Effect of Heroin Use on Immune Activation and Cardiovascular Risk in HIV

September 28, 2023 updated by: Corrilynn Hileman, MetroHealth Medical Center

The Impact of Intravenous Heroin Use on Immune Activation in Treated HIV

Despite the advent of safer HIV therapies, high levels of markers of systemic inflammation and increased cardiovascular risk threaten the well-being of individuals living with HIV and present a significant challenge for HIV providers. These risks may be accentuated in HIV-infected individuals who are active intravenous drug users (IVDU); however, this population has been specifically excluded from prior studies assessing immune activation and cardiovascular risk in people living with HIV. In this study, the investigators will specifically target HIV-infected participants who are active IVDU, and co-enroll a control group of HIV-infected participants who never used IV drugs. The investigators will study the specific alterations in immune activation and several mechanisms felt to be potential drivers of immune activation outside of the IVDU population, namely gut integrity alteration, microbial translocation, and oxidized lipids. The investigators will also study the effect of IVDU on markers of arterial inflammation and vascular function. Importantly, the investigators will study the reversibility of immune activation, gut dysfunction, and cardiovascular markers after cessation of IVDU, and to that effect, compare strategies for IVDU cessation-buprenorphine/naloxone versus methadone or vivitrol maintenance treatment.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This is a 48-week matched, prospective, observational, cohort study of HIV-infected adults on antiretroviral therapy who actively use heroin or who have never used heroin. The overarching goals are 1) to define the extent and specifics of immune activation in HIV-infected IV heroin users; 2) to define the effect of IV heroin on gut integrity and permeability, and the relationship of gut integrity alteration and immune activation; 3) importantly, to study the reversibility of immune activation, inflammation, and gut dysfunction after cessation of IV heroin, and to that effect, compare strategies for medication assisted treatment-buprenorphine/naloxone versus methadone or vivitrol maintenance; 4) to study if heightened immune activation associated with active intravenous drug use (IVDU) is associated with higher cardiovascular disease risk, including endothelial dysfunction and arterial inflammation, and if these effects are reversible with buprenorphine/naloxone or methadone.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
190

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Ohio
      • Cleveland, Ohio, United States, 44109
        • MetroHealth Medical Center
      • Cleveland, Ohio, United States, 44106
        • University Hospitals Cleveland Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years to 76 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Adults ages 18 to 80 years with and without HIV infection using heroin or initiating treatment for heroin use or not using heroin.

Description

Inclusion Criteria:

  • HIV infection or no HIV infection
  • 18 years or older
  • HIV-1 RNA < 400 if HIV-infected and on antiretroviral therapy
  • On stable antiretroviral therapy at least 12 weeks with cumulative duration of at least a year for HIV-infected if on antiretroviral therapy
  • Currently using heroin at least 1 month with a cumulative duration of at least 12 months in the past for active heroin group
  • Initiating medication assisted treatment for active heroin use initiating medication assisted treatment groups

Exclusion Criteria:

  • Active infection, malignancy or other inflammatory condition
  • Uncontrolled diabetes or hypothyroidism
  • Known cardiovascular disease
  • Pregnancy

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
HIV-infected adults actively using heroin
HIV-infected adults on antiretroviral therapy who are currently using heroin at least 1 month with a cumulative duration of at least 12 months in the past.
Drug: Heroin
This is an observational study. Participants using heroin will be enrolled into this group.
HIV-infected adults never having used heroin
HIV-infected adults on antiretroviral therapy matched to HIV-infected adults actively using heroin by age, sex and CD4+ count.
HIV-infected adults initiating buprenorphine/naloxone
HIV-infected adults on antiretroviral therapy who are currently using heroin at least 1 month with a cumulative duration of at least 12 months in the past initiating medication assisted treatment (MAT) for opioid use disorder with buprenorphine/naloxone.
Drug: buprenorphine/naloxone
This is an observational study. Buprenorphine/naloxone for opioid use disorder will be provided in a standardized way by experienced providers through already established funded treatment programs.
HIV-uninfected adults initiating buprenorphine/naloxone
HIV-uninfected adults who are currently using heroin at least 1 month with a cumulative duration of at least 12 months in the past initiating medication assisted treatment (MAT) for opioid use disorder with buprenorphine/naloxone.
Drug: buprenorphine/naloxone
This is an observational study. Buprenorphine/naloxone for opioid use disorder will be provided in a standardized way by experienced providers through already established funded treatment programs.
HIV-infected adults initiating methadone
HIV-infected adults on antiretroviral therapy who are currently using heroin at least 1 month with a cumulative duration of at least 12 months in the past initiating medication assisted treatment (MAT) for opioid use disorder with methadone
Drug: Methadone
This is an observational study. Methadone for opioid use disorder will be provided in a standardized way by experienced providers through already established funded treatment programs.
HIV-infected adults initiating Vivitrol
HIV-infected adults on antiretroviral therapy who are currently using heroin at least 1 month with a cumulative duration of at least 12 months in the past initiating medication assisted treatment (MAT) for opioid use disorder with Vivitrol.
Drug: Naltrexone Injection
This is an observational study. Naltrexone injection for opioid use disorder will be provided in a standardized way by experienced providers through already established funded treatment programs.
Other Names:
  • Vivitrol
HIV-uninfected adults initiating methadone
HIV-uninfected adults who are currently using heroin at least 1 month with a cumulative duration of at least 12 months in the past initiating medication assisted treatment (MAT) for opioid use disorder with methadone.
Drug: Methadone
This is an observational study. Methadone for opioid use disorder will be provided in a standardized way by experienced providers through already established funded treatment programs.
HIV-uninfected adults initiating Vivitrol
HIV-uninfected adults who are currently using heroin at least 1 month with a cumulative duration of at least 12 months in the past initiating medication assisted treatment (MAT) for opioid use disorder with Vivitrol.
Drug: Naltrexone Injection
This is an observational study. Naltrexone injection for opioid use disorder will be provided in a standardized way by experienced providers through already established funded treatment programs.
Other Names:
  • Vivitrol

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change in plasma soluble CD14 concentration
Time Frame: 48 weeks
soluble marker of monocyte activation
48 weeks
Change in Endopat measure of microvascular function
Time Frame: 48 weeks
Measure of endothelial function
48 weeks
Change in target to background ratio measured by fluorodeoxyglucose (FDG)-positron emission tomography (PET)
Time Frame: 48 weeks
Measure of vascular inflammation
48 weeks
Change in plasma Interferon Gamma-Induced Protein 10 concentration
Time Frame: 48 weeks
soluble marker of inflammation
48 weeks
Change in plasma intestinal fatty acid binding protein concentration
Time Frame: 48 weeks
soluble marker of gut integrity
48 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change in total fat stores measured by Whole body Dual-energy X-ray absorptiometry
Time Frame: 48 weeks
Measurement of fat stores
48 weeks
Change in aortofemoral pulse wave velocity
Time Frame: 48 weeks
Measure of arterial stiffness
48 weeks
Change is waist to hip ratio
Time Frame: 48 weeks
Measurement of central obesity
48 weeks
Change in body mass index
Time Frame: 48 weeks
Body measurement
48 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
MetroHealth Medical Center

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Institute on Drug Abuse (NIDA)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Corrilynn O Hileman, MD, MetroHealth Medical Center
  • Principal Investigator: Grace A McComsey, MD, University Hospitals Cleveland Medical Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 14, 2017

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 31, 2022

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 31, 2022

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 12, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 4, 2019

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 5, 2019

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 2, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 28, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • IRB17-00336 and IRB17-00429
  • 1R01DA044576-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings