Nicotine Dependence, Smoking
Conditions
Keywords
nicotine, tobacco, smoking, cessation, N-acetylcysteine, NAC, pharmacotherapy, relapse, tobacco use disorder
Brief summary
The purpose of this study is to assess the effects of administering N-Acetylcysteine (NAC) to assist in initial cessation and/or relapse prevention in adult cigarette smokers.
Detailed description
The aim of this study is to assess the effects of N-acetylcysteine (NAC) on initial cessation and relapse prevention in adult cigarette smokers. Specifically, this study has the following aims: Aim 1) Examine the efficacy of NAC, compared to placebo, in helping smokers achieve three days of continuous abstinence; Aim 2) Among those who maintain initial 3-day abstinence, examine the time to relapse over the 8-week intervention between NAC and placebo groups; Aim 3) Assess 7-day point prevalence abstinence at the 8-week end-of-treatment study visit in order to obtain effect sizes and estimates of variability to power a randomized clinical trial.
Interventions
DRUGN-acetylcysteine (NAC)
NAC or matched placebo will be given to study participants for 8 weeks.
OTHERPlacebo
Matched placebo (2 capsules taken in the morning and evening) will be taken by study participants for eight weeks. All participants will receive brief smoking cessation counseling and support.
Sponsors
National Institute on Drug Abuse (NIDA)
Medical University of South Carolina
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
1. Age 18-65 2. Daily smoker for ≥6 months, smoking approximately ≥5 cigarettes per day on average in the past month or must meet the criteria for nicotine dependence 3. Be interested in quitting smoking (defined as a 2 or above on a 10-point Likert scale assessing readiness and interest in quitting (1=not at all ready/interested, 10=extremely ready/interested) 4. Willing to engage in a 3-day quit attempt as part of study procedures 5. Willing to abstain from cannabis use during study procedures (since inhaled cannabis will affect breath carbon monoxide readings). 6. If female, agreement to use birth control (any form) to avoid pregnancy during study procedures
Exclusion criteria
1. Any serious or unstable medical/psychiatric disorder (including severe substance use disorders, other than tobacco use disorder) in the past month that may interfere with study performance based on PI judgment 2. Current pregnancy or breastfeeding 3. Current use of medications with smoking cessation efficacy 4. Known hypersensitivity to NAC 5. Use of carbamazepine or nitroglycerin (or any other medication deemed to be hazardous if taken with NAC) within 14 days of study participation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Biochemically-verified Abstinence From Smoking on Days 1-3 of the Protocol. | Days 1-3 of the study protocol | Abstinence will be measured through biochemical verification via breath carbon monoxide. Abstinence is defined as a 75% reduction in carbon monoxide values (parts per million) from smoking baseline levels. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Days to Relapse to Smoking Among Abstinent Participants | Days 4-56 of the study protocol | Relapse to smoking will be measured through carbon monoxide-verified relapse at weekly study visits among those who abstained during the 3-day quit attempt. Relapse (return to smoking) will be defined as carbon monoxide values (in parts per million) that do not meet abstinence criteria (i.e., 75% reduction from baseline smoking levels). |
| Number of Participants With 7-day Point Prevalence Abstinence at the 8-week End-of-treatment Visit | Days 49-56 | Seven day point prevalence abstinence will be measured through biochemical verification via breath carbon monoxide and urinary cotinine analysis. Abstinence is defined as a 75% reduction in carbon monoxide values (parts per million) from smoking baseline levels and a negative urine cotinine measure (\<80 ng/mL). |
Countries
United States
Participant flow
Recruitment details
Adult daily cigarette smokers were recruited from the community in Charleston, South Carolina (US).
Pre-assignment details
Following screening, participants completed mobile daily diaries leading up to a Training visit. During this visit, participants were instructed on how to leave a carbon monoxide samples, upload videos, and loaned equipment to complete remote samples. Prior to randomization, 22 participants withdrew, were lost to follow-up or were discontinued.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Matched placebo will be given to half of the study participants.
Placebo: Matched placebo (2 capsules taken in the morning and evening) will be taken by study participants for eight weeks. All participants will receive brief smoking cessation counseling and support. | 55 |
| N-Acetylcysteine (NAC) NAC will be given to half of the study participants. The dose of NAC will be 2400 mg per day (1200 mg taken twice per day as two 600 mg capsules)
N-acetylcysteine (NAC): NAC or matched placebo will be given to study participants for 8 weeks. | 59 |
| Total | 114 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 2 | 3 |
| Overall Study | Withdrawal by Subject | 7 | 12 |
Baseline characteristics
| Characteristic | Placebo | N-Acetylcysteine (NAC) | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 55 Participants | 59 Participants | 114 Participants |
| Age, Continuous | 43.9 Years STANDARD_DEVIATION 11.4 | 40.2 Years STANDARD_DEVIATION 12.2 | 42.0 Years STANDARD_DEVIATION 11.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants | 2 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 49 Participants | 57 Participants | 106 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 12 Participants | 21 Participants | 33 Participants |
| Race (NIH/OMB) More than one race | 3 Participants | 1 Participants | 4 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) White | 38 Participants | 36 Participants | 74 Participants |
| Sex: Female, Male Female | 28 Participants | 30 Participants | 58 Participants |
| Sex: Female, Male Male | 27 Participants | 29 Participants | 56 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 55 | 0 / 59 |
| other Total, other adverse events | 32 / 55 | 33 / 59 |
| serious Total, serious adverse events | 0 / 55 | 0 / 59 |
Outcome results
Primary
Number of Participants With Biochemically-verified Abstinence From Smoking on Days 1-3 of the Protocol.
Abstinence will be measured through biochemical verification via breath carbon monoxide. Abstinence is defined as a 75% reduction in carbon monoxide values (parts per million) from smoking baseline levels.
Time frame: Days 1-3 of the study protocol
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Biochemically-verified Abstinence From Smoking on Days 1-3 of the Protocol. | 8 Participants |
| N-Acetylcysteine (NAC) | Number of Participants With Biochemically-verified Abstinence From Smoking on Days 1-3 of the Protocol. | 6 Participants |
Secondary
Days to Relapse to Smoking Among Abstinent Participants
Relapse to smoking will be measured through carbon monoxide-verified relapse at weekly study visits among those who abstained during the 3-day quit attempt. Relapse (return to smoking) will be defined as carbon monoxide values (in parts per million) that do not meet abstinence criteria (i.e., 75% reduction from baseline smoking levels).
Time frame: Days 4-56 of the study protocol
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Days to Relapse to Smoking Among Abstinent Participants | 17.0 days | Standard Error 3.45 |
| N-Acetylcysteine (NAC) | Days to Relapse to Smoking Among Abstinent Participants | 3.8 days | Standard Error 1.35 |
Secondary
Number of Participants With 7-day Point Prevalence Abstinence at the 8-week End-of-treatment Visit
Seven day point prevalence abstinence will be measured through biochemical verification via breath carbon monoxide and urinary cotinine analysis. Abstinence is defined as a 75% reduction in carbon monoxide values (parts per million) from smoking baseline levels and a negative urine cotinine measure (\<80 ng/mL).
Time frame: Days 49-56
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With 7-day Point Prevalence Abstinence at the 8-week End-of-treatment Visit | 6 Participants |
| N-Acetylcysteine (NAC) | Number of Participants With 7-day Point Prevalence Abstinence at the 8-week End-of-treatment Visit | 4 Participants |