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Ibudilast and Withdrawal-Related Dysphoria

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03489850
Recruitment Status : Recruiting
First Posted : April 6, 2018
Last Update Posted : October 10, 2019
Sponsor:
Information provided by (Responsible Party):
Lara Ray, PhD, University of California, Los Angeles

Brief Summary:

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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Withdrawal-Related Dysphoria as a Moderator of Ibudilast for Alcohol Use Disorder
Actual Study Start Date : July 16, 2018
Estimated Primary Completion Date : June 2020
Estimated Study Completion Date : June 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Alcohol

Arm Intervention/treatment
Active Comparator: Ibudilast
20mg BID Days 1-2 50mg BID Days 3-14
Drug: Ibudilast
Ibudilast (IBUD) is a neuroimmune modulator that inhibits phosphodiesterase-4 and -10 and macrophage migration inhibitory factor.

Placebo Comparator: Placebo
Matched to active
Other: Placebo
Placebo is matched to ibudilast active medication.




Primary Outcome Measures :
  1. 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", "Anxious", "Miserable", and "Sad".



Information from the National Library of Medicine

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Ages Eligible for Study:   21 Years to 45 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age between 21 and 45
  2. Meet DSM-5 criteria for current Moderate-to-Severe AUD
  3. Current Heavy Drinking (> 14 drinks per week for men; > 7 drinks per week for women), as indicated by self-reported drinking for the 30 days prior to screening
  4. Have reliable internet access

Exclusion Criteria:

  1. Currently receiving or seeking treatment for AUD*
  2. Past year DSM-5 diagnosis of any substance use disorder other than alcohol or nicotine
  3. A lifetime diagnosis of schizophrenia, bipolar disorder, or any psychotic disorder
  4. Current use of drugs, other than marijuana, verified by a urine toxicology screen*
  5. Pregnant, nursing, or refusal to use reliable birth control (if female)*
  6. A medical condition that may interfere with safe participation (e.g., unstable cardiac, renal, or liver disease, uncontrolled hypertension, diabetes, or AST, ALT, or GGT ≥ 3 times upper normal limit)
  7. Self-reported recent (i.e. past 30 day) use of medications that are contraindicated with ibudilast*
  8. Non-removable ferromagnetic objects in body
  9. Claustrophobia
  10. Serious head injury or prolonged period of unconsciousness (>30 minutes)

    • Participants who meet these criteria at any point during the course of the study (i.e. after randomization) will be withdrawn from the study for safety purposes.

Information from the National Library of Medicine

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


Contacts
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Contact: Jessica Jenkins, MS 310-206-6756 jenkinsj@ucla.edu
Contact: Erica Grodin, PhD egrodin@psych.ucla.edu

Locations
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United States, California
University of California, Los Angeles Recruiting
Los Angeles, California, United States, 90095
Contact: Jessica Jenkins, MS    310-206-6756    jenkinsj@ucla.edu   
Principal Investigator: Lara A Ray, PhD         
Sponsors and Collaborators
University of California, Los Angeles
Investigators
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Principal Investigator: Lara A Ray, PhD University of California, Los Angeles
  Study Documents (Full-Text)

Documents provided by Lara Ray, PhD, University of California, Los Angeles:
Study Protocol  [PDF] May 10, 2018
Statistical Analysis Plan  [PDF] May 10, 2018

Publications:
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Responsible Party: Lara Ray, PhD, Principal Investigator, University of California, Los Angeles
ClinicalTrials.gov Identifier: NCT03489850    
Other Study ID Numbers: IRB#17-001741
First Posted: April 6, 2018    Key Record Dates
Last Update Posted: October 10, 2019
Last Verified: October 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Ibudilast
Alcoholism
Alcohol Drinking
Drinking Behavior
Alcohol-Related Disorders
Substance-Related Disorders
Chemically-Induced Disorders
Mental Disorders
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Platelet Aggregation Inhibitors
Vasodilator Agents