Dexamethasone to Target Stress and Immune System Mechanisms Underlying Alcohol Craving

NCT05305404 | Unknown Early Phase 1 DMC FDA Drug

• 1 other identifier: R21AA029735
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

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.

Conditions

Alcohol Use Disorder

Keywords

Stress; Dexamethasone; Immune system; Cortisol

Outcome Measures

Primary Outcomes (27)

• 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 Outcomes (6)

• Anxiety as assessed using subjective report following stress exposure

  Change from baseline to +5 minutes following stress exposure

• Anxiety as assessed using subjective report following stress exposure

  Change from baseline to +15 minutes following stress exposure

• Anxiety as assessed using subjective report following stress exposure

  Change from baseline to +30 minutes following stress exposure

• Negative Mood as assessed using subjective report following stress exposure

  Change from baseline to +5 minutes following stress exposure

• Negative Mood as assessed using subjective report following stress exposure

  Change from baseline to +15 minutes following stress exposure

Study Arms (2)

Guanfacine

ACTIVE COMPARATOR

single dose of dexamethasone (1.5mg) administered orally

Drug: Dexamethasone Oral

Placebo

PLACEBO COMPARATOR

single dose of placebo administered orally

Drug: Placebo

Interventions

Dexamethasone Oral DRUG

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

Also known as: Decadron, Dexamethasone Intensol, Dexasone, Solurex, and Baycadron.

Guanfacine

Placebo DRUG

oral placebo to be administered once at 11:00PM

Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Stony Brook University: lead

Study Sites (1)

The Health Sciences Center

Stony Brook, New York, 11794, United States

RECRUITING

MeSH Terms

Conditions

Alcoholism

Interventions

Dexamethasone; Calcium Dobesilate

Condition Hierarchy (Ancestors)

Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds

Study Officials

• Helen C Fox, PhD

  Stony Brook Renaissance School of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Helen C Fox, PhD

CONTACT

631 638 0057; helen.fox@stonybrookmedicine.edu

Erin C Vacey

CONTACT

631 638 1545; erin.vacey@stonybrookmedicine.edu

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Study is double blind, where participants and investigators are blind to the medication assignment
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

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

Study Record Dates

• First Submitted: March 22, 2022
• First Posted: March 31, 2022
• Study Start: March 11, 2022
• Primary Completion: June 23, 2024
• Study Completion: June 30, 2024
• Last Updated: July 28, 2022

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)