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Glucocorticoid Antagonist Treatment for Tobacco Use Disorder

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT03248713
Recruitment Status : Terminated (Lack of recruitment)
First Posted : August 14, 2017
Last Update Posted : May 28, 2019
Information provided by (Responsible Party):
Yale University

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.

Condition or disease Intervention/treatment Phase
Nicotine Dependence Drug: Mifepristone Drug: Placebo Early Phase 1

Detailed Description:

This will be a double-blind, placebo-controlled study that tests the effects of a 7-day treatment with 600 mg mifepristone, or placebo, on cognitive function, tobacco withdrawal severity and smoking behavior. Once the intake and physical examination is completed and eligibility is determined, subjects will participate in a baseline session to become familiar with the study procedures and to assess baseline measures of withdrawal, smoking urges, pain sensitivity, and cognitive performance. Subjects will be asked to refrain from consuming alcoholic beverages and drugs during their study participation. This will be verified by urine drug screening and breathalyzer before the session and during outpatient visits. If results indicate non-compliance with these study procedures, subjects will be discharged from the study.

Participants will be assessed for compliance with medication treatment, withdrawal severity, recent smoking behavior, and cognitive function during treatment visits on Days 1 and 4. On Day 7, following overnight abstinence from smoking, participants will attend a test session that models relapse to smoking. During this session, subjects will have the option to smoke, or to delay smoking in exchange for monetary compensation (45). To examine if mifepristone's proposed therapeutic effects last beyond the treatment duration (as observed in previous studies), there will be 1-week and 1-month follow-up assessments on smoking behavior, urges to smoke, endocrine biomarkers, and cognitive function.

Participants in each group will complete the laboratory-based, delayed smoking procedure in a designated, negative pressure room in Bldg. 36 of the West Haven VA just after assessing pain sensitivity with the cPT. This sequence allows the cPT to assess pain sensitivity, a potential biomarker of relapse behavior, and to also be used as a mild stressor prior to participation in the smoking relapse model. Participants will be instructed to abstain from smoking after 10 pm the night before Test Sessions. Abstinence will be confirmed the morning of the session by measuring a breath CO level of < 8 ppm.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 8 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description: 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.
Masking: Double (Participant, Investigator)
Masking Description: This is a double blind randomized study
Primary Purpose: Health Services Research
Official Title: Glucocorticoid Antagonist Treatment for Tobacco Use Disorder
Actual Study Start Date : November 29, 2017
Actual Primary Completion Date : May 20, 2019
Actual Study Completion Date : May 20, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Steroids

Arm Intervention/treatment
Active Comparator: Mifepristone
Mifepristone 600 mg/day in 2 tablets
Drug: Placebo
Placebo sugar 2 tablets will be compared to mifepristone
Other Name: sugar pill

Placebo Comparator: Placebo
matching placebo in 2 tablets
Drug: Mifepristone
Mifepristone 600mg 2 tablets will be compared to the placebo
Other Name: korlym, mifeprex

Primary Outcome Measures :
  1. Minnesota Nicotine Withdrawal Symptom Checklist (M-NWSC) [ Time Frame: one week ]
    Smokers will be asked to rate several nicotine withdrawal symptoms on a 100 mm scale, from "not at all" to "extremely."

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   Male
Gender Based Eligibility:   Yes
Gender Eligibility Description:   Male smokers
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03248713

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United States, Connecticut
Veterans Affairs Hospital
West Haven, Connecticut, United States, 06516
Sponsors and Collaborators
Yale University
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Principal Investigator: Mehmet Sofuoglu, M.D.,Ph.D. Yale University
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Responsible Party: Yale University Identifier: NCT03248713    
Other Study ID Numbers: MS053
First Posted: August 14, 2017    Key Record Dates
Last Update Posted: May 28, 2019
Last Verified: May 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Tobacco Use Disorder
Substance-Related Disorders
Chemically-Induced Disorders
Mental Disorders
Abortifacient Agents, Steroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Contraceptives, Oral, Synthetic
Contraceptives, Oral
Contraceptive Agents, Female
Contraceptive Agents
Contraceptives, Postcoital, Synthetic
Contraceptives, Postcoital
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Luteolytic Agents
Menstruation-Inducing Agents