Glucocorticoid Antagonist Treatment for Tobacco Use Disorder

• Status: Terminated
• Trial end date: 2019-05-20
• Target enrollment: 0
• Participant gender: Male

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.

• Phase: Early Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Yale University
• Treatments: Glucocorticoids; Mifepristone

Criteria

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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.