Dexamethasone to Target Stress and Immune System Mechanisms Underlying Alcohol Craving

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

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.

Study Overview

• Status: Recruiting
• Conditions: Alcohol Use Disorder
• Intervention / Treatment: Drug: Dexamethasone Oral; Drug: Placebo

• Study Type: Interventional
• Enrollment (Anticipated): 70
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Helen C Fox, PhD; Phone Number: 631 638 0057; Email: helen.fox@stonybrookmedicine.edu
• Study Contact Backup: Name: Erin C Vacey; Phone Number: 631 638 1545; Email: erin.vacey@stonybrookmedicine.edu

Study Locations

• United States
  • New York
    • Stony Brook, New York, United States, 11794
      • Recruiting
      • The Health Sciences Center
      • Contact: Helen Fox, PhD; Phone Number: 631-638-0057; Email: helen.fox@stonybrookmedicine.edu
      • Contact: Erin Vacey; Phone Number: 631 638 1545; Email: erin.vacey@stonybrookmedicine.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Stony Brook University
• Investigators: Principal Investigator: Helen C Fox, PhD, Stony Brook Renaissance School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): March 11, 2022
• Primary Completion (Anticipated): June 23, 2024
• Study Completion (Anticipated): June 30, 2024

Study Registration Dates

• First Submitted: March 22, 2022
• First Submitted That Met QC Criteria: March 22, 2022
• First Posted (Actual): March 31, 2022

Study Record Updates

• Last Update Posted (Actual): July 28, 2022
• Last Update Submitted That Met QC Criteria: July 25, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: Stress; Cortisol; Dexamethasone; Immune system
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Drinking Behavior; Alcohol-Related Disorders; Substance-Related Disorders; Alcohol Drinking; Alcoholism; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Protease Inhibitors; Dexamethasone; Dexamethasone acetate; BB 1101
• Other Study ID Numbers: R21AA029735 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No