Treatment for Nicotine Addiction in Women
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Tolcapone 100mg tolcapone three times a day for 7 days then 100mg once a day on day 8 |
Drug: Sugar Pill
The sugar pill (placebo) will be compared to tolcapone
Other Names:
|
| Placebo Comparator: Sugar Pill Sugar pill |
Drug: Tolcapone
Tolcapone will be compared to sugar pill
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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).
Eligibility Criteria
Criteria
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Veterans Administration Hospital | West Haven | Connecticut | United States | 06516 |
Sponsors and Collaborators
- Yale University
- US Department of Veterans Affairs
- National Institute on Drug Abuse (NIDA)
Investigators
- Principal Investigator: Elise DeVito, Ph.D., Yale University
Study Documents (Full-Text)
More Information
Publications
None provided.- 1504015628
- 1R21DA038253-01A1
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | 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). |
| Arm/Group Title | Tolcapone | Sugar Pill |
|---|---|---|
| Arm/Group Description | 100mg tolcapone three times a day for 7 days then 100mg once a day on day 8 | Sugar pill (placebo) three times a day for 7 days then once on day 8 |
| Period Title: Overall Study | ||
| STARTED | 19 | 17 |
| Started Pills (Tolcapone or Placebo) | 17 | 15 |
| COMPLETED | 16 | 13 |
| NOT COMPLETED | 3 | 4 |
Baseline Characteristics
| Arm/Group Title | Tolcapone | Sugar Pill | Total |
|---|---|---|---|
| Arm/Group Description | 100mg tolcapone three times a day for 7 days then 100mg once a day on day 8 | Sugar pill (placebo) three times a day for 7 days then once on day 8 | Total of all reporting groups |
| Overall Participants | 19 | 17 | 36 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
32.16
(7.88)
|
33.35
(7.77)
|
32.72
(7.74)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
19
100%
|
17
100%
|
36
100%
|
| Male |
0
0%
|
0
0%
|
0
0%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||
| Hispanic or Latino |
2
10.5%
|
4
23.5%
|
6
16.7%
|
| Not Hispanic or Latino |
17
89.5%
|
13
76.5%
|
30
83.3%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
| Race (NIH/OMB) (Count of Participants) | |||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
| Asian |
0
0%
|
0
0%
|
0
0%
|
| Native Hawaiian or Other Pacific Islander |
1
5.3%
|
0
0%
|
1
2.8%
|
| Black or African American |
14
73.7%
|
7
41.2%
|
21
58.3%
|
| White |
2
10.5%
|
10
58.8%
|
12
33.3%
|
| More than one race |
1
5.3%
|
0
0%
|
1
2.8%
|
| Unknown or Not Reported |
1
5.3%
|
0
0%
|
1
2.8%
|
Outcome Measures
| Title | Withdrawal Symptoms (MNWS Score) |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Study completers (participants who were eligible, randomized to a treatment condition, and completed the study). |
| Arm/Group Title | Tolcapone | Sugar Pill |
|---|---|---|
| Arm/Group Description | 100mg tolcapone three times a day for 7 days then 100mg once a day on day 8 | Sugar pill (placebo) three times a day for 7 days then once on day 8 |
| Measure Participants | 16 | 13 |
| Baseline (no pills, not abstinent) |
13.33
(8.48)
|
9.40
(8.12)
|
| Abstinent Period (on pills, nicotine abstinent)) |
11.95
(11.80)
|
13.29
(13.07)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Tolcapone, Sugar Pill |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.18 |
| Comments | The a priori threshold for statistical significance was p<0.05. | |
| Method | ANOVA | |
| Comments | ||
| Title | Smoking Urges (BQSU Factor 1) |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Study completers (participants who were eligible, randomized to a treatment condition, and completed the study). |
| Arm/Group Title | Tolcapone | Sugar Pill |
|---|---|---|
| Arm/Group Description | 100mg tolcapone three times a day for 7 days then 100mg once a day on day 8 | Sugar pill (placebo) three times a day for 7 days then once on day 8 |
| Measure Participants | 16 | 13 |
| Baseline (no pills, not abstinent) |
19.69
(9.89)
|
13.42
(7.44)
|
| Abstinent Period (on pills, nicotine abstinent)) |
14.50
(10.42)
|
16.04
(9.58)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Tolcapone, Sugar Pill |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.03 |
| Comments | The a priori threshold for statistical significance was p<0.05. | |
| Method | ANOVA | |
| Comments | ||
| Title | Smoking Choice Paradigm: Amount Earned ($) |
|---|---|
| Description | 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 $7.50 (10 forced choice opportunities: smoke 2 puffs vs. earn 75 cent at each choice opportunity). Higher earnings reflect choice of the tokens over smoking, so this reflects a better outcome (i.e., reduced smoking choice). |
| Time Frame | Pill-Day 8 (end of trial) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Study completers (participants who were eligible, randomized to a treatment condition, and completed the study). |
| Arm/Group Title | Tolcapone | Sugar Pill |
|---|---|---|
| Arm/Group Description | 100mg tolcapone three times a day for 7 days then 100mg once a day on day 8 | Sugar pill (placebo) three times a day for 7 days then once on day 8 |
| Measure Participants | 16 | 13 |
| Mean (Standard Deviation) [Dollars ($)] |
7.41
(0.26)
|
7.06
(0.57)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Tolcapone, Sugar Pill |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.037 |
| Comments | The a priori threshold for statistical significance was p<0.05. | |
| Method | ANOVA | |
| Comments | ||
Adverse Events
| Time Frame | During the medication phase (8 days) and follow-up (1 week). | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | Patients 'at risk' for all adverse events are the 'safety population'- which consists of any patient that received study drug post randomization. This would be a total of 32 of 36 patients, 17 in Tolcapone arm and 15 in Sugar Pill arm. | |||
| Arm/Group Title | Tolcapone | Sugar Pill | ||
| Arm/Group Description | 100mg tolcapone three times a day for 7 days then 100mg once a day on day 8 | Sugar pill (placebo) three times a day for 7 days then once on day 8 | ||
All Cause Mortality |
||||
| Tolcapone | Sugar Pill | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/17 (0%) | 0/15 (0%) | ||
Serious Adverse Events |
||||
| Tolcapone | Sugar Pill | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/17 (0%) | 0/15 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Tolcapone | Sugar Pill | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 12/17 (70.6%) | 14/15 (93.3%) | ||
| Cardiac disorders | ||||
| Slow heart rate | 1/17 (5.9%) | 1 | 0/15 (0%) | 0 |
| Irregular or pounding heartbeat | 2/17 (11.8%) | 2 | 1/15 (6.7%) | 1 |
| Chest pain | 1/17 (5.9%) | 1 | 0/15 (0%) | 0 |
| Endocrine disorders | ||||
| Growth of hair in unusual places | 1/17 (5.9%) | 1 | 0/15 (0%) | 0 |
| Eye disorders | ||||
| Teary or dry eyes | 2/17 (11.8%) | 2 | 2/15 (13.3%) | 11 |
| Blurred vision | 1/17 (5.9%) | 1 | 0/15 (0%) | 0 |
| Crossed eyes | 2/17 (11.8%) | 4 | 1/15 (6.7%) | 1 |
| Eye pain | 1/17 (5.9%) | 2 | 0/15 (0%) | 0 |
| Involuntary eye movements | 1/17 (5.9%) | 2 | 0/15 (0%) | 0 |
| Near Sightedness | 2/17 (11.8%) | 3 | 0/15 (0%) | 0 |
| Gastrointestinal disorders | ||||
| Stomach pain | 3/17 (17.6%) | 4 | 1/15 (6.7%) | 1 |
| Upset stomach | 1/17 (5.9%) | 2 | 4/15 (26.7%) | 6 |
| Vomiting | 2/17 (11.8%) | 3 | 1/15 (6.7%) | 1 |
| Loss of appetite | 2/17 (11.8%) | 3 | 2/15 (13.3%) | 3 |
| Constipation | 1/17 (5.9%) | 1 | 1/15 (6.7%) | 1 |
| Diarrhea | 2/17 (11.8%) | 3 | 2/15 (13.3%) | 2 |
| Excessive Hunger | 4/17 (23.5%) | 4 | 3/15 (20%) | 6 |
| Dry Mouth | 3/17 (17.6%) | 4 | 3/15 (20%) | 4 |
| Change in ability to taste food | 2/17 (11.8%) | 4 | 2/15 (13.3%) | 2 |
| Gas | 3/17 (17.6%) | 5 | 3/15 (20%) | 8 |
| Nausea | 3/17 (17.6%) | 4 | 2/15 (13.3%) | 2 |
| General disorders | ||||
| Nosebleed | 1/17 (5.9%) | 1 | 1/15 (6.7%) | 1 |
| Runny nose | 0/17 (0%) | 0 | 4/15 (26.7%) | 5 |
| Sweating | 2/17 (11.8%) | 3 | 1/15 (6.7%) | 1 |
| Tremors or shakiness | 1/17 (5.9%) | 1 | 0/15 (0%) | 0 |
| Tingling in fingers or toes | 3/17 (17.6%) | 6 | 1/15 (6.7%) | 1 |
| Sore Throat | 2/17 (11.8%) | 3 | 3/15 (20%) | 7 |
| Fever | 1/17 (5.9%) | 1 | 2/15 (13.3%) | 3 |
| Chills | 2/17 (11.8%) | 4 | 2/15 (13.3%) | 2 |
| Feeling dizzy or faint or lighheaded | 2/17 (11.8%) | 3 | 3/15 (20%) | 4 |
| Numbness or tingling around mouth | 1/17 (5.9%) | 2 | 0/15 (0%) | 0 |
| Slowed movements | 1/17 (5.9%) | 2 | 0/15 (0%) | 0 |
| Sudden hunger | 3/17 (17.6%) | 4 | 1/15 (6.7%) | 3 |
| Trouble speaking or swallowing | 1/17 (5.9%) | 1 | 0/15 (0%) | 0 |
| Swelling of tongue | 1/17 (5.9%) | 1 | 0/15 (0%) | 0 |
| Trouble with gums | 1/17 (5.9%) | 1 | 1/15 (6.7%) | 1 |
| Extreme thirst | 1/17 (5.9%) | 1 | 2/15 (13.3%) | 2 |
| Metabolism and nutrition disorders | ||||
| Weightloss | 2/17 (11.8%) | 3 | 0/15 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||
| Back muscle or bone pain | 5/17 (29.4%) | 9 | 3/15 (20%) | 7 |
| Weakness | 1/17 (5.9%) | 2 | 0/15 (0%) | 0 |
| Trouble walking | 1/17 (5.9%) | 2 | 1/15 (6.7%) | 1 |
| Psychiatric disorders | ||||
| Nervousness | 0/17 (0%) | 0 | 5/15 (33.3%) | 9 |
| Restlessness | 2/17 (11.8%) | 2 | 7/15 (46.7%) | 12 |
| Difficulty sleeping | 3/17 (17.6%) | 3 | 9/15 (60%) | 12 |
| Feeling drowsy | 5/17 (29.4%) | 6 | 5/15 (33.3%) | 9 |
| Extreme tiredness (fatigue) | 5/17 (29.4%) | 6 | 3/15 (20%) | 4 |
| Anger or irritability | 1/17 (5.9%) | 2 | 5/15 (33.3%) | 10 |
| Depressed mood | 1/17 (5.9%) | 2 | 4/15 (26.7%) | 11 |
| Inability to respond to things around you | 0/17 (0%) | 0 | 1/15 (6.7%) | 1 |
| Headache | 3/17 (17.6%) | 3 | 10/15 (66.7%) | 12 |
| Slowed thinking | 1/17 (5.9%) | 1 | 0/15 (0%) | 0 |
| Difficulty concentrating | 1/17 (5.9%) | 2 | 1/15 (6.7%) | 5 |
| Memory problems | 2/17 (11.8%) | 2 | 1/15 (6.7%) | 5 |
| Seizures | 1/17 (5.9%) | 1 | 0/15 (0%) | 0 |
| Agitation | 1/17 (5.9%) | 1 | 1/15 (6.7%) | 1 |
| Aggressive behavior | 2/17 (11.8%) | 3 | 1/15 (6.7%) | 1 |
| Mood swings | 2/17 (11.8%) | 2 | 4/15 (26.7%) | 4 |
| Renal and urinary disorders | ||||
| Problems with urination | 1/17 (5.9%) | 1 | 0/15 (0%) | 0 |
| Kidney Stones | 1/17 (5.9%) | 1 | 0/15 (0%) | 0 |
| Reproductive system and breast disorders | ||||
| Breast pain (female only) | 1/17 (5.9%) | 1 | 1/15 (6.7%) | 2 |
| Painful menstrual periods (female only) | 2/17 (11.8%) | 3 | 2/15 (13.3%) | 7 |
| Missed menstrual periods (female only) | 2/17 (11.8%) | 3 | 1/15 (6.7%) | 5 |
| Excessive Menstrual Bleeding (female only) | 0/17 (0%) | 0 | 1/15 (6.7%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Shortness of Breath | 1/17 (5.9%) | 1 | 0/15 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||
| Rash or skin problem | 2/17 (11.8%) | 4 | 3/15 (20%) | 11 |
| Dandruff | 1/17 (5.9%) | 1 | 1/15 (6.7%) | 8 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Elise E. DeVito, Ph.D./ Associate Research Scientist |
|---|---|
| Organization | Yale University |
| Phone | 203-737-4882 |
| elise.devito@yale.edu |
- 1504015628
- 1R21DA038253-01A1