Ibudilast and Withdrawal-Related Dysphoria
| Status: | Recruiting |
|---|---|
| Conditions: | Psychiatric |
| Therapuetic Areas: | Psychiatry / Psychology |
| Healthy: | No |
| Age Range: | 21 - 45 |
| Updated: | 8/31/2018 |
| Start Date: | July 16, 2018 |
| End Date: | June 2020 |
| Contact: | Jessica Jenkins, MS |
| Email: | jenkinsj@ucla.edu |
| Phone: | 310-206-6756 |
Withdrawal-Related Dysphoria as a Moderator of Ibudilast for Alcohol Use Disorder
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.
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.
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.
We found this trial at
1
site
Los Angeles, California 90095
310-825-4321
Principal Investigator: Lara A Ray, PhD
Phone: 310-206-6756
University of California at Los Angeles The University of California, Los Angeles (UCLA) is an...
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