Dexamethasone to Target Stress and Immune System Mechanisms Underlying Alcohol Craving

Sponsor

Stony Brook University (Other)

Overall Status

Recruiting

CT.gov ID

NCT05305404

Collaborator

(none)

Enrollment

Location

Arms

27.7

Anticipated Duration (Months)

2.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Alcohol Use Disorder	Drug: Dexamethasone Oral Drug: Placebo	Early Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

70 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

This is a two arm assignment where participants are randomized to a single dose dexamethasone (1.5mg) or placeboThis is a two arm assignment where participants are randomized to a single dose dexamethasone (1.5mg) or placebo

Masking:

Double (Participant, Investigator)

Masking Description:

Study is double blind, where participants and investigators are blind to the medication assignment

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Mar 11, 2022

Anticipated Primary Completion Date :

Jun 23, 2024

Anticipated Study Completion Date :

Jun 30, 2024

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Guanfacine single dose of dexamethasone (1.5mg) administered orally	Drug: Dexamethasone Oral 1.5mg oral dexamethasone to be administered once at 11:00PM Other Names: Decadron, Dexamethasone Intensol, Dexasone, Solurex, and Baycadron.
Placebo Comparator: Placebo single dose of placebo administered orally	Drug: Placebo oral placebo to be administered once at 11:00PM

Arm

Intervention/Treatment

Active Comparator: Guanfacine

single dose of dexamethasone (1.5mg) administered orally

Drug: Dexamethasone Oral

1.5mg oral dexamethasone to be administered once at 11:00PM

Other Names:

Decadron, Dexamethasone Intensol, Dexasone, Solurex, and Baycadron.

Placebo Comparator: Placebo

single dose of placebo administered orally

Drug: Placebo

oral placebo to be administered once at 11:00PM

Outcome Measures

Primary Outcome Measures

Alcohol craving as assessed using subjective report following stress exposure [Change from baseline to +5 minutes 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
Alcohol craving as assessed using subjective report following stress exposure [Change from baseline to +15 minutes 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
Alcohol craving as assessed using subjective report following stress exposure [Change from baseline to +30 minutes 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
Alcohol craving as assessed using subjective report following stress exposure [Change from baseline to +5 minutes 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)
Alcohol craving as assessed using subjective report following stress exposure [Change from baseline to +15 minutes 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)
Alcohol craving as assessed using subjective report following stress exposure [Change from baseline to +30 minutes 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)
Hypothalamic-Pituitary-Adrenal (HPA)-axis response to stress exposure as assessed by cortisol [Change from baseline to +5 minutes following stress exposure]
4mls of plasma cortisol will be collected following exposure to stress
HPA axis response to stress exposure as assessed by cortisol [Change from baseline to +15 minutes following stress exposure]
4mls of plasma cortisol will be collected following exposure to stress
HPA axis response to stress exposure as assessed by cortisol [Change from baseline to +30 minutes following stress exposure]
4mls of plasma cortisol will be collected following exposure to stress
HPA axis response to stress exposure as assessed by Adrenocorticotropic Hormone (ACTH) [Change from baseline to +5 minutes following stress exposure]
4mls of plasma ACTH will be collected following exposure to stress
HPA axis response to stress exposure as assessed by ACTH [Change from baseline to +15 minutes following stress exposure]
4mls of plasma ACTH will be collected following exposure to stress
HPA axis response to stress exposure as assessed by ACTH [Change from baseline to +30 minutes following stress exposure]
4mls of plasma ACTH will be collected following exposure to stress
Immune system response to stress exposure as assessed by peripheral cytokines [Change from baseline to +5 minutes following stress exposure]
4mls of plasma Interleukin (IL)-10 will be collected following exposure to stress
Immune system response to stress exposure as assessed by peripheral cytokines [Change from baseline to +15 minutes following stress exposure]
4mls of plasma IL-10 will be collected following exposure to stress
Immune system response to stress exposure as assessed by peripheral cytokines [Change from baseline to +30 minutes following stress exposure]
4mls of plasma IL-10 will be collected following exposure to stress
Immune system response to stress exposure as assessed by peripheral cytokines [Change from baseline to +5 minutes following stress exposure]
4mls of plasma Interleukin 1 receptor antagonist (IL1-ra) will be collected following exposure to stress
Immune system response to stress exposure as assessed by peripheral cytokines [Change from baseline to +15 minutes following stress exposure]
4mls of plasma IL1-ra will be collected following exposure to stress
Immune system response to stress exposure as assessed by peripheral cytokines [Change from baseline to +30 minutes following stress exposure]
4mls of plasma IL1-ra will be collected following exposure to stress
Immune system response to stress exposure as assessed by peripheral cytokines [Change from baseline to +5 minutes following stress exposure]
4mls of plasma IL-6 will be collected following exposure to stress
Immune system response to stress exposure as assessed by peripheral cytokines [Change from baseline to +15 minutes following stress exposure]
4mls of plasma IL-6 will be collected following exposure to stress
Immune system response to stress exposure as assessed by peripheral cytokines [Change from baseline to +30 minutes following stress exposure]
4mls of plasma IL-6 will be collected following exposure to stress
Immune system response to stress exposure as assessed by peripheral cytokines [Change from baseline to +5 minutes following stress exposure]
4mls of plasma Tumor Necrosis Factor alpha (TNFa) will be collected following exposure to stress
Immune system response to stress exposure as assessed by peripheral cytokines [Change from baseline to +15 minutes following stress exposure]
4mls of plasma TNFa will be collected following exposure to stress
Immune system response to stress exposure as assessed by peripheral cytokines [Change from baseline to +30 minutes following stress exposure]
4mls of plasma TNFa will be collected following exposure to stress
Immune system response to stress exposure as assessed by peripheral cytokines [Change from baseline to +5 minutes following stress exposure]
4mls of plasma Tumor Necrosis Factor Receptor 1 (TNFR1) will be collected following exposure to stress
Immune system response to stress exposure as assessed by peripheral cytokines [Change from baseline to +15 minutes following stress exposure]
4mls of plasma TNFR1 will be collected following exposure to stress
Immune system response to stress exposure as assessed by peripheral cytokines [Change from baseline to +30 minutes following stress exposure]
4mls of plasma TNFR1 will be collected following exposure to stress

Secondary Outcome Measures

Anxiety as assessed using subjective report following stress exposure [Change from baseline to +5 minutes 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)
Anxiety as assessed using subjective report following stress exposure [Change from baseline to +15 minutes 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)
Anxiety as assessed using subjective report following stress exposure [Change from baseline to +30 minutes 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)
Negative Mood as assessed using subjective report following stress exposure [Change from baseline to +5 minutes 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
Negative Mood as assessed using subjective report following stress exposure [Change from baseline to +15 minutes 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
Negative Mood as assessed using subjective report following stress exposure [Change from baseline to +30 minutes 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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 55 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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).