Ignite Creation Date:
2024-05-06 @ 2:53 PM
Last Modification Date:
2024-10-26 @ 1:39 PM
Study NCT ID:
NCT04451980
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2024-03-26
First Post:
2020-06-16
Brief Title:
The HIV Adipose Tissue Immunology and Metabolism Study
Sponsor:
Vanderbilt University Medical Center
Organization:
Vanderbilt University Medical Center
Study Overview
Official Title:
The HIV Adipose Tissue Immunology and Metabolism Study
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2024-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
HATIM
Brief Summary:
With the introduction of effective anti-retroviral therapy ART HIV-infected persons can now survive for decades but this success has been accompanied by an increased risk of developing metabolic disease and diabetes in HIV-infected persons compared to the general population Recent studies from HIV-negative subjects have identified several associations between circulating immune cell populations and impaired glucose tolerance including increased activated CD4 and CD8 T cells and reduced regulatory T cells Of note these same changes in peripheral T cell subsets are frequently observed in patients with chronic HIV infection The goal of this study is to assess whether the circulating T cell distribution is reflective of the adipose tissue T cell distribution and to understand whether chronic adipose tissue T cell activation may impair adipocyte ie fat cell function and insulin sensitivity If the investigators hypotheses are correct this will demonstrate that chronic peripheral immune activation ie high memory T cells low naïve cells and increased expression of activation surface markers is associated with greater adipose-resident CD4 and CD8 T cell expression of activation markers adipose tissue inflammation and insulin resistance
Detailed Description:
With the introduction of effective antiretroviral therapy ART HIV-infected persons can now survive for decades but this success has been accompanied by an increased risk of developing metabolic disease compared HIV-negative persons In the Multicenter AIDS Cohort Study HIV-infected men had a greater than 4-fold increased incidence of a new diabetes diagnosis compared to HIV-negative men after adjusting for age and body mass index BMI Prevalence studies of diabetes in HIV-infected individuals on ART have reported incidence rates of 31 to 14 per 1000 patient-years Furthermore treated HIV infection appears to act synergistically with other risk factors and diabetes prevalence is especially high among HIV-infected individuals with high BMI and advanced age
Recent studies from HIV-negative subjects identified several associations between adaptive immune cell populations and impaired glucose tolerance Peripheral T regulatory Treg cells are significantly lower in patients with type-2 diabetes while the numbers activated T cells CD4 TH1 pro-inflammatory cells and memory CD4 T cells are higher in diabetics
Immune cells translocate from the circulation into adipose tissue in a dynamic process and T cells are present in the stromal fraction of adipose tissue and affect adipocyte function The striking increase in adipose tissue CD4 TH1 cells and CD8 T cells and a decrease in Treg cells observed in obesity may have an important role in the development of insulin resistance Secretion of the proinflammatory cytokines interferon-γ and interleukin IL-17 by TH1 and TH17 cells are implicated in the induction of proinflammatory M1 macrophages which express IL-6 and tumor necrosis factor alpha and inhibit adipocyte insulin signaling by promoting phosphorylation of insulin receptor substrate 1 The investigators hypothesize that the chronic HIV-related activation of circulating CD4 and CD8 T cells may be accompanied by the accumulation of activated T cells in adipose tissue with adverse effects on metabolic activity
In this study the investigators will test the hypothesis that the oligoclonal expansion of chronically activated peripheral T cells in adipose tissue is a primary driver of macrophage inflammation and reduced adipocyte insulin sensitivity Furthermore the investigators propose that this represents a central mechanistic linkage underlying the association between circulating T cell activation and incident diabetes risk observed in HIV-infected and HIV-negative individuals
Recent studies from HIV-negative subjects identified several associations between adaptive immune cell populations and impaired glucose tolerance Peripheral T regulatory Treg cells are significantly lower in patients with type-2 diabetes while the numbers activated T cells CD4 TH1 pro-inflammatory cells and memory CD4 T cells are higher in diabetics
Immune cells translocate from the circulation into adipose tissue in a dynamic process and T cells are present in the stromal fraction of adipose tissue and affect adipocyte function The striking increase in adipose tissue CD4 TH1 cells and CD8 T cells and a decrease in Treg cells observed in obesity may have an important role in the development of insulin resistance Secretion of the proinflammatory cytokines interferon-γ and interleukin IL-17 by TH1 and TH17 cells are implicated in the induction of proinflammatory M1 macrophages which express IL-6 and tumor necrosis factor alpha and inhibit adipocyte insulin signaling by promoting phosphorylation of insulin receptor substrate 1 The investigators hypothesize that the chronic HIV-related activation of circulating CD4 and CD8 T cells may be accompanied by the accumulation of activated T cells in adipose tissue with adverse effects on metabolic activity
In this study the investigators will test the hypothesis that the oligoclonal expansion of chronically activated peripheral T cells in adipose tissue is a primary driver of macrophage inflammation and reduced adipocyte insulin sensitivity Furthermore the investigators propose that this represents a central mechanistic linkage underlying the association between circulating T cell activation and incident diabetes risk observed in HIV-infected and HIV-negative individuals
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None