Treatment for Nicotine Addiction in Women

Study Overview
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Brief Summary
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The purpose of this study is to use a medication tolcapone and or placebo to test if the symptoms of nicotine withdrawal lessens , and or changes in smoking urges, and mental reasoning in female smokers over a 72 hour period.

Detailed Description
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The proposed trail will be use a double-blind, placebo-controlled design to conduct the first randomized controlled trial of the COMT inhibitor, tolcapone, in nicotine dependent women. This study will determine if tolcapone is superior to placebo by attenuation the severity of nicotine withdrawal and smoking urges during short-term abstinence. Withdrawal severity will be assessed by a self-report scale and cognitive assessment, including a sustained-attention task. Smoking urges will be assessed by a self-report scale.

Official Title
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COMT Inhibition as a Novel Treatment for Nicotine Addiction in Women

Conditions
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Nicotine Dependence

Intervention / Treatment
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* Drug: Tolcapone
* Drug: Sugar Pill


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must be 18yrs to 45yr old woman, read and write in English. Must smoke at least 5 or more cigarettes a day FTND score at least 4 or higher A CO reading of 10 or higher during screening Must be in good health as verified by medical history, screening exam, screen laboratory tests. Exclusion Criteria: Excluded if using psychotropic medications, have contraindications to tolcapone use (e.g.. liver problems, allergy to tolcapone, history of no traumatic rhabdomyolysis or hyperpyrexia, confusion possibly related to medication), have other substance use disorder, are pregnant or breast feeding, have a current psychotic disorder, bipolar disorder, homicidal or suicidal ideation, have current (past month) substance use disorder, other than nicotine dependence, or are unable to fulfill the scheduled visits and procedures.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Tolcapone<br>100mg tolcapone three times a day for 7 days then 100mg once a day on day 8 | Drug: Sugar Pill<br>* The sugar pill (placebo) will be compared to tolcapone<br>* Other names: Placebo;|
| Placebo Comparator: Sugar Pill<br>Sugar pill | Drug: Tolcapone<br>* Tolcapone will be compared to sugar pill<br>* Other names: Tasmar;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Withdrawal Symptoms (MNWS Score) | The MNWS was the 8 item version, using VAS scales for each item (1-100), and MNWS score calculated as an average of all items (range of possible scores for MWNS at each timepoint was 0-100, with higher MNWS scores at each timepoint indicating more withdrawal symptoms (worse outcome). Timepoints reflect 1.) the baseline (beginning of the trial, not yet receiving any pills, not yet being asked to abstain from smoking; calculated as average of scores from two visits: ad libitum baseline visit and pill day 1 measure which was collected prior to administration of pills) and 2.) the abstinence period (tolcapone or placebo pill days 6-8, during the 60-hr abstinence phase; calculated as average of scores from 3 visits: pill days 6, 7, and 8). Greater increases in scores (increases in withdrawal symptoms) during abstinence period compared to baseline reflects a worse outcome; reduced or stable scores (decreases or a lack of increases in withdrawal symptoms) during the abstinence period compa | Baseline (ad libitum baseline and pill day 1 (pre-pill)); Abstinent Period (pill days 6, 7, 8) | 
| Smoking Urges (BQSU Factor 1) | The Brief Questionnaire on Smoking Urges (BQSU) is a 10 item scale. Factor 1 reflects the urge to smoke for its rewarding properties. Factor 1 is calculated as the sum of five items (items 1, 3, 6, 7, 10), with each item score ranging from 1-7, so Factor 1 scores range from 5-35. Higher scores reflect higher smoking urges and represent a worse outcome. Timepoints reflect 1.) baseline (beginning of trial, not yet receiving pills, not yet abstaining from smoking; calculated as average of scores from ad libitum baseline visit and pill day 1 which was collected prior to administration of pills) and 2.) abstinence period (pill days 6-8, during 60-hr abstinence phase; calculated as average of scores from pill days 6, 7, and 8). Greater increases in scores (increases in smoking urges) during abstinence period compared to baseline reflects a worse outcome; decreases or a lack of increases in smoking urges during the abstinence period compared to baseline reflects a better outcome. | Baseline (ad libitum baseline and pill day 1 (pre-pill)); Abstinent Period (pill days 6, 7, 8) | 
| Smoking Choice Paradigm: Amount Earned ($) | The Smoking Choice Paradigm was done once at the end of the trial (Pill Day 8, at the end of the 60 hr abstinence period). Subjects are given forced choice options between 2 puffs of their own-brand cigarette vs. a token with a monetary value, spaced over a 90 minute period. The maximum amount subjects can earn from this task ranges from $0 to $7.50 (10 forced choice opportunities: smoke 2 puffs vs. earn 75 cent at each choice opportunity). Higher earnings reflect choice of the tokens over smoking, so this reflects a better outcome (i.e., reduced smoking choice). | Pill-Day 8 (end of trial) |