Topiramate Alone and in Combination With the Nicotine Patch for Smoking Cessation: A Pilot Study
Condition: Tobacco Dependence
MeSH terms: Tobacco Use Disorder
Intervention: Placebo (sugar pill); Topiramate; Nicotine patch
Intervention description: patients receive; 25 mg per day for one week, 50 mg per day for one week, 100 mg per day for one week, 200 mg per day for 5 weeks, then one week taper; On the quit date (after 2 weeks of Topiramate medication use), subjects also use 21 mg patch for 7 weeks and on week 8 subjects received 14 mg/day for 3 days then 7 mg for 4 days.
Intervention MeSH terms: Topiramate; Nicotine
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 57.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: nicotine patch; smoking; topiramate

Summary:

      Specific aims:

        1. To obtain pilot data on 4-week continuous quit rates associated with 10 weeks of
           treatment with topiramate or placebo or topiramate plus nicotine patch for smoking
           cessation.

        2. To obtain pilot data on the effects of 10 weeks of topiramate versus placebo versus
           combination of topiramate plus nicotine patch on nicotine withdrawal symptoms, smoking
           satisfaction, and adverse effects during smoking cessation.

        3. To obtain pilot data on weight gain over 10 weeks with topiramate versus placebo versus
           combination of topiramate plus nicotine patch for smoking cessation.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male or female cigarette smoker between the ages of 18 and 65 years inclusive and
             relatively healthy.

          -  Subjects must smoke an average of at least 10 cigarettes per day during the past year
             and during the month prior to the screening visit, with no period of abstinence
             greater than 3 months in the past year.

          -  BMI > 18kg/in2.

          -  Subjects must be free of serious or unstable disease within the past 6 months

          -  Female subjects must be a) postmenopausal for at least two years, or practicing an
             effective method of birth control (e.g., surgically sterile, prescription oral
             contraceptives, contraceptive injections, intrauterine device, spermicide with
             barrier, contraceptive patch, contraceptive ring, male partner sterilization,
             abstinence and agree to continue abstinence or to use an acceptable method of
             contraception, as listed above, should sexual activity commence) before entry and
             throughout the study; have a negative urine pregnancy test at the screening visit. b)
             agree to avoid pregnancy through 30 days after the last dose of study medication, c)
             have a negative urine pregnancy test (β-hCG) at screening or baseline and agree to use
             at least one of the birth control methods as noted in the protocol.

          -  Subjects must be able to be seen as an outpatient, to be assessed in a clinic setting,
             and able and willing to comply with all study visits.

          -  Subjects must be able to provide written consent.

          -  Subjects must be the only member of the household participating in this study.

        Exclusion criteria:

          -  Subjects who are currently suffering from depression or have been diagnosed with
             depression or treated with an antidepressant within the past 12 months.

          -  Subjects who have a past or present history of psychosis, panic disorder, or bipolar
             disorder.

          -  Subjects who have severe chronic obstructive pulmonary disease (COPD).4. Subjects who
             have clinically significant cardiovascular disease in the past 6 months

          -  Subjects who have clinically significant cardiovascular disease in the past 6 months
             which includes: myocardial infarction, coronary artery bypass graft CABG),
             percutaneous transluminal coronary angioplasty (PTCA), severe or unstable angina,
             serious arrhythmia, and clinically significant ECG conduction abnormalities.

          -  Subjects who have uncontrolled hypertension or a systolic blood pressure greater than
             150 mm Hg or a diastolic blood pressure greater than 95 mm Hg at screening or
             baseline.

          -  Subjects who have a history of clinically significant neurological disorders including
             subjects with seizure disorders, cerebrovascular diseases stroke or transient ischemic
             attack) and/or progressive or degenerative neurological disorders (e.g., multiple
             sclerosis) in the past 6 months.

          -  Subjects who have a history of clinically significant endocrine disorders or
             gastrointestinal diseases, including insulin dependent diabetes, uncontrolled
             hyperthyroidism, and active peptic ulcer.

          -  Subjects who have clinically significant hepatic or renal impairment (e.g., an
             estimated creatinine clearance <60 mL/min).

          -  Subjects who have an SGOT (AST) or SGPT (ALT) concentration greater than 1.5 times the
             upper limit of normal.

          -  Subjects who have a history of cancer.

          -  Subjects who are believed to be medically unstable and/or not appropriate for study
             participation in the opinion of the principal investigator.

          -  Subjects who have previously been treated with topiramate for any reason and
             discontinued treatment due to an adverse event or due to a hypersensitivity reaction
             to topiramate.

          -  Subjects with evidence or a history of clinically significant allergic reaction.

          -  Subjects who have an allergy to adhesive tape or a skin disorder that may be
             exacerbated by nicotine patch.

          -  Subjects with a history of drug (except nicotine) or alcohol abuse or dependence
             within the past 12 months.

          -  Subjects with a positive urine drug screen.

          -  Subjects that have been enrolled in a study that included topiramate.

          -  Subjects who have taken or will plan to take another investigational drug within 30
             days or 5 half-lives (whichever is longer) before the Baseline visit or within 30 days
             of study completion.

          -  Subjects who take or plan to take a concomitant medication that is prohibited by this
             protocol.

          -  Subjects who require other medications during the study that might interfere with the
             evaluation of the study drug (for example, nicotine replacement therapy and
             bupropion).

          -  Subjects who used a nicotine replacement product, bupropion, clonidine, or
             nortriptyline within the past 6 months, or participated in a study with an
             experimental drug for smoking cessation within the past one year.

          -  Subjects who intend to use non-cigarette tobacco products (including, for example,
             pipe tobacco, cigars, snuff, chewing tobacco, etc.) or marijuana during study
             participation.

          -  Subjects who intend to donate blood or blood components while receiving study drug or
             within 1 month of the completion of the study treatment.

          -  Subjects who are unable and/or unlikely to comprehend and follow the study protocol,
             which includes a) a subject who, in the investigator's opinion, will be unlikely to
             commit to the duration of the study, b) a subject who, in the investigator's opinion
             should not be enrolled in the study because of the precautions, warnings or
             contraindications outlined in the topiramate package insert.

          -  Subjects who have lactose intolerance.

          -  Subjects with a history of glaucoma.