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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.
 
ClinicalTrials.gov Identifier: NCT03248713
Recruitment Status : Terminated (Lack of recruitment)
First Posted : August 14, 2017
Last Update Posted : May 28, 2019
Sponsor:
Information provided by (Responsible Party):
Yale University

Tracking Information
First Submitted Date  ICMJE August 4, 2017
First Posted Date  ICMJE August 14, 2017
Last Update Posted Date May 28, 2019
Actual Study Start Date  ICMJE November 29, 2017
Actual Primary Completion Date May 20, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 11, 2017)
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."
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Glucocorticoid Antagonist Treatment for Tobacco Use Disorder
Official Title  ICMJE Glucocorticoid Antagonist Treatment for Tobacco Use Disorder
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.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Early Phase 1
Study Design  ICMJE 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
Condition  ICMJE Nicotine Dependence
Intervention  ICMJE
  • Drug: Mifepristone
    Mifepristone 600mg 2 tablets will be compared to the placebo
    Other Name: korlym, mifeprex
  • Drug: Placebo
    Placebo sugar 2 tablets will be compared to mifepristone
    Other Name: sugar pill
Study Arms  ICMJE
  • Active Comparator: Mifepristone
    Mifepristone 600 mg/day in 2 tablets
    Intervention: Drug: Placebo
  • Placebo Comparator: Placebo
    matching placebo in 2 tablets
    Intervention: Drug: Mifepristone
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: May 23, 2019)
8
Original Estimated Enrollment  ICMJE
 (submitted: August 11, 2017)
40
Actual Study Completion Date  ICMJE May 20, 2019
Actual Primary Completion Date May 20, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Gender Based Eligibility: Yes
Gender Eligibility Description: Male smokers
Ages  ICMJE 18 Years to 55 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03248713
Other Study ID Numbers  ICMJE MS053
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Yale University
Study Sponsor  ICMJE Yale University
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Mehmet Sofuoglu, M.D.,Ph.D. Yale University
PRS Account Yale University
Verification Date May 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP