Academic Journal
A Neuroimmune Modulator for Alcohol Use Disorder: A Randomized Clinical Trial.
| Τίτλος: | A Neuroimmune Modulator for Alcohol Use Disorder: A Randomized Clinical Trial. |
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| Συγγραφείς: | Ray LA; Department of Psychology, University of California at Los Angeles.; Department of Psychiatry and Biobehavioral Sciences, University of California at Los Angeles.; Brain Research Institute, University of California at Los Angeles., Meredith LR; Department of Psychology, University of California at Los Angeles., Grodin EN; Department of Psychology, University of California at Los Angeles.; Department of Psychiatry and Biobehavioral Sciences, University of California at Los Angeles.; Brain Research Institute, University of California at Los Angeles., Belnap MA; Department of Psychology, University of California at Los Angeles.; Brain Research Institute, University of California at Los Angeles., Nieto SJ; Department of Psychology, University of California at Los Angeles., Baskerville WA; Department of Psychology, University of California at Los Angeles., Donato S; Department of Psychology, University of California at Los Angeles., Shoptaw SJ; Center for Behavioral and Addiction Medicine, Department of Family Medicine, University of California at Los Angeles., Gillis AJ; Department of Psychiatry and Biobehavioral Sciences, University of California at Los Angeles., Irwin MR; Department of Psychology, University of California at Los Angeles.; Department of Psychiatry and Biobehavioral Sciences, University of California at Los Angeles., Miotto K; Department of Psychiatry and Biobehavioral Sciences, University of California at Los Angeles., Enders CK; Department of Psychology, University of California at Los Angeles. |
| Πηγή: | JAMA network open [JAMA Netw Open] 2025 Apr 01; Vol. 8 (4), pp. e257523. Date of Electronic Publication: 2025 Apr 01. |
| Τύπος έκδοσης: | Journal Article; Randomized Controlled Trial; Clinical Trial, Phase II; Research Support, Non-U.S. Gov't; Research Support, N.I.H., Extramural |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: American Medical Association Country of Publication: United States NLM ID: 101729235 Publication Model: Electronic Cited Medium: Internet ISSN: 2574-3805 (Electronic) Linking ISSN: 25743805 NLM ISO Abbreviation: JAMA Netw Open Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Chicago, IL : American Medical Association, [2018]- |
| Ιατρικοί όροι (MeSH): | Alcoholism*/drug therapy , Alcoholism*/immunology , Pyridines*/therapeutic use , Pyridines*/pharmacology , Phosphodiesterase Inhibitors*/therapeutic use, Humans ; Male ; Female ; Middle Aged ; Adult ; Double-Blind Method ; Treatment Outcome ; Indolizines ; Pyrazoles |
| Περίληψη: | Importance: The neuroimmune system represents a promising target for novel medications for alcohol use disorder (AUD). Ibudilast is a neuroimmune modulator which selectively inhibits phosphodiesterases (PDE) 3, PDE4, PDE10, and PDE11, and macrophage migration inhibitory factor (MIF). Objective: To test the efficacy of ibudilast for AUD compared with placebo. Design, Setting, and Participants: This randomized clinical trial was a double-masked, phase 2 trial conducted at an academic research center between October 2018 and April 2023. Eligible participants were adults seeking treatment for moderate or severe AUD. After completing the 12-week treatment period, participants were followed up for an additional 4 weeks. Interventions: Ibudilast taken twice daily in 50 mg doses for 12 weeks vs placebo. Main Outcomes and Measures: Percentage of heavy drinking days; secondary efficacy outcomes included drinks per day, drinks per drinking day, and percentage of days abstinent. Registered exploratory analyses tested whether the effects of ibudilast of drinking outcomes were moderated by baseline depressive symptomatology. Registered exploratory analyses also tested whether ibudilast reduced inflammation compared with placebo, as indicated by circulating levels of proinflammatory markers over the 12-week trial. Additionally, a post hoc exploratory analysis investigated whether sex moderated the effect of ibudilast on drinking outcomes. Data were analyzed between October 2018 and April 2023. Results: A total of 102 participants were enrolled in the study (mean [SD] age, 44.3 [10.8] years; 61 male [59.8%]; 24 Black [23.5%], 32 Hispanic [31.4%], 52 White [51.0%]). Baseline demographic characteristics and alcohol use patterns did not significantly differ between the 2 medication conditions. There was no significant difference between ibudilast vs placebo on percentage of heavy drinking days (β = 0.06, SE = 0.08 [95% CI, -0.09 to 0.21]; P = .46). There were no significant differences between ibudilast vs placebo on registered secondary outcomes. There were no significant effects of ibudilast compared with placebo on peripheral markers of inflammation. Moderation analyses found that baseline depressive symptomology (time 2 for drinks per drinking day: β = 0.25, SE = 0.11 [95% CI, 0.03 to 0.48]; P = .03) and sex (β = -2.48, SE = 1.07 [95% CI, -4.59 to -0.37]; P = .02) may moderate the effects of ibudilast. Conclusions and Relevance: In this randomized clinical trial of ibudilast for the treatment of AUD, there was no support for the efficacy of ibudilast over placebo; additionally, no effect of ibudilast on markers of peripheral inflammation was observed. As novel treatments for AUD are developed for novel molecular targets, their effects may depend on mechanisms and moderators of efficacy. Trial Registration: ClinicalTrials.gov Identifier: NCT03594435. |
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| Grant Information: | K01 AA029712 United States AA NIAAA NIH HHS; T32 HD091059 United States HD NICHD NIH HHS; R01 AA026190 United States AA NIAAA NIH HHS; F32 AA029288 United States AA NIAAA NIH HHS; K24 AA025704 United States AA NIAAA NIH HHS; F31 AA029295 United States AA NIAAA NIH HHS |
| Molecular Sequence: | ClinicalTrials.gov NCT03594435 |
| Substance Nomenclature: | M0TTH61XC5 (ibudilast) 0 (Pyridines) 0 (Phosphodiesterase Inhibitors) 0 (Indolizines) 0 (Pyrazoles) |
| Entry Date(s): | Date Created: 20250430 Date Completed: 20250430 Latest Revision: 20260416 |
| Update Code: | 20260416 |
| PubMed Central ID: | PMC12044506 |
| DOI: | 10.1001/jamanetworkopen.2025.7523 |
| PMID: | 40305022 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 2574-3805 |
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| DOI: | 10.1001/jamanetworkopen.2025.7523 |