Glucocorticoid Antagonist Treatment for Tobacco Use Disorder

NCT03248713 | Terminated Early Phase 1 DMC FDA Drug

• 1 other identifier: MS053
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this protocol is to examine whether mifepristone, a medication with glucocorticoid receptor antagonist activity, may be a potential treatment for Tobacco Use Disorder (TUD). Mifepristone has already shown promise as a potential treatment for PTSD (1) and alcohol use disorder (AUD) (2), but no previous studies have examined the therapeutic potential of mifepristone for TUD. This will be a double-blind, placebo-controlled study on the effects of a 7-day treatment with 600 mg mifepristone, or placebo, on cognitive function, tobacco withdrawal severity, and smoking behavior.

Conditions

Nicotine Dependence

Outcome Measures

Primary Outcomes (1)

• Minnesota Nicotine Withdrawal Symptom Checklist (M-NWSC)

  Smokers will be asked to rate several nicotine withdrawal symptoms on a 100 mm scale, from "not at all" to "extremely."

  one week

Study Arms (2)

Mifepristone

ACTIVE COMPARATOR

Mifepristone 600 mg/day in 2 tablets

Drug: Placebo

Placebo

PLACEBO COMPARATOR

matching placebo in 2 tablets

Drug: Mifepristone

Interventions

Mifepristone DRUG

Mifepristone 600mg 2 tablets will be compared to the placebo

Also known as: korlym, mifeprex

Placebo

Placebo DRUG

Placebo sugar 2 tablets will be compared to mifepristone

Also known as: sugar pill

Mifepristone

Eligibility Criteria

• Age: 18 Years - 55 Years
• Gender Eligibility Details: Male smokers
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Male smokers aged 18 to 55 years;
• History of smoking at least 5 cigarettes daily for the past 12 months;
• In good health as verified by medical history, screening examination, and -screening laboratory tests

You may not qualify if:

• History of mifepristone allergy;
• Requirement of any form of regular psychotropic medication (antidepressants, antipsychotics, or anxiolytics) and recent psychiatric history (in the past 6 months);
• Medical illnesses including diabetes, cardiovascular, renal, endocrine, or hepatic disorders;
• Prolonged QTc interval \>450 msec;
• History of adrenal insufficiency or a morning plasma cortisol level less than 5 mcg/dl at screening;
• Hypokalemia at screening (defined as potassium level \< 3.5 mEq/L);
• Current use of clinically significant CYP 3A4 substrates including, simvastatin, lovastatin, cyclosporine, ergotamines, fentanyl, pimozide, quinidine, sirolimus, tacrolimus, triazolam, midazolam.
• use of rifapentin, phenobarbital, phenytoin, carbamazepine, and St. John's Wort.
• Current use of strong 3A4 inhibitors including ketoconazole, itraconazole, nefazodone, ritonavir, nelfinavir, indinavir, atazanavir, amprenavir, fosamprenivir, boceprevir, clarithromycin, conivaptan, lopinavir, mibefradil, posaconazole, saquinavir, telaprevir, telithromycin, voriconazole.
• Treatment with systemic corticosteroids
• Current use of clinically significant CYP 3A inducers (e.g., rifampin, rifabutin);
• Abuse of alcohol or any other illicit or prescription drugs;
• Inability to tolerate cold exposure due to conditions such as peripheral -vascular disease or Raynaud's phenomenon;
• Inability to fulfill all scheduled visits and examination procedures throughout the study period.

Sponsors & Collaborators

• Yale University: lead

Study Sites (1)

Veterans Affairs Hospital

West Haven, Connecticut, 06516, United States

Location

MeSH Terms

Conditions

Tobacco Use Disorder

Interventions

Mifepristone; Sugars

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

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

Study Officials

• Mehmet Sofuoglu, M.D.,Ph.D.

  Yale University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: This is a double blind randomized study
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The primary analyses will use linear mixed models (LMMs). LMMs can handle continuous and dichotomous outcomes, as well as missing data. Analyses will include baseline (pre-treatment) measures of these variables as covariates and other baseline variables where appropriate.

Study Record Dates

• First Submitted: August 4, 2017
• First Posted: August 14, 2017
• Study Start: November 29, 2017
• Primary Completion: May 20, 2019
• Study Completion: May 20, 2019
• Last Updated: May 28, 2019

Record last verified: 2019-05

Locations

US (1)