Studying Partial-agonists for Ethanol and Tobacco Elimination in Russians With HIV (St PETER HIV)
Condition: HIV Infection; Alcohol Use; Smoking
MeSH terms: Alcohol Drinking
Study type: Interventional
Phase: Phase 2/Phase 3

Summary: 
      This study is a randomized controlled trial (RCT) to compare the effects of varenicline,
      cytisine, and nicotine replacement therapy (NRT) to reduce: 1) alcohol use and craving, 2)
      smoking; and 3) inflammation and risk for coronary heart disease (CHD) and mortality among
      400 HIV-infected Russians, with heavy alcohol consumption and tobacco use.
    

Detailed description: 
      HIV-infected heavy drinking smokers are at high risk for coronary heart disease (CHD) and
      death. The mechanisms driving increased CHD risk in HIV-infected people are unclear, but are
      linked to inflammation. HIV, heavy drinking, and smoking are all pro-inflammatory. HIV viral
      suppression with antiretroviral therapy does not eliminate the elevated CHD risk nor the
      increased inflammation (i.e., pre-HIV infection levels are not restored). Interventions that
      reduce alcohol use, smoking, or both in HIV-infected people could lower inflammation, CHD and
      death risk. Varenicline and cytisine are proven therapies for smoking cessation. When
      compared to placebo, varenicline has higher cessation rates than cytisine. Human trials
      suggest varenicline also has efficacy for reducing alcohol consumption and craving in heavy
      drinking smokers. In murine models, cytisine reduces alcohol consumption. The comparative
      efficacy of varenicline and cytisine to reduce alcohol consumption and by extension,
      inflammation, CHD, and mortality risk, in humans has not been tested, nor has their
      comparative effectiveness been tested for smoking. Neither drug has been tested for smoking
      cessation against nicotine replacement therapy (NRT) in HIV-infected heavy drinking smokers.
      Three compelling reasons to test varenicline and cytisine in HIV-infected heavy drinking
      smokers are: 1) both show promise in HIV-uninfected people; 2) the morbidity caused by heavy
      drinking and smoking in HIV-infected persons is significant; and 3) treating heavy drinking
      and smoking with one medication represents a significant advance in reducing polypharmacy and
      improving patient care. Thus, investigators propose a 4-arm placebo-controlled randomized
      controlled trial (RCT) among 400 HIV-infected heavy drinking smokers. Trial arms are
      varenicline+NRT placebo, cytisine+NRT placebo, NRT+varenicline placebo, NRT+cytisine placebo.
      All participants will receive counseling (alcohol & tobacco) and medications (placebo &
      active). Specific aims will compare effects of varenicline, cytisine, and NRT at 3 months on
      past month % heavy drinking days and alcohol craving, cigarettes per day and smoking
      abstinence (verified by carbon monoxide), inflammation (hsCRP, IL-6), CHD (Reynolds risk
      score), and mortality (VACS index) risk. Investigators hypothesize that (1) Varenicline has
      greater efficacy than NRT for reducing heavy drinking, smoking, inflammation, CHD and
      mortality risk; (2) Cytisine has greater efficacy than NRT; and (3) Varenicline has greater
      efficacy than cytisine for these outcomes. Investigators will conduct an RCT, Studying
      Partial-agonists for Ethanol and Tobacco Elimination in Russians with HIV (St PETER HIV), in
      a country with an HIV epidemic and high per-capita alcohol consumption and smoking.
      Investigators will recruit from the ongoing Russia ARCH cohort in St. Petersburg (part of our
      NIAAA funded HIV/AIDS Alcohol Consortium - URBAN ARCH). If investigator hypotheses are
      correct, St PETER HIV could make nicotinic partial-agonists standard care for HIV+ heavy
      drinking smokers, and lead to reduced inflammation, CHD and mortality risk through this "one
      drug, two diseases" approach. This trial addresses the paucity of RCT data to guide treatment
      of these CHD risk factors in HIV-infected people.

      The Russia ARCH Cohort and the St PETER HIV study will draw from an established cohort of
      HIV-infected smokers and heavy drinkers to compare the effects of two partial nicotinic
      receptors, varenicline and cytisine, on alcohol consumption, alcohol craving, smoking,
      inflammation, CHD risk and mortality risk. St PETER HIV further addresses the paucity of
      randomized controlled trial data to guide treatment of heavy alcohol consumption and smoking
      in HIV-infected people.
    

Intervention name(s): Varenicline; Cytisine; Nicotine Replacement Therapy; Varenicline Placebo; Cytisine Placebo; Nicotine Replacement Therapy Placebo
Intervention type(s): Drug; Drug; Drug; Drug; Drug; Drug
Intervention description(s): 1 week starter kit followed by 1mg twice daily for 12 weeks.; Multi-daily dosing, range 3-9 mg daily for 25 days.; Mouth spray dosing based on standard recommendations tapered over 8 weeks.; 1 week starter kit followed by 1 pill twice daily for 12 weeks.; Multi-daily dosing for 25 days.; Mouth spray dosing based on standard recommendations tapered over 8 weeks.
Intervention MeSH terms: Nicotine; Varenicline
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Alcohol Use; Tobacco Use; Smoking; Inflammation; Coronary Heart Disease; Russia; Varenicline; Cytisine; Nicotine Replacement Therapy; Partial Agonist Therapy; HIV; Reynolds risk score; VACS index