Pilot Study of Tolcapone in Smokers
Condition: Nicotine Dependence
MeSH terms: Tobacco Use Disorder
Intervention: Tolcapone; Placebo
Intervention description: Day 1 100mg three times per day Day 2 - Day 7 200mg three times per day Day 8 200mg twice a day Day 9 200mg once a day Day 10 100mg once a day; Day 1 100mg three times per day Day 2 - Day 7 200mg three times per day Day 8 200mg twice a day Day 9 200mg once a day Day 10 100mg once a day
Intervention MeSH terms: Tolcapone
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Care Provider)
Enrollment: 19.0
Sex: All
Minimum age: 18 Years
Maximum age: 55 Years
Healthy volunteers: No
Keywords: Smoking, Abstinence

Summary:

      The goals of this within-subject pilot study are: (1) assess the feasibility and safety of
      administering the Catechol-O-Methyl-Transferase (COMT) inhibitor, tolcapone, to smokers, and
      (2) explore whether tolcapone may reduce abstinence-induced cognitive and affective symptoms
      that promote relapse. A secondary exploratory goal is to assess whether these effects may be
      more pronounced in smokers who carry a high risk COMT genotype for smoking relapse: COMT
      val/val.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Healthy as determined by a responsible physician, based on a medical evaluation
             including history, physical and psychiatric examination, laboratory tests, liver
             function monitoring.

          2. Smokers who are between 18 and 55 years of age and have an IQ greater than 90.

          3. Capable of giving written informed consent, which includes compliance with the
             requirements and restrictions, listed in the consent form.

          4. Based upon self-report, subjects must smoke >10 cigarettes/day and be interested in
             quitting smoking in the next 6 months (i.e., treatment-seekers).

          5. Women of childbearing potential must consent to using a medically accepted method of
             birth control (e.g., condoms and spermicide, oral contraceptive, Depo-provera
             injection, contraceptive patch, tubal ligation).

        Exclusion Criteria:

        Smoking Behavior

          1. Use of chewing tobacco or snuff

          2. Current enrollment or plans to enroll in another smoking cessation program in the next
             month

          3. Plan to use other nicotine substitutes or smoking cessation treatments in the next
             month

          4. Provide a baseline carbon monoxide (CO) reading < 10ppm

        Alcohol/Drug Exclusion Criteria

          1. History of substance abuse and/or currently receiving treatment for substance abuse
             (e.g., alcohol, opioids, cocaine, marijuana, MDMA/ecstasy, or stimulants)

          2. Current alcohol consumption that exceeds >14 standard drinks/week for men and >7
             standard drinks/week for women over the last 6 months

        Medication Exclusion Criteria

          1. Current use or recent discontinuation (within last 4-weeks) of any medication
             including the following:

               -  Any form of psychotropic medications including:

                    -  antipsychotics,

                    -  atypical antipsychotics,

                    -  mood-stabilizers,

                    -  anti-depressants (tricyclics, SSRI's, MAOI's, nonselective MAOIs,
                       Wellbutrin/Zyban),

                    -  anti-panic agents,

                    -  anti-obsessive agents,

                    -  anti-anxiety agents, and

                    -  stimulants (e.g., Provigil, Ritalin)

                    -  Varenicline

               -  Medication for chronic pain

               -  Anti-coagulants (e.g., Warfarin)

               -  Any heart medications

               -  Daily medication for asthma

               -  Apomorphine, dobutamine, isoproterenol, levodopa, methyldopa, or sympathomimetic
                  (e.g., albuterol, pseudoephedrine)

          2. Current use of any smoking cessation medication.

        Medical Exclusion Criteria

          1. Women who are pregnant, planning a pregnancy, or lactating.

          2. History or current diagnosis of psychosis, major depression or bipolar disorder,
             schizophrenia, or any Axis 1 disorder as identified by the MINI.

          3. Serious or unstable disease within the past 6 months (e.g., cancer [except squamous
             cell carcinoma], heart disease, HIV, liver disease, Parkinson's disease).

          4. History of epilepsy or a seizure disorder.

          5. History or current diagnosis (last 6-months) of abnormal rhythms and/or tachycardia
             (>100 beats/minute); history or current diagnosis of chronic obstructive pulmonary
             disease (COPD), cardiovascular disease (stroke, angina, coronary heart disease), heart
             attack in the last 6 months, uncontrolled hypertension (SBP>150 or DBP>90)

          6. History of Kidney and/or liver failure (including transplant) or problems (e.g.,
             cirrhosis); current liver disease or impairment.

          7. History or current diagnosis of hepatitis.

          8. Liver function tests more than 20% outside of the normal range.

          9. Allergies to the study medication, tolcapone (Tasmar).

         10. History of severe, uncontrolled muscle movements (e.g., uncontrolled jerking,
             twitching) or a certain severe muscle problem (rhabdomyolysis).

         11. Experience of dizziness or lightheadedness upon standing on a regular basis (i.e.,
             daily).

        Genetic Profile

          1. Individuals with the heterozygous genotype (val/met) on the catechol-methyl
             transferase (COMT) gene. (Note: this is a small pilot study comparing effects of
             Tolcapone on cognitive performance between val/val (n=8) individuals.) Future research
             done at our center will plan to include those carrying the val/met genotype.

          2. Individuals with the homozygous genotype, met/met, on the COMT gene. As of December
             2008, the study has accrued 8 met/met participants. To balance the genotype groups,
             the study will recruit an equal number of participants with the val/val genotype on
             the COMT gene and not include any further participants with the homozygous, met/met
             genotype. Future research done at our center will plan to include those carrying the
             met/met genotype.

          3. Non-European ancestry as determined by self report at initial telephone screening; we
             expect there to be ethnic differences in allele frequencies for COMT; therefore, as of
             December 2008, to reduce ethnic admixture that could bias the genetic analysis of this
             small sample, the study will be restricted to individuals of European ancestry. All
             participants of non-European ancestry will be referred to other studies at our center.

        General Exclusion

          1. Any medical condition or concomitant medication that could compromise participant
             safety or treatment, as determined by the Principal Investigator and/or Study
             Physician.

          2. Inability to provide informed consent or complete any of the study tasks as determined
             by the Principal Investigator and/or Study Physician.