Ibudilast and Withdrawal-Related Dysphoria
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|ClinicalTrials.gov Identifier: NCT03489850|
Recruitment Status : Completed
First Posted : April 6, 2018
Results First Posted : October 7, 2021
Last Update Posted : October 7, 2021
Alcohol use disorder (AUD) is a prevalent and disabling psychiatric disorder with few, and only moderately efficacious, treatment options. Consequently, the identification of novel treatment targets and the development of rigorous laboratory paradigms to screen and optimize novel therapeutics represents a research priority. Ibudilast (IBUD) is a neuroimmune modulator that inhibits phosphodiesterase-4 and -10 and macrophage migration inhibitory factor. Recently in an AUD sample, IBUD was shown to decrease reactivity to a psychological stressor. Furthermore, IBUD was effective in blunting alcohol reward among participants with greater depressive symptoms, a hallmark symptom of protracted withdrawal. Recently, preclinical research in opiates has demonstrated that drug withdrawal is necessary for microglia activation and neuroinflammation in reward networks, suggesting that IBUD may be most effective among patients who experience withdrawal-related dysphoria. Therefore, this proposed study aims to examine withdrawal-related dysphoria as a moderator of IBUD efficacy in the natural environment measured using Daily Diary Assessment (DDA) approaches. To accomplish this aim, participants meeting criteria for AUD and balanced on the presence of withdrawal-related dysphoria will be enrolled in a double-blinded IBUD trial including consisting of two weeks randomized to medication and DDA assessment. The proposed research aims are:
Aim 1: Test whether IBUD reduces basal negative affect in abstinence, and blunts alcohol-related negative reinforcement. It is hypothesized that IBUD will reduce basal levels of negative affect during alcohol abstinence, and in so doing will interfere with alcohol-induced blunting of negative affectivity as captured during naturalistic drinking episodes.
Aim 2: Test whether IBUD attenuates neural alcohol cue-reactivity. It is hypothesized that IBUD will reduce BOLD activation to alcohol cues in mesocorticolimbic reward circuitry.
Aim 3: Test whether withdrawal-related dysphoria moderates the effects of IBUD. It is hypothesized that IBUD will alleviate basal negative affect, interfere with alcohol-induced negative reinforcement and attenuate BOLD activation to alcohol cues only among participants who experience dysphoria in withdrawal.
Aim 4: Test whether neural activation to alcohol cues is predictive of drinking outcomes. It is hypothesized that individuals with higher mesocorticolimbic activation to alcohol cues will report more drinking in the week following the neuroimaging session.
|Condition or disease||Intervention/treatment||Phase|
|Alcohol Use Disorder||Drug: Ibudilast Other: Placebo||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||52 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Double (Participant, Investigator)|
|Official Title:||Withdrawal-Related Dysphoria as a Moderator of Ibudilast for Alcohol Use Disorder|
|Actual Study Start Date :||July 16, 2018|
|Actual Primary Completion Date :||March 31, 2020|
|Actual Study Completion Date :||March 31, 2020|
Active Comparator: Ibudilast
20mg BID Days 1-2 50mg BID Days 3-14
Ibudilast (IBUD) is a neuroimmune modulator that inhibits phosphodiesterase-4 and -10 and macrophage migration inhibitory factor.
Placebo Comparator: Placebo
Matched to active
Placebo is matched to ibudilast active medication.
- Negative Affect [ Time Frame: Assessed through daily prompts throughout the 2-week study period. ]Negative affect as measured by self-reported ratings of "Downhearted", "Discouraged", "Uneasy", and "Anxious". Each item was rated on a scale from 0 (not at all) to 4 (extremely). The 4 items were summed for the total negative affect score for each day, ranging from 0 - 16. Higher scores indicate more negative mood.
- Heavy Drinking [ Time Frame: 14 days ]Medication effects on number of heavy drinking days. Heavy drinking is defined by the National Institute on Alcohol Abuse and Alcoholism (NIAAA) as ≥5 drinks/day for men and ≥4 drinks/day for women. Values indicate estimated probability of a heavy drinking day across time for each group.
- Any Drinking [ Time Frame: 14 days ]Medication effects on number of days where any drinking was reported. . Values indicate estimated probability of a drinking day across time for each group.
- Ventral Striatum Activation [ Time Frame: Day 8 ]Medication effect on alcohol cue-induced ventral striatal activation. Participants completed an fMRI alcohol cue-reactivity paradigm where they viewed pictures of alcoholic beverages, non-alcoholic beverages, blurred images, and a plus sign. The mean percent signal change between the ALC and BEV blocks was extracted from an a priori defined region of interest: bilateral ventral striatum (VS), 6 mm-radius sphere centered at ±12 6 9 in MNI space.
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): NCT03489850
|United States, California|
|University of California, Los Angeles|
|Los Angeles, California, United States, 90095|
|Principal Investigator:||Lara A Ray, PhD||University of California, Los Angeles|