Neural Substrates in Nicotine Withdrawal

• Status: Completed
• Trial end date: 2012-10-01
• Target enrollment: 0
• Participant gender: All

Summary

This study will test the hypothesis that a medication called tolcapone (Brand Name: Tasmar) will help reduce cognitive problems that smokers experience when they quit. This study will also determine whether the benefits of this medication differ depending on a smokers' genetic background.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Pennsylvania
• Collaborator: National Institute on Drug Abuse (NIDA)
• Treatments: Nicotine; Tolcapone

Criteria

Inclusion Criteria:

• Smokers who are between 18 and 65 years of age who self-report smoking at least 10 cigarettes (menthol and non-menthol) per day for at least the last 6 months.

• Healthy as determined by the Study Physician, based on a medical evaluation including medical history and physical examination, psychiatric evaluation, and liver function tests (LFTs and GGT enzyme levels).

• Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the combined consent and HIPAA form.

• Women of childbearing potential must consent to use a medically accepted method of birth control while participating in the study (e.g., condoms and spermicide, oral contraceptive, Depo-provera injection, contraceptive patch, tubal ligation) and have 3 months of regular menstrual cycles.

• Capable of providing a Carbon Monoxide (CO) breath test reading greater than 10 parts per million (ppm) at the medical screening visit.

Exclusion Criteria:

Smoking behavior

• Current enrollment or plans to enroll in another research or smoking cessation program in the next 3 months.

• Provide a CO reading less than or equal to 10ppm at the medical screening visit.

• Plans to use nicotine substitutes (gum, patch, lozenge, e-cigarette) while enrolled in the study.

Alcohol/Drug Exclusion:

• History (past 2 years) or current diagnosis of substance abuse and/or currently receiving treatment for substance abuse (alcohol, THC, cocaine, PCP, amphetamines, methamphetamines, MDMA/ecstasy, opiates, methadone, benzodiazepines, tricyclic antidepressants, and barbiturates).

• Current alcohol consumption that exceeds 21 standard drinks/week over the last 6 months.

• Positive urine drug screen (for substances listed previously) at the medical screening visit or either testing day.

• Breath Alcohol Concentration (BrAC) assessment greater than or equal to 0.01 at medical screening visit or either testing day.

Medication Exclusion Criteria:

Current use or recent discontinuation (within last 28 days) of any medication including the following:

• Any form of psychotropic medications including: Antipsychotics; Mood-stabilizers (e.g., lithium, valproic acid, carbamazepine/tegretol); Anti-depressants (tricyclics, SSRI's, MAOI's, non-selective MAOIs, Wellbutrin, St. John's Wort); Anti-anxiety/Anti-panic agents; Anti-obsessive agents; Prescription stimulants (e.g., Provigil, Ritalin); Diet Pills/Anorectics; Systemic Steroids; Daily medication for chronic pain (e.g., opiates) or muscle spasms; Daily use of over the counter stimulants in pill form (e.g., ephedrine)

• Anti-coagulants (e.g., Warfarin)

• Any heart medications (e.g., dobutamine, isoproterenol)

• Daily medication for asthma

• Parkinson's disease medications (e.g., levodopa, methyldopa, apomorphine)

• Sympathomimetic (e.g., albuterol, pseudoephedrine)

• Other smoking cessation medications (Wellbutrin/Zyban, Chantix/varenicline)

Medical Exclusion Criteria:

• Women who are pregnant, planning a pregnancy within the next 3 months, or lactating.

• History or current diagnosis of any Axis 1 disorder as identified by the MINI (Mini International Neuropsychiatric Interview) or self-report. For major depression, only a current diagnosis will be exclusionary.

• History or current diagnosis of Attention-Deficit Hyperactivity Disorder (ADHD).

• Serious or unstable disease (e.g., cancer within the past 6 months [except squamous cell carcinoma], HIV, Parkinson's disease).

• History of epilepsy or a seizure disorder.

• History or current diagnosis (last 6-months) of abnormal rhythms and/or tachycardia (>100 beats/minute); history or current diagnosis of COPD, cardiovascular disease (stroke, angina, coronary heart disease); heart attack in the last 6 months; uncontrolled hypertension (SBP>150 or DBP>90).

• History or current kidney and/or liver failure (including transplant), disease, or impairment (e.g., cirrhosis); history or current diagnosis of hepatitis (excluding hepatitis A); liver function tests more than 20% outside of the normal range; Gamma-glutamyl Transpepsidase (GGT) values greater than 20% outside the normal range.

• Allergy to the study medication, tolcapone (Tasmar).

• History of severe, uncontrolled muscle movements (e.g., uncontrolled jerking, twitching) or a certain severe muscle problem (rhabdomyolysis).

• Low or borderline intellectual functioning - determined by receiving a score of less than 90 on the Shipley Institute of Living Scale (SILS) which correlates with the Wechsler Adult Intelligence Scale-Revised (WAIS-R) Estimated IQ Test (administered at the medical screening visit).

• Experience of dizziness or lightheadedness upon standing on a daily basis.

• Lifetime history of stroke.

fMRI Exclusion Criteria:

• Self-reported history of claustrophobia.

• Left-handedness.

• Color blindness.

• Any impairment preventing subjects from using response pad necessary for cognitive testing.

• Circumstances or conditions that may interfere with magnetic resonance imaging (MRI).

• Having a cochlear implant or wearing bilateral hearing aids.

• Self-reported history of head trauma (including being knocked unconscious for 3 minutes or greater and diagnosis of a concussion) or CNS tumor.

• Self-reported use of pacemakers, certain metallic implants, or presence of metal in the eye as contraindicated for MRI.

• History of gunshot wound.

• Weight greater than 300lbs. at medical screening or either testing day.

• Completion of cognitive testing in study #810493 or #811325 within the last 6 months.

Genetic Profile Exclusion Criteria:

• In order to balance the distribution of males and females, some participants who meet genotype and other eligibility criteria may not be enrolled in the study.

General Exclusion Criteria:

• Any medical condition or concomitant medication that could compromise subject safety or treatment, as determined by the Principal Investigator and/or Study Physician.

• Inability to provide informed consent or complete any of the study tasks as determined by the Principal Investigator and/or Study Physician.