Mifepristone for the Prevention of Relapses of Alcohol Drinking

NCT02243709 | Completed Phase 1 Results

• 1 other identifier: 1404001031
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this study is to determine if, under stress, alcohol drinking is reduced using mifepristone

Conditions

Alcohol Use Disorders (AUD)

Keywords

Stress, alcohol craving, alcohol use disorders

Outcome Measures

Primary Outcomes (1)

• Number of Participants Experiencing Adverse Events in the Mifepristone Versus Placebo Group as a Measure of Safety and Tolerability

  Safety and tolerability was assessed by the number of participants who experienced adverse events (AEs) while taking the medication, in the mifepristone group verses the placebo group during Visit 2 through and until Visit 5. AEs were assessed at each visit and special attention was paid to any AEs experienced after administration of the oral administration of mifepristone or placebo- Visit 2 to Visit 3 (7 days total) and Visit 4 through Visit 5 (7 days total), and when it was administered with alcohol during the laboratory paradigms at visits 3 and 4.

  5 weeks (one week of drug administration, 3 weeks of washout, followed by one week of drug administration)

Secondary Outcomes (2)

• Alcohol Craving Score on the Alcohol Craving Questionnaire in the Mifepristone Versus Placebo Group

  1 day

• Drinking Consumption in the Mifepristone Verses Placebo Group

  1 day

Study Arms (2)

Mifepristone

ACTIVE COMPARATOR

mifepristone 600-mg/day for a week, in a stress-induced condition triggered by a single dose of 32.4-mg of yohimbine

Drug: Mifepristone 600-mg/day or placebo for a week

Sugar pill

PLACEBO COMPARATOR

matching placebo/day for a week, in a stress-induced condition triggered by a single dose of 32.4-mg of yohimbine

Drug: Mifepristone 600-mg/day or placebo for a week

Interventions

Mifepristone 600-mg/day or placebo for a week DRUG

600-mg of mifepristone for a week, compared to placebo for a week, in a stress-induced condition triggered by a single dose of 32.4 mg of yohimbine

Mifepristone; Sugar pill

Eligibility Criteria

• Age: 21 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female, 21 to 65 years of age
• Females must be postmenopausal for at least one year or surgically sterile (proven by medical record)
• Meet criteria for Alcohol Use Disorders (AUD) DSM-5 diagnosis
• Meet drinking criteria (≥3 drinks/day for men; ≥2 drinks /day for women)
• Must be in good health as confirmed by medical history, physical examination, ECG, lab tests
• Participants must be willing to take oral medication and adhere to the study procedures
• Breath alcohol (BrAC) = 0.00 at each visit
• Be able to understand informed consent and questionnaire in English at an 8th grade level

You may not qualify if:

• Individuals expressing interest in treatment for alcoholism
• Premenopausal women
• Participants who have significant alcohol withdrawal symptoms, defined as a CIWA-Ar score ≥7
• A repeated positive urine drug screen at baseline for any illegal substance except marijuana.
• Individuals diagnosed with a current "severe" Substance Use Disorder (SUD) diagnosis, other than alcohol or nicotine
• Meet DSM-5 criteria for a diagnosis of schizophrenia, bipolar disorder, or other psychoses
• An active illness within the past six months of the screening visit that meets the DSM-5 criteria for a diagnosis of Major Depressive Disorder (MDD) or Anxiety Disorder, or history of attempted suicide
• Clinically significant medical abnormalities: unstable hypertension, clinically significant abnormal ECG, bilirubin \>150% of the upper normal limit, ALT/AST \>300% the UNL, creatinine clearance ≤60 dl/min
• Current use of psychotropic medications that may have an effect on alcohol consumption
• Current use of any medication involved in the metabolism of alcohol such as aldehyde dehydrogenase (ALDH), alcohol dehydrogenase (ADH) and CYP2E1: Cefamandole, Cefotetan, Sulfamethoxazole, Nitroglycerin, Chlorpropamide, Glyburide.
• Current use of any medication (CYP3A4 inhibitor and substrate) that may interact with mifepristone: cyclosporine, fentanyl, heparin, escitalopram, lovastatin, simvastatin, warfarin
• Current use of any medication (CYP2D6 inhibitor and substrate) that may interact with yohimbine: amitriptyline, doxepin, nortriptyline, venlafaxine
• Medical contraindications for use of mifepristone or yohimbine
• A history of adverse reaction or hypersensitivity to mifepristone or yohimbine
• History of suicide

Sponsors & Collaborators

• Brown University: lead

Study Sites (1)

Center for Alcohol and Addiction Studies, Brown University

Providence, Rhode Island, 02912, United States

Location

Related Publications (3)

• Simms JA, Haass-Koffler CL, Bito-Onon J, Li R, Bartlett SE. Mifepristone in the central nucleus of the amygdala reduces yohimbine stress-induced reinstatement of ethanol-seeking. Neuropsychopharmacology. 2012 Mar;37(4):906-18. doi: 10.1038/npp.2011.268. Epub 2011 Nov 2.

  PMID: 22048462 RESULT

• Haass-Koffler CL, Magill M, Cannella N, Brown JC, Aoun EG, Cioe PA, Sinha R, Swift RM, Ciccocioppo R, Leggio L. Mifepristone as a pharmacological intervention for stress-induced alcohol craving: A human laboratory study. Addict Biol. 2023 Jul;28(7):e13288. doi: 10.1111/adb.13288.

  PMID: 37369125 RESULT

• Haass-Koffler CL, Magill M, Cannella N, Brown JC, Aoun EG, Cioe PA, Sinha R, Swift RM, Ciccocioppo R, Leggio L. Mifepristone as a pharmacological intervention for stress-Induced alcohol craving: a translational crossover randomized trial. medRxiv [Preprint]. 2023 Jan 4:2023.01.02.23284122. doi: 10.1101/2023.01.02.23284122.

  PMID: 36711869 DERIVED

MeSH Terms

Conditions

Alcoholism

Interventions

Mifepristone

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Prof. Carolina Haass-Koffler
• Organization: Brown University

carolina_haass-koffler@brown.edu

4155191385

Study Officials

• Carolina L Haass-Koffler, PharmD

  Brown University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Research Fellow

Study Record Dates

• First Submitted: September 12, 2014
• First Posted: September 18, 2014
• Study Start: September 1, 2014
• Primary Completion: December 21, 2021
• Study Completion: December 21, 2021
• Last Updated: January 10, 2025
• Results First Posted: June 1, 2023

Record last verified: 2024-12

Locations

US (1)