Tobacco Use Disorder
Conditions
Keywords
nicotine smokeless tobacco chewing tobacco varenicline
Brief summary
This study, based in India, is testing the efficacy of varenicline to help smokeless tobacco users with cessation efforts.
Detailed description
The prevalence of smokeless tobacco use in the United States is low vs. cigarette smoking, yet rates have remained constant over the past few years. In contrast, the rate of smokeless tobacco use in India is 20%. Smokeless tobacco is a carcinogenic and responsible for \ 10,000 deaths/year from oral cancer in India. Unfortunately, there have been remarkably few intervention trials in India for smokeless tobacco users. To date, no trial has evaluated the new FDA approved medication, varenicline, for smokeless tobacco use. We will conduct a randomized placebo-controlled trial of varenicline for smokeless tobacco dependence at the National Drug Dependence Treatment Center (NDDTC) at the All India Institute of Medicine (AIIMS) in New Delhi with 237 smokeless tobacco users. The primary aims of this trial are to: 1) enhance research capacity at the NDDTC (i.e., train AIIMS staff to implement the behavioral counseling protocol with pharmacotherapy, data collection and management procedures); 2) assess the efficacy of varenicline for increasing biochemically confirmed 7-day point prevalence smokeless tobacco quit rates at the end-of treatment; and 3) assess longitudinal patterns of relapse and recovery following treatment with varenicline. The results of this trial may guide future investments to evaluate the efficacy of varenicline for smokeless tobacco dependence in the US, which is critical since smokeless tobacco use in the US may increase in the coming years and no approved pharmacotherapy for this drug dependence exists in the US or around the globe.
Interventions
DRUGVarenicline
Participants will be randomized to receive varenicline or placebo for 12 weeks. The dosing regimen consistent with FDA guidelines will be used: Day 1-Day 3 (0.5mg once daily); Day 4-Day 7 (0.5mg twice daily); and Day 8-Day 84 (1.0mg twice daily).
BEHAVIORALCounseling
All participants will be provided with a structured behavioral counseling program, involving 6 counseling sessions by a trained NDDTC counselor. This will be a manual-based intervention and revised as needed for cultural relevance and sensitivity by Dr. Stigler. The intervention is designed to enhance awareness of the harmful effects of smokeless tobacco, assist the person in developing skills to quit and avoid relapse, and instruct the smokeless tobacco user on medication adherence, as recommended by experts in the field.
Sponsors
All India Institute of Medical Sciences
University of Pennsylvania
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 No maximum
Healthy volunteers
Yes
Inclusion criteria
* males and females * over age 18 * used smokeless tobacco every day for the past year (confirmed with urinary cotinine) * residing within 100km of New Dehli for the next 4 months * interested in quitting use of smokeless tobacco.
Exclusion criteria
* currently enrolled or plan to enroll in another tobacco cessation program in the next 4 months * plan to use other smoking cessation treatments in the next 4 months * smoke cigarettes * have current substance abuse (e.g., opioids, cocaine, marijuana) verified by urine drug screen * have current (last 6-months) alcohol consumption that exceeds 25 standard drinks/week (if past abuse, must be symptom free for ≥ the past 12 months) * Current use or discontinuation within last 14 days of: 1. smoking cessation medications (bupropion, Varenicline, NRT); 2. antipsychotics, atypicals, mood-stabilizers, anti-depressants (tricyclics, SSRIs, MAOIs), anti-panic agents, anti-obsessive agents, anti-anxiety agents, stimulants; 3. Anti-coagulants; 4. Daily medication for asthma or diabetes (eligible with physician approval); * are pregnant, planning a pregnancy, or lactating * have a history or current diagnosis of psychosis, general anxiety disorder,bipolar disorder, or schizophrenia * have a current diagnosis of depression (if past diagnosis, must be symptom free for ≥ the past 12 months) * have an allergy to Varenicline * ever contemplated or attempted suicide * have serious/unstable disease within the past 6 months (e.g., cancer \[but melanoma\], heart disease, HIV/AIDS) * have a history of epilepsy or seizure disorder * have a history or diagnosis within the last 6 months of abnormal rhythms and/or tachycardia (\>100 beats/minute) * have a history or current diagnosis of COPD; cardiovascular disease (stroke, angina); heart attack in the last 6 months; and/or uncontrolled hypertension (SBP\>150 or DBP\>90)16) * have a history of kidney or liver failure * have any medical condition or medication that could compromise safety as determined by a study physician * cannot provide informed consent or complete the study tasks as determined by the Principal Investigator or study physician.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 7-day Point Prevalence Smokeless Tobacco Abstinence Biochemically Confirmed With Urine Cotinine at the End of 12 Weeks of Treatment. | At the end of treatment (12 weeks) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Nicotine Withdrawal and Craving, Negative Affect, Positive Affect, and Side Effects. | Ongoing throughout the treatment period (Baseline to the end of treatment, 12 weeks) | Side Effects |
Countries
India
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Varenicline Varenicline: Participants will be randomized to receive varenicline or placebo for 12 weeks. The dosing regimen consistent with FDA guidelines will be used: Day 1-Day 3 (0.5mg once daily); Day 4-Day 7 (0.5mg twice daily); and Day 8-Day 84 (1.0mg twice daily).
Counseling: All participants will be provided with a structured behavioral counseling program, involving 6 counseling sessions by a trained NDDTC counselor. This will be a manual-based intervention and revised as needed for cultural relevance and sensitivity by Dr. Stigler. The intervention is designed to enhance awareness of the harmful effects of smokeless tobacco, assist the person in developing skills to quit and avoid relapse, and instruct the smokeless tobacco user on medication adherence, as recommended by experts in the field. | 119 |
| Placebo Counseling: All participants will be provided with a structured behavioral counseling program, involving 6 counseling sessions by a trained NDDTC counselor. This will be a manual-based intervention and revised as needed for cultural relevance and sensitivity by Dr. Stigler. The intervention is designed to enhance awareness of the harmful effects of smokeless tobacco, assist the person in developing skills to quit and avoid relapse, and instruct the smokeless tobacco user on medication adherence, as recommended by experts in the field. | 118 |
| Total | 237 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 31 | 33 |
Baseline characteristics
| Characteristic | Varenicline | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 33.8 years STANDARD_DEVIATION 8.4 | 34.7 years STANDARD_DEVIATION 9.9 | 34.2 years STANDARD_DEVIATION 9.2 |
| Sex: Female, Male Female | 3 Participants | 4 Participants | 7 Participants |
| Sex: Female, Male Male | 116 Participants | 114 Participants | 230 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 30 / 119 | 28 / 118 |
| serious Total, serious adverse events | 0 / 119 | 0 / 118 |
Outcome results
Primary
7-day Point Prevalence Smokeless Tobacco Abstinence Biochemically Confirmed With Urine Cotinine at the End of 12 Weeks of Treatment.
Time frame: At the end of treatment (12 weeks)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Varenicline | 7-day Point Prevalence Smokeless Tobacco Abstinence Biochemically Confirmed With Urine Cotinine at the End of 12 Weeks of Treatment. | 30 participants |
| Placebo | 7-day Point Prevalence Smokeless Tobacco Abstinence Biochemically Confirmed With Urine Cotinine at the End of 12 Weeks of Treatment. | 23 participants |
Secondary
Nicotine Withdrawal and Craving, Negative Affect, Positive Affect, and Side Effects.
Side Effects
Time frame: Ongoing throughout the treatment period (Baseline to the end of treatment, 12 weeks)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Varenicline | Nicotine Withdrawal and Craving, Negative Affect, Positive Affect, and Side Effects. | sleep problems | 8 participants |
| Varenicline | Nicotine Withdrawal and Craving, Negative Affect, Positive Affect, and Side Effects. | gastrointestinal problems | 8 participants |
| Placebo | Nicotine Withdrawal and Craving, Negative Affect, Positive Affect, and Side Effects. | sleep problems | 11 participants |
| Placebo | Nicotine Withdrawal and Craving, Negative Affect, Positive Affect, and Side Effects. | gastrointestinal problems | 9 participants |