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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
Sponsor:
Information provided by (Responsible Party):
Lara Ray, PhD, University of California, Los Angeles

Tracking Information
First Submitted Date  ICMJE March 8, 2018
First Posted Date  ICMJE April 6, 2018
Results First Submitted Date  ICMJE April 9, 2021
Results First Posted Date  ICMJE October 7, 2021
Last Update Posted Date October 7, 2021
Actual Study Start Date  ICMJE July 16, 2018
Actual Primary Completion Date March 31, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 4, 2021)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: March 29, 2018)
Negative Affect [ Time Frame: Assessed through random telephone prompts throughout the 2-week study period (approximately every 3 hours) ]
Negative affect as measured by self-reported ratings of "Downhearted", "Discouraged", "Uneasy", "Anxious", "Miserable", and "Sad".
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 28, 2021)
  • 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.
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Ibudilast and Withdrawal-Related Dysphoria
Official Title  ICMJE Withdrawal-Related Dysphoria as a Moderator of Ibudilast for Alcohol Use Disorder
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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Alcohol Use Disorder
Intervention  ICMJE
  • Drug: Ibudilast
    Ibudilast (IBUD) is a neuroimmune modulator that inhibits phosphodiesterase-4 and -10 and macrophage migration inhibitory factor.
  • Other: Placebo
    Placebo is matched to ibudilast active medication.
Study Arms  ICMJE
  • Active Comparator: Ibudilast
    20mg BID Days 1-2 50mg BID Days 3-14
    Intervention: Drug: Ibudilast
  • Placebo Comparator: Placebo
    Matched to active
    Intervention: Other: Placebo
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: November 16, 2020)
52
Original Estimated Enrollment  ICMJE
 (submitted: March 29, 2018)
50
Actual Study Completion Date  ICMJE March 31, 2020
Actual Primary Completion Date March 31, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 21 Years to 45 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03489850
Other Study ID Numbers  ICMJE IRB#17-001741
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party Lara Ray, PhD, University of California, Los Angeles
Original Responsible Party Lara Ray, University of California, Los Angeles, Principal Investigator
Current Study Sponsor  ICMJE University of California, Los Angeles
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Lara A Ray, PhD University of California, Los Angeles
PRS Account University of California, Los Angeles
Verification Date October 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP