Mifepristone for the Prevention of Relapses of Alcohol Drinking

NCT ID: NCT02243709

Last Updated: 2025-01-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 32 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-09-30
• Study Completion Date: 2021-12-21

Brief Summary

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

Conditions

Alcohol Use Disorders (AUD)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: QUADRUPLE

Study Groups

Mifepristone

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

Group Type: ACTIVE_COMPARATOR

Mifepristone 600-mg/day or placebo for a week

Intervention Type: 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

Sugar pill

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

Group Type: PLACEBO_COMPARATOR

Mifepristone 600-mg/day or placebo for a week

Intervention Type: 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

Interventions

Mifepristone 600-mg/day or placebo for a week

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

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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
• History of seizure disorders
• Hypokalemia (low potassium level)<3.5mEq/L
• Participated in any behavioral and/or pharmacological study within minimum the past 30 days
• Neuroendocrine disorders
• Taking corticosteroids
• Bleeding disorders
• Pre-existing QT prolongation on ECG
• History of porphyria (Mifepristone progesterone receptor antagonist is an inducer of CYP-450 and therefore may have the ability to precipitate or exacerbate attacks of acute porphyria)
• Not willing to engage in protected sex (condom). This risk includes both women and men. Mifepristone long half-life (t1/2 = 18 hrs) and its three main metabolites retain considerable affinity toward human progesterone and glucocorticoid receptors, with serum level similar to the parent mifepristone and there are no studies on the presence of mifepristone or metabolites in semen

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Brown University

OTHER

Sponsor Role: lead

Responsible Party

Carolina L Haass-Koffler

Research Fellow

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Carolina L Haass-Koffler, PharmD

Role: PRINCIPAL_INVESTIGATOR

Brown University

Locations

Center for Alcohol and Addiction Studies, Brown University

Providence, Rhode Island, United States

Countries

United States

References

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.

Reference Type: RESULT

PMID: 22048462 (View on PubMed)

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.

Reference Type: RESULT

PMID: 37369125 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 36711869 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

1404001031

Identifier Type: -

Identifier Source: org_study_id