Nicotine Dependence
Conditions
Brief summary
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
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.
Interventions
DRUGTolcapone
Tolcapone will be compared to sugar pill
DRUGSugar Pill
The sugar pill (placebo) will be compared to tolcapone
Sponsors
US Department of Veterans Affairs
National Institute on Drug Abuse (NIDA)
Yale University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 45 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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). |
Countries
United States
Participant flow
Pre-assignment details
36 consented to be in the study, completed a baseline session, and were randomized to a study arm. However, 4 subjects never actually began the medication trial (i.e., stopped participating prior to receiving any pills (tolcapone or placebo)). 32 subjects began the pill portion of the trial (i.e., started tolcapone or placebo).
Participants by arm
| Arm | Count |
|---|---|
| Tolcapone 100mg tolcapone three times a day for 7 days then 100mg once a day on day 8 | 19 |
| Sugar Pill Sugar pill (placebo) three times a day for 7 days then once on day 8 | 17 |
| Total | 36 |
Baseline characteristics
| Characteristic | Sugar Pill | Total | Tolcapone |
|---|---|---|---|
| Age, Continuous | 33.35 years STANDARD_DEVIATION 7.77 | 32.72 years STANDARD_DEVIATION 7.74 | 32.16 years STANDARD_DEVIATION 7.88 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 6 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 13 Participants | 30 Participants | 17 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants | 21 Participants | 14 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 10 Participants | 12 Participants | 2 Participants |
| Sex: Female, Male Female | 17 Participants | 36 Participants | 19 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 17 | 0 / 15 |
| other Total, other adverse events | 12 / 17 | 14 / 15 |
| serious Total, serious adverse events | 0 / 17 | 0 / 15 |
Outcome results
Primary
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 $7.50 (10 forced choice opportunities: smoke 2 puffs vs. earn 75 cent at each choice opportunity). Higher earnings reflect choice of the tokens over smoking, so this reflects a better outcome (i.e., reduced smoking choice).
Time frame: Pill-Day 8 (end of trial)
Population: Study completers (participants who were eligible, randomized to a treatment condition, and completed the study).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tolcapone | Smoking Choice Paradigm: Amount Earned ($) | 7.41 Dollars ($) | Standard Deviation 0.26 |
| Sugar Pill | Smoking Choice Paradigm: Amount Earned ($) | 7.06 Dollars ($) | Standard Deviation 0.57 |
p-value: 0.037ANOVA
Primary
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.
Time frame: Baseline (ad libitum baseline and pill day 1 (pre-pill)); Abstinent Period (pill days 6, 7, 8)
Population: Study completers (participants who were eligible, randomized to a treatment condition, and completed the study).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tolcapone | Smoking Urges (BQSU Factor 1) | Baseline (no pills, not abstinent) | 19.69 score on a scale | Standard Deviation 9.89 |
| Tolcapone | Smoking Urges (BQSU Factor 1) | Abstinent Period (on pills, nicotine abstinent)) | 14.50 score on a scale | Standard Deviation 10.42 |
| Sugar Pill | Smoking Urges (BQSU Factor 1) | Baseline (no pills, not abstinent) | 13.42 score on a scale | Standard Deviation 7.44 |
| Sugar Pill | Smoking Urges (BQSU Factor 1) | Abstinent Period (on pills, nicotine abstinent)) | 16.04 score on a scale | Standard Deviation 9.58 |
p-value: 0.03ANOVA
Primary
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
Time frame: Baseline (ad libitum baseline and pill day 1 (pre-pill)); Abstinent Period (pill days 6, 7, 8)
Population: Study completers (participants who were eligible, randomized to a treatment condition, and completed the study).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tolcapone | Withdrawal Symptoms (MNWS Score) | Baseline (no pills, not abstinent) | 13.33 score on a scale | Standard Deviation 8.48 |
| Tolcapone | Withdrawal Symptoms (MNWS Score) | Abstinent Period (on pills, nicotine abstinent)) | 11.95 score on a scale | Standard Deviation 11.8 |
| Sugar Pill | Withdrawal Symptoms (MNWS Score) | Baseline (no pills, not abstinent) | 9.40 score on a scale | Standard Deviation 8.12 |
| Sugar Pill | Withdrawal Symptoms (MNWS Score) | Abstinent Period (on pills, nicotine abstinent)) | 13.29 score on a scale | Standard Deviation 13.07 |
p-value: 0.18ANOVA