow-up | 40.13970 percent of heavy drinking days | Standard Deviation 41.51441 |
| Ibudilast | Percent Heavy Drinking Days | Week 12 Follow-up | 34.96705 percent of heavy drinking days | Standard Deviation 38.75223 |
| Ibudilast | Percent Heavy Drinking Days | Randomization | 67.4777 percent of heavy drinking days | Standard Deviation 34.54664 |
| Placebo Oral Capsule | Percent Heavy Drinking Days | Week 12 Follow-up | 35.33841 percent of heavy drinking days | Standard Deviation 40.07343 |
| Placebo Oral Capsule | Percent Heavy Drinking Days | Randomization | 65.65447 percent of heavy drinking days | Standard Deviation 34.89305 |
| Placebo Oral Capsule | Percent Heavy Drinking Days | Week 2 Follow-up | 42.96028 percent of heavy drinking days | Standard Deviation 42.12516 |
| Placebo Oral Capsule | Percent Heavy Drinking Days | Week 4 Follow-up | 43.54836 percent of heavy drinking days | Standard Deviation 42.40074 |
| Placebo Oral Capsule | Percent Heavy Drinking Days | Week 6 Follow-up | 45.83959 percent of heavy drinking days | Standard Deviation 39.41569 |
| Placebo Oral Capsule | Percent Heavy Drinking Days | Week 8 Follow-up | 35.80680 percent of heavy drinking days | Standard Deviation 40.36051 |
| Placebo Oral Capsule | Percent Heavy Drinking Days | Week 10 Follow-up | 37.54797 percent of heavy drinking days | Standard Deviation 40.80282 |
Secondary
Drinks Per Day
Secondary alcohol consumption endpoint. Outcome measure reported is the proportion of drinks per day. Drinks per day across the trial. Randomization is the first day of study intervention after study eligibility was determined.
Time frame: 12-week treatment period
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ibudilast | Drinks Per Day | Week 6 Follow-up | 2.9004471 Drinking per day | Standard Deviation 3.1327782 |
| Ibudilast | Drinks Per Day | Randomization | 5.5569643 Drinking per day | Standard Deviation 3.88254 |
| Ibudilast | Drinks Per Day | Week 8 Follow-up | 2.5295239 Drinking per day | Standard Deviation 2.0967361 |
| Ibudilast | Drinks Per Day | Week 4 Follow-up | 2.9416414 Drinking per day | Standard Deviation 3.0687885 |
| Ibudilast | Drinks Per Day | Week 10 Follow-up | 2.3335342 Drinking per day | Standard Deviation 2.2920357 |
| Ibudilast | Drinks Per Day | Week 12 Follow-up | 2.2639331 Drinking per day | Standard Deviation 2.2143404 |
| Ibudilast | Drinks Per Day | Week 2 Follow-up | 2.9712639 Drinking per day | Standard Deviation 2.6163298 |
| Placebo Oral Capsule | Drinks Per Day | Week 12 Follow-up | 1.9131006 Drinking per day | Standard Deviation 2.087459 |
| Placebo Oral Capsule | Drinks Per Day | Randomization | 5.0916392 Drinking per day | Standard Deviation 3.2844504 |
| Placebo Oral Capsule | Drinks Per Day | Week 2 Follow-up | 2.5307298 Drinking per day | Standard Deviation 2.5759514 |
| Placebo Oral Capsule | Drinks Per Day | Week 4 Follow-up | 2.7376672 Drinking per day | Standard Deviation 2.2163207 |
| Placebo Oral Capsule | Drinks Per Day | Week 6 Follow-up | 2.4886257 Drinking per day | Standard Deviation 1.9787647 |
| Placebo Oral Capsule | Drinks Per Day | Week 8 Follow-up | 1.9764896 Drinking per day | Standard Deviation 2.0375665 |
| Placebo Oral Capsule | Drinks Per Day | Week 10 Follow-up | 1.9942146 Drinking per day | Standard Deviation 1.9999379 |
Secondary
Drinks Per Drinking Day
Secondary alcohol consumption endpoint. Drinks per drinking day is defined as how many drinks an individual consumed on a day they reported drinking alcohol.
Time frame: 12-week treatment period
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ibudilast | Drinks Per Drinking Day | Week 4 Follow-up | 5.1232947 drinks per drinking day | Standard Deviation 3.6194523 |
| Ibudilast | Drinks Per Drinking Day | Week 8 Follow-up | 4.9961214 drinks per drinking day | Standard Deviation 3.4733168 |
| Ibudilast | Drinks Per Drinking Day | Week 2 Follow-up | 6.0380129 drinks per drinking day | Standard Deviation 4.2269696 |
| Ibudilast | Drinks Per Drinking Day | Week 10 Follow-up | 4.6825531 drinks per drinking day | Standard Deviation 4.1278832 |
| Ibudilast | Drinks Per Drinking Day | Week 6 Follow-up | 4.8955457 drinks per drinking day | Standard Deviation 3.9859161 |
| Ibudilast | Drinks Per Drinking Day | Week 12 Follow-up | 4.1250715 drinks per drinking day | Standard Deviation 3.1777328 |
| Ibudilast | Drinks Per Drinking Day | Randomization | 7.5702563 drinks per drinking day | Standard Deviation 4.3026834 |
| Placebo Oral Capsule | Drinks Per Drinking Day | Week 12 Follow-up | 3.4113607 drinks per drinking day | Standard Deviation 2.4958175 |
| Placebo Oral Capsule | Drinks Per Drinking Day | Randomization | 7.5157381 drinks per drinking day | Standard Deviation 6.3591036 |
| Placebo Oral Capsule | Drinks Per Drinking Day | Week 2 Follow-up | 4.6825232 drinks per drinking day | Standard Deviation 3.6986878 |
| Placebo Oral Capsule | Drinks Per Drinking Day | Week 4 Follow-up | 4.8648040 drinks per drinking day | Standard Deviation 4.2417622 |
| Placebo Oral Capsule | Drinks Per Drinking Day | Week 6 Follow-up | 4.4555121 drinks per drinking day | Standard Deviation 3.1474673 |
| Placebo Oral Capsule | Drinks Per Drinking Day | Week 8 Follow-up | 3.4954873 drinks per drinking day | Standard Deviation 2.7084074 |
| Placebo Oral Capsule | Drinks Per Drinking Day | Week 10 Follow-up | 3.3946192 drinks per drinking day | Standard Deviation 2.541404 |
Secondary
Percent Days Abstinent
Secondary alcohol consumption endpoint. Outcome measure reported is the proportion of percent days abstinent.
Time frame: 12-week treatment period
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ibudilast | Percent Days Abstinent | Week 8 Follow-up | 49.85351 percent days abstinent. | Standard Deviation 35.34 |
| Ibudilast | Percent Days Abstinent | Randomization | 25.28269 percent days abstinent. | Standard Deviation 24.8623 |
| Ibudilast | Percent Days Abstinent | Week 2 Follow-up | 52.10013 percent days abstinent. | Standard Deviation 31.53534 |
| Ibudilast | Percent Days Abstinent | Week 4 Follow-up | 53.49783 percent days abstinent. | Standard Deviation 33.79115 |
| Ibudilast | Percent Days Abstinent | Week 6 Follow-up | 50.14506 percent days abstinent. | Standard Deviation 34.61062 |
| Ibudilast | Percent Days Abstinent | Week 10 Follow-up | 56.10048 percent days abstinent. | Standard Deviation 34.49246 |
| Ibudilast | Percent Days Abstinent | Week 12 Follow-up | 54.86251 percent days abstinent. | Standard Deviation 34.42088 |
| Placebo Oral Capsule | Percent Days Abstinent | Week 10 Follow-up | 54.35469 percent days abstinent. | Standard Deviation 37.55533 |
| Placebo Oral Capsule | Percent Days Abstinent | Week 6 Follow-up | 49.30242 percent days abstinent. | Standard Deviation 36.06276 |
| Placebo Oral Capsule | Percent Days Abstinent | Randomization | 24.28538 percent days abstinent. | Standard Deviation 24.7113 |
| Placebo Oral Capsule | Percent Days Abstinent | Week 8 Follow-up | 54.99929 percent days abstinent. | Standard Deviation 38.86134 |
| Placebo Oral Capsule | Percent Days Abstinent | Week 2 Follow-up | 51.24152 percent days abstinent. | Standard Deviation 36.33756 |
| Placebo Oral Capsule | Percent Days Abstinent | Week 12 Follow-up | 55.35643 percent days abstinent. | Standard Deviation 38.60974 |
| Placebo Oral Capsule | Percent Days Abstinent | Week 4 Follow-up | 46.76799 percent days abstinent. | Standard Deviation 35.31845 |