Studying Partial-agonists for Ethanol and Tobacco Elimination in Russians With HIV (St PETER HIV)

Smoking Clinical Trial

— 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02797587
• Other study ID #: H-35288
• Secondary ID: U01AA020780
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: July 19, 2017
• Est. completion date: December 15, 2020

Study information

• Verified date: December 2020
• Source: Boston Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 400
• Est. completion date: December 15, 2020
• Est. primary completion date: April 30, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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)

Related Conditions & MeSH terms

• Alcohol Drinking
• Alcohol Use
• HIV Infection
• Smoking

Intervention

Drug:
• Varenicline
1 week starter kit followed by 1mg twice daily for 12 weeks.
• Cytisine
Multi-daily dosing, range 3-9 mg daily for 25 days.
• Nicotine Replacement Therapy
Mouth spray dosing based on standard recommendations tapered over 8 weeks.
• Varenicline Placebo
1 week starter kit followed by 1 pill twice daily for 12 weeks.
• Cytisine Placebo
Multi-daily dosing for 25 days.
• Nicotine Replacement Therapy Placebo
Mouth spray dosing based on standard recommendations tapered over 8 weeks.

Locations

Country	Name	City	State
Russian Federation	First St. Petersburg Pavlov State Medical University	St. Petersburg

Sponsors (2)

Lead Sponsor	Collaborator
Boston Medical Center	National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Country where clinical trial is conducted

Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent heavy drinking days in past 30 days	Self-reported past 30-day alcohol consumption obtained via the Timeline Followback (TLFB) method, heavy drinking defined by NIAAA definition	Participants will be followed for up to 12 months (primary endpoint at 3 month)
Secondary	Alcohol craving	Measured by the Penn Alcohol Craving Scale	Participants will be followed for up to 12 months (primary endpoint at 3 month)
Secondary	Carbon monoxide-validated smoking cessation	Self-reported 7-day point prevalence abstinence and a carbon monoxide measured in end-expired air threshold of <10 ppm.	Participants will be followed for up to 12 months (primary endpoint at 3 month)
Secondary	Coronary heart disease risk	Measured by the Reynolds risk score	Participants will be followed for up to 12 months (primary endpoint at 3 month)
Secondary	Mortality risk	Measured by the VACS index	Participants will be followed for up to 12 months (primary endpoint at 3 month)
Secondary	Cigarettes per day in past 7 days	Self-report, obtained via Timeline Followback (TLFB) method	Participants will be followed for up to 12 months (primary endpoint at 3 month)
Secondary	hsCRP levels	Biomarker of inflammation measured via study test	Participants will be followed for up to 12 months (primary endpoint at 3 month)
Secondary	IL-6 levels	Biomarker of inflammation measured via study test	Participants will be followed for up to 12 months (primary endpoint at 3 month)

External Links

•   URBAN ARCH, a member of NIAAA CHAART (Consortiums for HIV/AIDS & Alcohol Research Translation) initiative, conducts and disseminates interdisciplinary research on how alcohol impacts people with HIV and develops interventions to reduce related outcomes.