This study, based in India, is testing the efficacy of varenicline to help smokeless tobacco users with cessation efforts.

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.

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.

12 weeks

Sample size and reduced power; lack of long-term assessments; a priori inclusion of covariates in prediction models; adherence to medication was low.