Nicotine Dependence, Smoking Cessation
Conditions
Keywords
Tobacco Smoking, Smoking Cessation, Nicotine Dependence, Tobacco Use Disorder
Brief summary
The purpose of this study is to evaluate the effects of 12 weeks of varenicline as compared to nicotine replacement therapy for smoking cessation among outpatients in treatment for substance use disorders. The intervention also incorporates counseling (Brief Advice), (adapted for sobriety settings), skills training and medication management.
Detailed description
People with substance use disorders (SUD) have a high prevalence and rate of smoking with little success in quitting, so stronger approaches are needed to encourage attempts to quit smoking. Brief advice (BA), to motivate cessation, produced some benefit but low abstinence rates for smokers with SUDs while adding free transdermal nicotine replacement therapy (NRT) improved short-term cessation rates. Varenicline has been found to produce higher rates of short and long-term abstinence than bupropion or placebo. However, a comparison between the efficacy of varenicline and NRT has not yet conducted with people with SUDs. Given the lack of effectiveness for standard smoking treatments for this population, what needs to be known is whether varenicline would increase the smoking abstinence rates relative to NRT when all receive motivational counseling. The primary aim of this study is to evaluate the effects of 12 weeks of varenicline as compared to NRT, using a two-group randomized placebo-controlled design on smoking cessation rates for 12 months among 274 outpatients in treatment for SUD. The counseling incorporates BA (adapted slightly for sobriety settings by directly addressing barriers and concerns expressed by substance abusers), skills training and medication management. Confirmed point-prevalence and sustained abstinence will be assessed at 3 and 6 a months after the start of treatment. Secondary aims will examine potential mediators of effect including within-treatment abstinence, craving, and nicotine withdrawal levels. The potential significance is to add to knowledge about the most effective ways to maximize smoking cessation among substance abusers, important given that no methods are known to work with this difficult population. No study published to date has compared varenicline to NRT for efficacy with patients with SUD.
Interventions
Nicotine replacement treatment (NRT) will follow the clinical practice guidelines for nicotine patch for people smoking at least 10 cigarettes per day (USDHHS, 2000), modified to allow 12 weeks use (tapering recommended for people with AUDs by Hughes et al., 2003b): 21 mg/day for 4 weeks, 14 mg/day for 4 weeks, 7 mg/day for 4 weeks.
DRUGvarenicline
Varenicline (VAR, 2 mg/d in divided doses) will be administered as follows. VAR: participant takes 0.5 mg/d for the first 3 days, 1 mg/d (0.5 mg 2x/d) for the next 4 days, and 2mg/d (1.0mg 2x/d) for 12 weeks.
The counseling consists of 10 sessions of Brief Advice (BA).BA is a simple smoking cessation counseling strategy: Assess smoking and initial interest in cessation, advise patient to quit smoking, assist patient in quitting, discussion of sobriety specific concerns, and cognitive-behavioral skills training. Medication management is conducted in every session, smoking cessation pamphlets are available. Session 1 (60 min, in-person) will be 1 week before Quit Day.Session 2 (30 min, in-person) takes place on Quit Day. Session 3 (10 min, in-person) will be 1 week later. Sessions 4-10 will be 5-10 min. telephone contacts at Weeks 2, 3, 4, 6, 8, 10, and 12 after Quit Day.
Sponsors
National Institute on Drug Abuse (NIDA)
Brown University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of substance abuse or dependence by DSM-IV criteria * Currently smoking at least 10 cigarettes per day for the past 6 months
Exclusion criteria
* Active psychosis or marked organic impairment according to medical records, or evidence of hallucinations or delusions * Current use of any nicotine replacement, or other smoking cessation treatment * Medical contraindications for NRT (including pregnancy, nursing, women not using birth control during heterosexual sex, history of unstable angina, history of severe congestive heart failure, uncontrolled hypertension, lung cancer, supplemental oxygen, allergy to adhesive, severe skin disease that requires treatment) * Medical contraindications for VAR (including pregnancy, nursing, severe renal impairment by laboratory test, history of intolerance of varenicline, history of serious suicidal ideation or attempts in the past 5 years)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 7-day Point-prevalence Smoking Abstinence | 3 month follow up | 7 -day smoking cessation confirmed by expired alveolar CO levels of \< 10 ppm or salivary cotinine \< 16 ng/ml. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Length of Longest Continuous Abstinence | Weeks 9 to 12 | — |
| Percent Smoking Days | 3 month follow up | — |
| Percent Relapsed to Drug Use | 3 month follow up | — |
| Percent Relapsed to Any Heavy Drinking | 3 month follow up | 6 or more drinks for men; 5 or more drinks for women |
| Beck Depression Inventory | Week 12 | 0-10 = These ups and downs are considered normal 11-16 = Mild mood disturbance 17-20 = Borderline clinical depression 21-30 = Moderate depression 31-40 = Severe depression over 40 = Extreme depression |
Countries
United States
Participant flow
Pre-assignment details
Five individuals enrolled were found to not meet study criteria, 3 did not pass the medical screen, and 13 individuals were lost prior to being randomized.
Participants by arm
| Arm | Count |
|---|---|
| Nicotine Replacement + PLA Pill Nicotine Replacement Treatment (NRT): Nicotine replacement treatment (NRT) will follow the clinical practice guidelines for nicotine patch for people smoking at least 10 cigarettes per day (USDHHS, 2000), modified to allow 12 weeks use (tapering recommended for people with AUDs by Hughes et al., 2003b): 21 mg/day for 4 weeks, 14 mg/day for 4 weeks, 7 mg/day for 4 weeks.
Behavioral counseling for smoking cessation consists of 10 sessions of Brief Advice (BA).BA is a simple smoking cessation counseling strategy: Assess smoking and initial interest in cessation, advise patient to quit smoking, assist patient in quitting, discussion of sobriety specific concerns, and cognitive-behavioral skills training. Medication management is conducted in every session, smoking cessation pamphlets are available. Session 1 (60 min, in-person) will be 1 week before Quit Day.Session 2 (30 min, in-person) takes place on Quit Day. Session 3 | 60 |
| Varenicline + PLA Patch varenicline: Varenicline (VAR, 2 mg/d in divided doses) will be administered as follows. VAR: participant takes 0.5 mg/d for the first 3 days, 1 mg/d (0.5 mg 2x/d) for the next 4 days, and 2mg/d (1.0mg 2x/d) for 12 weeks.
Behavioral counseling for smoking cessation consists of 10 sessions of Brief Advice (BA).BA is a simple smoking cessation counseling strategy: Assess smoking and initial interest in cessation, advise patient to quit smoking, assist patient in quitting, discussion of sobriety specific concerns, and cognitive-behavioral skills training. Medication management is conducted in every session, smoking cessation pamphlets are available. Session 1 (60 min, in-person) will be 1 week before Quit Day.Session 2 (30 min, in-person) takes place on Quit Day. Session 3 (10 min, in-person) will be 1 week later. Sessions 4-10 will be 5-10 min. telephone contacts at Weeks 2, 3, 4, 6, 8, 10, and 12 after Quit Day.
Pl | 77 |
| Total | 137 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 25 | 21 |
| Overall Study | Withdrawal by Subject | 4 | 7 |
Baseline characteristics
| Characteristic | Varenicline + PLA Patch | Total | Nicotine Replacement + PLA Pill |
|---|---|---|---|
| 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 | 77 Participants | 137 Participants | 60 Participants |
| Age, Continuous | 39.96 years STANDARD_DEVIATION 10.51 | 39.6 years STANDARD_DEVIATION 10 | 39.20 years STANDARD_DEVIATION 9.7 |
| Region of Enrollment United States | 77 participants | 137 participants | 60 participants |
| Sex: Female, Male Female | 38 Participants | 65 Participants | 27 Participants |
| Sex: Female, Male Male | 39 Participants | 72 Participants | 33 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 3 / 60 | 1 / 77 |
| serious Total, serious adverse events | 3 / 60 | 10 / 77 |
Outcome results
Primary
7-day Point-prevalence Smoking Abstinence
7 -day smoking cessation confirmed by expired alveolar CO levels of \< 10 ppm or salivary cotinine \< 16 ng/ml.
Time frame: 3 month follow up
Population: Intent to Treat Note: People who were lost were counted as smoked
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nicotine Replacement + PLA Pill | 7-day Point-prevalence Smoking Abstinence | 2 participants |
| Varenicline + PLA Patch | 7-day Point-prevalence Smoking Abstinence | 10 participants |
p-value: <0.0595% CI: [0.91, 20.56]Chi-squared
Primary
7-day Point-prevalence Smoking Abstinence
7 -day smoking cessation confirmed by expired alveolar CO levels of \< 10 ppm or salivary cotinine \< 16 ng/ml.
Time frame: 6 month follow up
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nicotine Replacement + PLA Pill | 7-day Point-prevalence Smoking Abstinence | 2 participants |
| Varenicline + PLA Patch | 7-day Point-prevalence Smoking Abstinence | 7 participants |
p-value: 0.395% CI: [0.58, 14.5]Fisher Exact
Secondary
Beck Depression Inventory
0-10 = These ups and downs are considered normal 11-16 = Mild mood disturbance 17-20 = Borderline clinical depression 21-30 = Moderate depression 31-40 = Severe depression over 40 = Extreme depression
Time frame: Week 12
Population: Outcome data available for 80 participants who had valid depression data 12 week assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nicotine Replacement + PLA Pill | Beck Depression Inventory | 5.19 units on a scale | Standard Deviation 6.53 |
| Varenicline + PLA Patch | Beck Depression Inventory | 5.75 units on a scale | Standard Deviation 8.47 |
p-value: 0.7595% CI: [-3.98, 2.87]t-test, 2 sided
Secondary
Length of Longest Continuous Abstinence
Time frame: Weeks 9 to 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nicotine Replacement + PLA Pill | Length of Longest Continuous Abstinence | 6.25 Days | Standard Deviation 10.06 |
| Varenicline + PLA Patch | Length of Longest Continuous Abstinence | 7.84 Days | Standard Deviation 11.39 |
p-value: 0.595% CI: [-6.29, 3.11]t-test, 2 sided
Secondary
Percent Relapsed to Any Heavy Drinking
6 or more drinks for men; 5 or more drinks for women
Time frame: 6 month follow up
Population: Outcome data available for 80 participants who completed 6 month follow up.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nicotine Replacement + PLA Pill | Percent Relapsed to Any Heavy Drinking | 9 percentage of particpiants |
| Varenicline + PLA Patch | Percent Relapsed to Any Heavy Drinking | 8 percentage of particpiants |
p-value: 0.18Chi-squared
Secondary
Percent Relapsed to Any Heavy Drinking
6 or more drinks for men; 5 or more drinks for women
Time frame: 3 month follow up
Population: Outcome data available for 89 participants who completed 3 month follow up.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nicotine Replacement + PLA Pill | Percent Relapsed to Any Heavy Drinking | 7 percentage of participants |
| Varenicline + PLA Patch | Percent Relapsed to Any Heavy Drinking | 9 percentage of participants |
p-value: 0.72Chi-squared
Secondary
Percent Relapsed to Drug Use
Time frame: 3 month follow up
Population: Outcome data available for 89 participants who completed 3 month follow up.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nicotine Replacement + PLA Pill | Percent Relapsed to Drug Use | 12 percentage of participants |
| Varenicline + PLA Patch | Percent Relapsed to Drug Use | 14 percentage of participants |
p-value: 0.57Chi-squared
Secondary
Percent Relapsed to Drug Use
Time frame: 6 month follow up
Population: Outcome data available for 80 participants who completed 6 month follow up.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nicotine Replacement + PLA Pill | Percent Relapsed to Drug Use | 8 percentage of participants |
| Varenicline + PLA Patch | Percent Relapsed to Drug Use | 18 percentage of participants |
p-value: 0.31Chi-squared
Secondary
Percent Smoking Days
Time frame: 3 month follow up
Population: Outcome data available for 89 participants who completed 3 month follow up.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nicotine Replacement + PLA Pill | Percent Smoking Days | 62.39 percentage of days | Standard Deviation 38.84 |
| Varenicline + PLA Patch | Percent Smoking Days | 70.37 percentage of days | Standard Deviation 38.79 |
p-value: 0.3495% CI: [-24.64, 8.68]t-test, 2 sided
Secondary
Percent Smoking Days
Time frame: 6 month follow up
Population: Outcome data available for 80 participants who completed 6 month follow up.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nicotine Replacement + PLA Pill | Percent Smoking Days | 84.52 percentage of days | Standard Deviation 31.25 |
| Varenicline + PLA Patch | Percent Smoking Days | 77.12 percentage of days | Standard Deviation 37.61 |
p-value: 0.3695% CI: [-8.73, 23.52]t-test, 2 sided