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

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ClinicalTrials.gov Identifier: NCT02797587
Recruitment Status : Recruiting
First Posted : June 13, 2016
Last Update Posted : May 30, 2019
Sponsor:
Collaborator:
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Information provided by (Responsible Party):
Jeffrey Samet, Boston Medical Center

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.

Condition or disease Intervention/treatment Phase
HIV Infection Alcohol Use Smoking Drug: Varenicline Drug: Cytisine Drug: Nicotine Replacement Therapy Drug: Varenicline Placebo Drug: Cytisine Placebo Drug: Nicotine Replacement Therapy Placebo Phase 2 Phase 3

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 400 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: URBAN ARCH 4/5 Russia Cohort-Targeting HIV-comorbidities With Pharmacotherapy to Reduce Alcohol and Tobacco Use in HIV-infected Russians
Actual Study Start Date : July 19, 2017
Estimated Primary Completion Date : April 2020
Estimated Study Completion Date : December 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Alcohol HIV/AIDS

Arm Intervention/treatment
Active Comparator: Varenicline + Nicotine Replacement Therapy placebo
Study participants will receive active varenicline and be instructed to take the medication for 12 weeks; participants will also receive a placebo Nicotine Replacement Therapy mouth spray for 8 weeks.
Drug: Varenicline
1 week starter kit followed by 1mg twice daily for 12 weeks.

Drug: Nicotine Replacement Therapy Placebo
Mouth spray dosing based on standard recommendations tapered over 8 weeks.

Placebo Comparator: Varenicline placebo + Nicotine Replacement Therapy
Study participants will receive placebo varenicline and be instructed to take the placebo medication for 12 weeks; participants will also receive an active Nicotine Replacement Therapy mouth spray for 8 weeks.
Drug: Nicotine Replacement Therapy
Mouth spray dosing based on standard recommendations tapered over 8 weeks.

Drug: Varenicline Placebo
1 week starter kit followed by 1 pill twice daily for 12 weeks.

Active Comparator: Cytisine + Nicotine Replacement Therapy placebo
Study participants will receive active cytisine and be instructed to take the medication for 25 days; participants will also receive a placebo Nicotine Replacement Therapy mouth spray for 8 weeks.
Drug: Cytisine
Multi-daily dosing, range 3-9 mg daily for 25 days.

Drug: Nicotine Replacement Therapy Placebo
Mouth spray dosing based on standard recommendations tapered over 8 weeks.

Placebo Comparator: Cytisine placebo + Nicotine Replacement Therapy
Study participants will receive placebo cytisine and be instructed to take the medication for 25 days; participants will also receive an active Nicotine Replacement Therapy mouth spray for 8 weeks.
Drug: Nicotine Replacement Therapy
Mouth spray dosing based on standard recommendations tapered over 8 weeks.

Drug: Cytisine Placebo
Multi-daily dosing for 25 days.




Primary Outcome Measures :
  1. Percent heavy drinking days in past 30 days [ Time Frame: Participants will be followed for up to 12 months (primary endpoint at 3 month) ]
    Self-reported past 30-day alcohol consumption obtained via the Timeline Followback (TLFB) method, heavy drinking defined by NIAAA definition


Secondary Outcome Measures :
  1. Alcohol craving [ Time Frame: Participants will be followed for up to 12 months (primary endpoint at 3 month) ]
    Measured by the Penn Alcohol Craving Scale

  2. Carbon monoxide-validated smoking cessation [ Time Frame: Participants will be followed for up to 12 months (primary endpoint at 3 month) ]
    Self-reported 7-day point prevalence abstinence and a carbon monoxide measured in end-expired air threshold of <10 ppm.

  3. Coronary heart disease risk [ Time Frame: Participants will be followed for up to 12 months (primary endpoint at 3 month) ]
    Measured by the Reynolds risk score

  4. Mortality risk [ Time Frame: Participants will be followed for up to 12 months (primary endpoint at 3 month) ]
    Measured by the VACS index

  5. Cigarettes per day in past 7 days [ Time Frame: Participants will be followed for up to 12 months (primary endpoint at 3 month) ]
    Self-report, obtained via Timeline Followback (TLFB) method

  6. hsCRP levels [ Time Frame: Participants will be followed for up to 12 months (primary endpoint at 3 month) ]
    Biomarker of inflammation measured via study test

  7. IL-6 levels [ Time Frame: Participants will be followed for up to 12 months (primary endpoint at 3 month) ]
    Biomarker of inflammation measured via study test



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02797587


Contacts
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Contact: Jeffrey H Samet, MD, MA, MPH 617-414-7444 jsamet@bu.edu
Contact: Matthew S Freiberg, MD, MSc 615-875-9729 matthew.s.freiberg@vanderbilt.edu

Locations
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Russian Federation
First St. Petersburg Pavlov State Medical University Recruiting
St. Petersburg, Russian Federation, 197022
Contact: Evgeny Krupitsky, MD,PhD,DMdSc    +7-812-365-2217    kruenator@gmail.com   
Sponsors and Collaborators
Boston Medical Center
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Investigators
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Principal Investigator: Jeffrey H Samet, MA, MA, MPH Boston University/Boston Medical Center

Additional Information:
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Responsible Party: Jeffrey Samet, Chief, Section of General and Internal Medicine, Boston Medical Center
ClinicalTrials.gov Identifier: NCT02797587     History of Changes
Other Study ID Numbers: H-35288
U01AA020780 ( U.S. NIH Grant/Contract )
First Posted: June 13, 2016    Key Record Dates
Last Update Posted: May 30, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: All data from the study will be placed into the URBAN ARCH repository.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Jeffrey Samet, Boston Medical Center:
Cytisine
Alcohol Use
Tobacco Use
Smoking
Inflammation
Coronary Heart Disease
Russia
Varenicline
Nicotine Replacement Therapy
Partial Agonist Therapy
HIV
Reynolds risk score
VACS index
Additional relevant MeSH terms:
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Alcohol Drinking
Drinking Behavior
Nicotine
Varenicline
Ganglionic Stimulants
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Nicotinic Agonists
Cholinergic Agonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action