Enhancing Self Regulation Among Smokers
Condition: Smoking Cessation; Smoking, Cigarette; Nicotine Dependence
MeSH terms: Tobacco Use Disorder
Intervention: sirolimus; Placebo
Intervention description: Rapamycin (sirolimus) is administered in three 5mg oral capsules. This administration happens once during the first visit.; Placebo is administered in three 5mg oral capsules. This administration happens once during the first visit.
Intervention MeSH terms: Sirolimus
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 22.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to examine the effects of rapamycin (sirolimus) versus a
      placebo, an inactive substance, on responses to smoking cues in individuals with nicotine
      dependence. Rapamycin (sirolimus) is a FDA-approved antibiotic and immunosuppressive drug
      that is currently used to (a) prevent organ transplant recipients from rejecting their
      transplants (b) treat cardiovascular diseases, and (c) treat some forms of cancer. Rapamycin
      (sirolimus) is not FDA-approved for smoking cessation. The use of rapamycin (sirolimus) in
      this study is investigational, meaning that the study medication is not a proven treatment
      for nicotine dependence, however this study will examine the medication's use as a potential
      future treatment for nicotine dependence.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Participants must smoke 10+ cigarettes/day for three or more years

          -  Have a Fagerström Test for Nicotine Dependence score greater than or equal to 4

          -  Be willing to make a cessation attempt

          -  Willing to comply with reinforced abstinence requirements for the three laboratory
             sessions

          -  Willing to use appropriate birth control methods during study participation including
             oral contraceptives, barrier methods (diaphragm or condoms with spermicide or both),
             surgical sterilization, use of an intra-uterine contraceptive device, or complete
             abstinence from sexual intercourse

          -  Remain abstinent from alcohol and all non-prescription drugs prior to medication
             administration and testing sessions

          -  Live with within a 50 mile radius of our research program and have reliable
             transportation

          -  Consent to fast for a two-hour period prior to medication administration

          -  Consent to random assignment to rapamycin (sirolimus) vs. placebo conditions

        Exclusion Criteria:

          -  Dependence on other substances (may meet criteria for abuse)

          -  Undergoing other smoking cessation treatment (e.g., nicotine replacement, Chantix)

          -  Taking medications that may interact with the study medication or alter responding on
             any study measure

          -  Are pregnant, nursing, or of childbearing potential and not using birth control

          -  Present evidence of or a history of significant endocrine, cardiovascular, pulmonary,
             renal or neurological disease, as these conditions may affect heart rate or skin
             conductance measurement

          -  Have significant liver impairment (as indicated by alanine aminotransferase (ALT)
             and/or aspartate aminotransferase (AST) values that are three times the upper limit of
             normal) as rapamycin (sirolimus) is hepatically metabolized

          -  Have an existing infection or immune system disorder as rapamycin (sirolimus) has
             known immunosuppressive properties

          -  Have a history of or current psychotic disorder, severe major depression as evidenced
             by active and profound psychomotor retardation and/or persistent and intense suicidal
             ideation

          -  Currently taking anti-arrhythmic agents, psychostimulants or any other agents known to
             interfere with heart rate and skin conductance monitoring

          -  Have known or suspected hypersensitivity to macrolide compounds (such as
             rapamycin/sirolimus)

          -  Taking medications that could adversely interact with study medication including but
             not limited to significant inhibitors of CYP2D6 or CYP3A4 (voriconazole, fluconazole,
             itraconazole, erythromycin, clarithromycin, diltiazem, verapamil, etc.) or significant
             inducers of CYP3A4, such as anticonvulsants (carbamazepine, phenobarbital, phenytoin,
             etc.) and antibiotics (rifabutin, rifapentine, etc.)

          -  Have a history of thrombocytopenia, idiopathic thrombocytopenia purpura (ITP), or with
             a current platelet count of less than 100,000 cells per mm3,

          -  Have any unhealed wounds, including but not limited to oral ulcers, foot ulcers, or
             recent surgical or trauma wounds

          -  Have any planned surgeries within the next month, including surgical dental procedures