Clinical trial NCT02797587: Studying Partial-agonists for Ethanol and Tobacco Elimination in Russians With HIV (St PETER HIV)
Official title: URBAN ARCH 4/5 Russia Cohort-Targeting HIV-comorbidities With Pharmacotherapy to Reduce Alcohol and Tobacco Use in HIV-infected Russians
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: HIV Infection
Alcohol Use
Smoking
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
Lead sponsor: Boston Medical Center
Sponsor class: OTHER
Collaborators: name: National Institute on Alcohol Abuse and Alcoholism (NIAAA)
First posted: 2016-06-13
Enrollment: 400
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Eligibility criteria: Inclusion Criteria:

* 18-70 years old
* HIV-infected
* ≥ 5 heavy drinking days in the past 30 days (NIAAA at-risk drinking levels)
* Smoking an average of at least 5 cigarettes per day
* Provision of contact information for 2 contacts to assist with follow-up
* Stable address within 100 kilometers
* Possession of a telephone (home or cell)
* Interest in cutting down/quitting alcohol or tobacco
* Able and willing to comply with all study protocols and procedures

Exclusion Criteria:

* Not fluent in Russian
* Cognitive impairment
* Pregnant or planning to become pregnant in next 3 months
* Breastfeeding
* Unstable psychiatric illness (i.e. ,answered yes to any of the following: past three month a) active hallucinations; b) mental health symptoms prompting a visit to the ED or hospital; mental health medication changes due to worsening symptoms; presence of suicidal ideations)
* History of pheochromocytoma
* Taking smoking cessation medications in past 30 days
* History of seizures
* History of Buerger's disease
* Acute coronary syndrome within 1 month of enrollment
* Systolic BP \> 180 mm Hg or diastolic BP \> 105 mm Hg
* Currently taking anti-tuberculosis medications
* Currently taking Galantamine or Physostigmine
* BAC level of 0.10% or higher
* Known allergy to varenicline (Chantix) or cytisine (Tabex)

Primary outcomes:
measure: Percent heavy drinking days in past 30 days
timeFrame: Participants will be followed for up to 12 months (primary endpoint at 3 month)
Secondary outcomes:
measure: Alcohol craving
timeFrame: Participants will be followed for up to 12 months (primary endpoint at 3 month)
measure: Carbon monoxide-validated smoking cessation
timeFrame: Participants will be followed for up to 12 months (primary endpoint at 3 month)
measure: Coronary heart disease risk
timeFrame: Participants will be followed for up to 12 months (primary endpoint at 3 month)
measure: Mortality risk
timeFrame: Participants will be followed for up to 12 months (primary endpoint at 3 month)
measure: Cigarettes per day in past 7 days
timeFrame: Participants will be followed for up to 12 months (primary endpoint at 3 month)
measure: hsCRP levels
timeFrame: Participants will be followed for up to 12 months (primary endpoint at 3 month)
measure: IL-6 levels
timeFrame: Participants will be followed for up to 12 months (primary endpoint at 3 month)
Other outcomes:
Locations:
city: St. Petersburg
country: Russian Federation
facility: First St. Petersburg Pavlov State Medical University
Study officials:
affiliation: Boston University/Boston Medical Center
name: Jeffrey H Samet, MA, MA, MPH
role: PRINCIPAL_INVESTIGATOR
References:
citation: Tindle HA, Freiberg MS, Cheng DM, Gnatienko N, Blokhina E, Yaroslavtseva T, Bendiks S, Patts G, Hahn J, So-Armah K, Stein MD, Bryant K, Lioznov D, Krupitsky E, Samet JH. Effectiveness of Varenicline and Cytisine for Alcohol Use Reduction Among People With HIV and Substance Use: A Randomized Clinical Trial. JAMA Netw Open. 2022 Aug 1;5(8):e2225129. doi: 10.1001/jamanetworkopen.2022.25129.