Correlates and Consequences of Increased Immune Activation in Injection Drug Users

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

Detailed Description
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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.

Official Title
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Correlates and Consequences of Increased Immune Activation in Injection Drug Users

Conditions
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Intravenous Drug Usage

Intervention / Treatment
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* Procedure: Sigmoidoscopy with biopsy


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| heroin injecting drug users<br>Sigmoidoscopy with biopsy, in medically stable active injecting drug users | Procedure: Sigmoidoscopy with biopsy<br>* Sigmoidoscopy with biopsy<br>|
| healthy controls<br>Sigmoidoscopy with biopsy, in non-injecting controls- | Procedure: Sigmoidoscopy with biopsy<br>* Sigmoidoscopy with biopsy<br>|
| Former heroin injection drug users<br>Sigmoidoscopy with biopsy, in former injectors of heroin with or without other agents | Procedure: Sigmoidoscopy with biopsy<br>* Sigmoidoscopy with biopsy<br>|

What is the study measuring?
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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 |