Dexamethasone to Target Stress and Immune System Mechanisms Underlying Alcohol Craving

Study Overview
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Brief Summary
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This is a double-blind, placebo-controlled, proof of concept laboratory study to recruit N=70 (35 Males / 35 Females) non-treatment seeking, heavy drinkers with alcohol use disorder (AUD). It is hypothesized that randomization to 1.5mgs dexamethasone versus placebo will decrease alcohol craving during stress by decreasing basal cortisol, increasing anti-inflammatory cytokine levels and potentially normalizing the immune response to stress.

Official Title
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Dexamethasone to Target Stress and Immune System Changes During Early Abstinence in Individuals With Alcohol Use Disorder (AUD)

Conditions
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Alcohol Use Disorder

Intervention / Treatment
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* Drug: Dexamethasone Oral
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Non-treatment seeking heavy drinking men and women with AUD Age range 18-55, Body Mass Index (BMI) of 18-35 Positive ethylglucuronide (EtG) urine toxicology screen for alcohol Able to provide informed written and verbal consent Able to read English and complete study evaluations Good health as verified by screening examination. Exclusion Criteria: Meet criteria for Substance Use Disorder (SUD) or other psychoactive substances, excluding nicotine Unable to remain abstinent for five days Need for a medically assisted detoxification Regular use of steroids, anticonvulsants, sedatives/hypnotics, prescription analgesics, other anti-hypertensives, anti-arrythmics, antiretroviral medications, tricyclic antidepressants, naltrexone, disulfiram, and any other psychoactive medications with the exception of stabilization on Selective Serotonin Re-uptake Inhibitors (SSRIs) Psychotic or severely psychiatrically disabled Significant underlying medical conditions which would be of potential harm Pregnancy or breast feeding women; Women using monophasic contraceptives Electrocardiogram (EKG) evidence of clinically significant conduction abnormalities, (Bazlett's corrected QT (QTc) interval of >450 msec for men and QTc>470 msec for women).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is a two arm assignment where participants are randomized to a single dose dexamethasone (1.5mg) or placebo
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Guanfacine<br>single dose of dexamethasone (1.5mg) administered orally | Drug: Dexamethasone Oral<br>* 1.5mg oral dexamethasone to be administered once at 11:00PM<br>* Other names: Decadron, Dexamethasone Intensol, Dexasone, Solurex, and Baycadron.;|
| Placebo Comparator: Placebo<br>single dose of placebo administered orally | Drug: Placebo<br>* oral placebo to be administered once at 11:00PM<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Alcohol craving as assessed using subjective report following stress exposure | The 8-item Alcohol Urges Questionnaire (AUQ) will be used to measure alcohol craving. There are 8 items, each with a Likert scale response from 1 to 7 (1: Strongly Disagree, 7: Strongly Agree). Total possible score of 56. The higher the score the higher the alcohol craving | Change from baseline to +5 minutes following stress exposure | 
| Alcohol craving as assessed using subjective report following stress exposure | The 8-item Alcohol Urges Questionnaire (AUQ) will be used to measure alcohol craving. There are 8 items, each with a Likert scale response from 1 to 7 (1: Strongly Disagree, 7: Strongly Agree). Total possible score of 56. The higher the score the higher the alcohol craving | Change from baseline to +15 minutes following stress exposure | 
| Alcohol craving as assessed using subjective report following stress exposure | The 8-item Alcohol Urges Questionnaire (AUQ) will be used to measure alcohol craving. There are 8 items, each with a Likert scale response from 1 to 7 (1: Strongly Disagree, 7: Strongly Agree). Total possible score of 56. The higher the score the higher the alcohol craving | Change from baseline to +30 minutes following stress exposure | 
| Alcohol craving as assessed using subjective report following stress exposure | A visual analog scale will be used to measure alcohol craving. Participants will be required to rate how much they are craving alcohol right at this moment. The scale will be anchored from 1 to 10 (1: Not at all, 10: Extremely) | Change from baseline to +5 minutes following stress exposure | 
| Alcohol craving as assessed using subjective report following stress exposure | A visual analog scale will be used to measure alcohol craving. Participants will be required to rate how much they are craving alcohol right at this moment. The scale will be anchored from 1 to 10 (1: Not at all, 10: Extremely) | Change from baseline to +15 minutes following stress exposure | 
| Alcohol craving as assessed using subjective report following stress exposure | A visual analog scale will be used to measure alcohol craving. Participants will be required to rate how much they are craving alcohol right at this moment. The scale will be anchored from 1 to 10 (1: Not at all, 10: Extremely) | Change from baseline to +30 minutes following stress exposure | 
| Hypothalamic-Pituitary-Adrenal (HPA)-axis response to stress exposure as assessed by cortisol | 4mls of plasma cortisol will be collected following exposure to stress | Change from baseline to +5 minutes following stress exposure | 
| HPA axis response to stress exposure as assessed by cortisol | 4mls of plasma cortisol will be collected following exposure to stress | Change from baseline to +15 minutes following stress exposure | 
| HPA axis response to stress exposure as assessed by cortisol | 4mls of plasma cortisol will be collected following exposure to stress | Change from baseline to +30 minutes following stress exposure | 
| HPA axis response to stress exposure as assessed by Adrenocorticotropic Hormone (ACTH) | 4mls of plasma ACTH will be collected following exposure to stress | Change from baseline to +5 minutes following stress exposure | 
| HPA axis response to stress exposure as assessed by ACTH | 4mls of plasma ACTH will be collected following exposure to stress | Change from baseline to +15 minutes following stress exposure | 
| HPA axis response to stress exposure as assessed by ACTH | 4mls of plasma ACTH will be collected following exposure to stress | Change from baseline to +30 minutes following stress exposure | 
| Immune system response to stress exposure as assessed by peripheral cytokines | 4mls of plasma Interleukin (IL)-10 will be collected following exposure to stress | Change from baseline to +5 minutes following stress exposure | 
| Immune system response to stress exposure as assessed by peripheral cytokines | 4mls of plasma IL-10 will be collected following exposure to stress | Change from baseline to +15 minutes following stress exposure | 
| Immune system response to stress exposure as assessed by peripheral cytokines | 4mls of plasma IL-10 will be collected following exposure to stress | Change from baseline to +30 minutes following stress exposure | 
| Immune system response to stress exposure as assessed by peripheral cytokines | 4mls of plasma Interleukin 1 receptor antagonist (IL1-ra) will be collected following exposure to stress | Change from baseline to +5 minutes following stress exposure | 
| Immune system response to stress exposure as assessed by peripheral cytokines | 4mls of plasma IL1-ra will be collected following exposure to stress | Change from baseline to +15 minutes following stress exposure | 
| Immune system response to stress exposure as assessed by peripheral cytokines | 4mls of plasma IL1-ra will be collected following exposure to stress | Change from baseline to +30 minutes following stress exposure | 
| Immune system response to stress exposure as assessed by peripheral cytokines | 4mls of plasma IL-6 will be collected following exposure to stress | Change from baseline to +5 minutes following stress exposure | 
| Immune system response to stress exposure as assessed by peripheral cytokines | 4mls of plasma IL-6 will be collected following exposure to stress | Change from baseline to +15 minutes following stress exposure | 
| Immune system response to stress exposure as assessed by peripheral cytokines | 4mls of plasma IL-6 will be collected following exposure to stress | Change from baseline to +30 minutes following stress exposure | 
| Immune system response to stress exposure as assessed by peripheral cytokines | 4mls of plasma Tumor Necrosis Factor alpha (TNFa) will be collected following exposure to stress | Change from baseline to +5 minutes following stress exposure | 
| Immune system response to stress exposure as assessed by peripheral cytokines | 4mls of plasma TNFa will be collected following exposure to stress | Change from baseline to +15 minutes following stress exposure | 
| Immune system response to stress exposure as assessed by peripheral cytokines | 4mls of plasma TNFa will be collected following exposure to stress | Change from baseline to +30 minutes following stress exposure | 
| Immune system response to stress exposure as assessed by peripheral cytokines | 4mls of plasma Tumor Necrosis Factor Receptor 1 (TNFR1) will be collected following exposure to stress | Change from baseline to +5 minutes following stress exposure | 
| Immune system response to stress exposure as assessed by peripheral cytokines | 4mls of plasma TNFR1 will be collected following exposure to stress | Change from baseline to +15 minutes following stress exposure | 
| Immune system response to stress exposure as assessed by peripheral cytokines | 4mls of plasma TNFR1 will be collected following exposure to stress | Change from baseline to +30 minutes following stress exposure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Anxiety as assessed using subjective report following stress exposure | A visual analog scale will be used to measure anxiety. Participants will be required to rate how nervous, anxious or jittery they are feeling at this moment. The scale will be anchored from 1 to 10 (1: Not at all, 10: Extremely) | Change from baseline to +5 minutes following stress exposure | 
| Anxiety as assessed using subjective report following stress exposure | A visual analog scale will be used to measure anxiety. Participants will be required to rate how nervous, anxious or jittery they are feeling at this moment. The scale will be anchored from 1 to 10 (1: Not at all, 10: Extremely) | Change from baseline to +15 minutes following stress exposure | 
| Anxiety as assessed using subjective report following stress exposure | A visual analog scale will be used to measure anxiety. Participants will be required to rate how nervous, anxious or jittery they are feeling at this moment. The scale will be anchored from 1 to 10 (1: Not at all, 10: Extremely) | Change from baseline to +30 minutes following stress exposure | 
| Negative Mood as assessed using subjective report following stress exposure | The Differential Emotion Scale will be used to measure negative mood. Participants will be required to rate on a 5-point scale the extent to which an emotional word describes the way they feel at the current time. 1: not at all, 5: Extremely | Change from baseline to +5 minutes following stress exposure | 
| Negative Mood as assessed using subjective report following stress exposure | The Differential Emotion Scale will be used to measure negative mood. Participants will be required to rate on a 5-point scale the extent to which an emotional word describes the way they feel at the current time. 1: not at all, 5: Extremely | Change from baseline to +15 minutes following stress exposure | 
| Negative Mood as assessed using subjective report following stress exposure | The Differential Emotion Scale will be used to measure negative mood. Participants will be required to rate on a 5-point scale the extent to which an emotional word describes the way they feel at the current time. 1: not at all, 5: Extremely | Change from baseline to +30 minutes following stress exposure | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Stress, Dexamethasone, Immune system, Cortisol