Treatment for Nicotine Addiction in Women

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.

• Tolcapone (Drug), also known as Tasmar: Tolcapone will be compared to sugar pill
• Sugar Pill (Drug), also known as Placebo: The sugar pill (placebo) will be compared to tolcapone

Primary outcomes

• Withdrawal Symptoms (MNWS Score) [Baseline (ad libitum baseline and pill day 1 (pre-pill)); Abstinent Period (pill days 6, 7, 8)]: 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
• Smoking Urges (BQSU Factor 1) [Baseline (ad libitum baseline and pill day 1 (pre-pill)); Abstinent Period (pill days 6, 7, 8)]: 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.
• Smoking Choice Paradigm: Amount Earned ($) [Pill-Day 8 (end of trial)]: 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).

Sex: Female, ages: 18 Years to 45 Years

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.

Participant flow

Outcome results

• Withdrawal Symptoms (MNWS Score) (Primary), Mean, score on a scale: Tolcapone 13.33 +/- 8.48; Sugar Pill 9.40 +/- 8.12 (p 0.18)
• Smoking Urges (BQSU Factor 1) (Primary), Mean, score on a scale: Tolcapone 19.69 +/- 9.89; Sugar Pill 13.42 +/- 7.44 (p 0.03)
• Smoking Choice Paradigm: Amount Earned ($) (Primary), Mean, Dollars ($): Tolcapone 7.41 +/- 0.26; Sugar Pill 7.06 +/- 0.57 (p 0.037)

Adverse events

Time frame: During the medication phase (8 days) and follow-up (1 week).

Other adverse events by term

6 more terms not shown.

• Study Protocol (PDF, 2019-10-08)
• Statistical Analysis Plan (PDF, 2014-07-07)

• Elise DeVito, Ph.D., Principal investigator, Yale University

NIH grants: R21DA038253