Nicotine DependenceEarly Phase 1NCT03248713
Glucocorticoid Antagonist Treatment for Tobacco Use Disorder
A Early Phase 1 study testing Mifepristone in people with Nicotine Dependence, run by Yale University at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 55 years, men only
- Conditions the study is for
- Nicotine Dependence
- What is being tested?
- Mifepristone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 8 participants
- Where
- 1 siteUnited States
- Study dates
- 29 Nov 2017to 20 May 2019
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- Men only
- No healthy volunteers
- Adult
Who may be able to join
- 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
Who cannot join
- 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);
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- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Veterans Affairs Hospital
West Haven, Connecticut, 06516
About this study
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.
Read the 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.
- Conditions
- Nicotine Dependence
- Being tested
- Mifepristone, Placebo
- Medical subject headings
- Tobacco Use Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MifepristoneDrug
Also called korlym, mifeprex
Mifepristone 600mg 2 tablets will be compared to the placebo
PlaceboDrug
Also called sugar pill
Placebo sugar 2 tablets will be compared to mifepristone
| Study group | Role | What they receive |
|---|---|---|
| Mifepristone | Active comparator | Mifepristone 600 mg/day in 2 tablets Receives: Drug: Placebo |
| Placebo | Placebo comparator | matching placebo in 2 tablets Receives: Drug: Mifepristone |
What is being measured
The primary outcome is the main question the study is designed to answer.
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."
Measured: one week
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Aug 2017
- Study start29 Nov 2017
- Primary completion20 May 2019
- Study completion20 May 2019
Why it stopped: Lack of recruitment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Nicotine DependenceStudies of the same condition, open and under way.
- More trials run by Yale UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Health services research
- Allocation
- Randomised
- Intervention model
- Crossover
- 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 blind
- Who is masked
- Participant, Investigator
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Mehmet Sofuoglu, M.D.,Ph.D., Principal investigator, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03248713
- Sponsor's protocol ID
- MS053
- Status last verified
- May 2019
- First submitted
- 4 Aug 2017
- Last updated
- 28 May 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 May 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Glucocorticoid Antagonist Treatment for Tobacco Use Disorder
- ClinicalTrials.gov ID
- NCT03248713
- Acronym / sponsor ID
- MS053
- Conditions
- Nicotine Dependence
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Lack of recruitment
- Enrolment
- 8 participants (actual)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Study start
- 29 Nov 2017 (actual)
- Primary completion
- 20 May 2019 (actual)
- Study completion
- 20 May 2019 (actual)
- First posted
- 14 Aug 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Health services research
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- 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.
| Arm | Type | Receives |
|---|---|---|
| Mifepristone | Active comparator | Drug: PlaceboMifepristone 600 mg/day in 2 tablets |
| Placebo | Placebo comparator | Drug: Mifepristonematching placebo in 2 tablets |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (14 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MifepristoneAlso: korlym, mifeprexMifepristone 600mg 2 tablets will be compared to the placebo | Drug | Placebo |
| PlaceboAlso: sugar pillPlacebo sugar 2 tablets will be compared to mifepristone | Drug | Mifepristone |
Primary outcome
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."
Results and safety
The study was stopped early (reason given: Lack of recruitment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 May 2019.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mehmet Sofuoglu, M.D.,Ph.D. principal investigator
Yale University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Mifepristone in people with Nicotine Dependence, run by Yale University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 28 May 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Lack of recruitment). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Minnesota Nicotine Withdrawal Symptom Checklist (M-NWSC) (time frame: one week). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 May 2019.