Correlates and Consequences of Increased Immune Activation in Injection Drug Users

The goal of this study is to learn how injection drug use may affect the immune system.

Study Overview

• Status: Completed
• Conditions: Intravenous Drug Usage
• Intervention / Treatment: Procedure: Sigmoidoscopy with biopsy

Detailed Description

The goal of this study is to learn how injection drug use may affect the immune system. One way to measure this is by looking at the blood and the gut, or gastrointestinal tract at the same time. It is thought that activating the immune system by injection drug use may increase destruction of immune cells in the gut. To test this theory, the investigators are enrolling HIV-negative injection drug users, HIV-negative people who do not use drugs and HIV-negative former injection drug users.

• Study Type: Observational
• Enrollment (Actual): 201

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10065
      • The Rockfeller University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Group 1: HIV-uninfected, active IDU defined as a minimum of 3 injections of heroin per week (N=48)

Group 2: Non-injecting controls defined as no lifetime use of injection drugs and no illicit non-injection opiate or cocaine for at least 3 years (N=48)

Group 3: Former injectors of heroin with/without other agents will be recruited and followed after approximately 1 month (N=48) and 3 months (N=48) from the time of last injection.

All groups will be matched for age, sex, and race/ethnicity. Groups 1 and 3 will be matched for Hepatitis C status and HCV RNA levels. Group 1 subjects will be studied twice; at baseline, at 1-2 months to assess stability of findings. Group 2 will be studied once; Group 3 will be studied at 1 and 3 months after ceasing injections.

Description

Inclusion Criteria:

• Ability to give informed consent
• Between the ages of 18 and 55
• Absence of medical conditions that would preclude flexible sigmoidoscopy
• Absence of active opportunistic infection requiring active therapy including antibiotics or anti-neoplastics (note this does not include prophylactic antibiotic therapy)

Exclusion Criteria:

• History of bleeding disorder
• Platelet count below 70,000
• INR>1.5 or PTT>2X control
• Active use of anticoagulants or aspirin therapy that cannot be interrupted
• Comorbid diagnosis of inflammatory bowel disease
• Pregnancy, incarceration, mentally disabled individuals
• HIV-1 infection
• Currently on Hepatitis C treatment

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
heroin injecting drug users; Sigmoidoscopy with biopsy, in medically stable active injecting drug users	Procedure: Sigmoidoscopy with biopsy; Sigmoidoscopy with biopsy
healthy controls; Sigmoidoscopy with biopsy, in non-injecting controls-	Procedure: Sigmoidoscopy with biopsy; Sigmoidoscopy with biopsy
Former heroin injection drug users; Sigmoidoscopy with biopsy, in former injectors of heroin with or without other agents	Procedure: Sigmoidoscopy with biopsy; Sigmoidoscopy with biopsy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Examine the behavioral and immunological correlates of increased immune activation in active and former injection drug users (IDUs) in blood and tissue.	Detailed assessments of blood and GI tissue including measurements of HCV viremia in 1) active HIV-1-uninfected IDUs (N=48) 2) a cohort of individuals entering or in drug treatment programs who have stopped injecting for approximately 1 and 3 months (N=48), the majority of whom we anticipate will be infected with HCV; and 3) non-injecting controls (N=48). In addition to obtaining blood and tissue, we will collect behavioral data including injection and other drug use and sexual behaviors.	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determine the mechanisms of increased immune activation associated with active IDU using a systems biology approach.	This study will isolate specific cell populations from the peripheral blood as well as the GALT that mediate innate and adaptive immune responses. We will perform transcriptional profiling with the goal of identifying gene expression patterns of a-priori defined biological pathways and functional categories that associate with phenotypes of interest. Finally to complement and clarify the results of our in vivo studies, we will examine the in vitro effects of adding morphine and methadone and withdrawing opiates on T cell subsets of interest using a systems biology approach.	3 months

Collaborators and Investigators

• Sponsor: Rockefeller University
• Investigators: Principal Investigator: Martin Markowitz, MD, Aaron Diamond AIDS Research Center

Publications and helpful links

General Publications

• Markowitz M, Deren S, Cleland C, La Mar M, Silva E, Batista P, St Bernard L, Gettie N, Rodriguez K, Evering TH, Lee H, Mehandru S. Chronic Hepatitis C Virus Infection and the Proinflammatory Effects of Injection Drug Use. J Infect Dis. 2016 Nov 1;214(9):1376-1382. doi: 10.1093/infdis/jiw373. Epub 2016 Aug 11.

Study record dates

Study Major Dates

• Study Start: December 1, 2012
• Primary Completion (Actual): September 1, 2014
• Study Completion (Actual): September 1, 2014

Study Registration Dates

• First Submitted: February 28, 2013
• First Submitted That Met QC Criteria: April 9, 2013
• First Posted (Estimate): April 15, 2013

Study Record Updates

• Last Update Posted (Estimate): November 6, 2014
• Last Update Submitted That Met QC Criteria: November 4, 2014
• Last Verified: November 1, 2014

More Information

Terms related to this study

• Other Study ID Numbers: MMA-0774