Trial record 5 of 34 for:    " July 24, 2013":" August 23, 2013"[FIRST-RECEIVED-DATE]AND HIV[CONDITION]

IL-23/IL-12 Imbalance and T Lymphocyte Polarization in HIV Infection (INTESTIPAX)

This study is not yet open for participant recruitment.
Verified August 2013 by French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
Sponsor:
Information provided by (Responsible Party):
French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
ClinicalTrials.gov Identifier:
NCT01942655
First received: August 14, 2013
Last updated: September 11, 2013
Last verified: August 2013
  Purpose

Progressive HIV or HIV infection seems to be related to a preferential loss of CD4+ T lymphocytes, especially Th17+, within the mucosal intestinal lymphoid tissue, and with intestinal mucosal damage and bacterial product translocation, which correlates with the hyperactivation of the immune system, therefore with CD4+ T cell loss and prognosis. The objectives of this project are to investigate the correlation between the IL12/IL-23 imbalance and bacterial product translocation, and to study the polarization, infection or depletion of intestinal Th17 ex vivo. The investigators will test the effect of neutralizing anti-IL23 antibodies directed against p40, or less classically, anti- IL-23 p19.


Condition Intervention
HIV Reservoirs
Other: Blood sample and recto-colic biopsies

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: ANRS RF002 Intestipax : Interleukin-23 (IL-23)/Interleukin-12 (IL-12) Imbalance and T Lymphocyte Polarization in HIV Infection

Resource links provided by NLM:


Further study details as provided by French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS):

Primary Outcome Measures:
  • Multiple measures: IL-17 and IL-23 producing cells in blood, and IL-17 and IL-23 coding mRNA in intestinal biopsies. [ Time Frame: 25 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Multiple measures : number of cells producing IL-23 and Th17 cells in intestinal biopsies [ Time Frame: 25 months ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • Multiple measures : HIV viral load levels in blood and intestinal biopsies [ Time Frame: 25 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 45
Study Start Date: October 2013
Estimated Study Completion Date: November 2015
Estimated Primary Completion Date: October 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Patients with recto-colic biopsies prescribed
45 patients
Other: Blood sample and recto-colic biopsies

Detailed Description:

Th17 lymphocytes fight bacterial and fungal intestinal infections. Under combined antiretroviral therapy, even if the plasma viral load is undetectable, hyperactivation can persist, inducing localized replication from reservoirs. In humans, Th17 lymphocyte differentiation and expansion depend on IL-23. The investigators were the first to uncover an imbalance in the respective production of IL-12 and IL-23 in response to Lipopolysaccharide (LPS) in HIV-1 infected patients. IL-23 and its receptor are implicated in the pathogenesis of chronic inflammatory bowel diseases (IBD) like Crohn's disease, where the mucosa is altered by Th17 cells, inducing bacterial product translocation. IBD can be efficiently treated by antibodies directed against Tumor Necrosis Factor-α (TNF-α) or, in current clinical trials, against the p40 chain which is shared by IL-12 and IL-23. Unfortunately, these antibodies inhibit also IL-12. IL-12 is crucial against mycobacteria, which are opportunistic in HIV-infected patients. Antibodies directed against the p19 chain of IL-23 would inhibit Th17 activation more specifically.

The investigators will collect blood and recto-colic biopsies from 15 healthy donors, 15 HIV-infected patients with a viral load higher than 5000 copies/ml and 15 patients with evolutive IBD, to establish a parallel between the two diseases.

The objectives of this project are to study if there is a correlation between the IL12/IL-23 imbalance and bacterial product translocation, and to investigate the polarization, infection or depletion of intestinal Th17 ex vivo. Investigators will test the effect of neutralizing anti-IL23 antibodies directed against p40, or less classically, anti- IL-23 p19.

If these correlations are validated, the investigators will propose anti-IL-23 neutralizing treatment to allow Th17 and intestinal integrity to come back into balance, and therefore to break the vicious cycle of immune system hyperactivation drawn by bacterial translocation.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • Age higher than 18
  • Able to give written consent
  • Recto-colic biopsies prescribed for patient care
  • Covered by French Health Insurance System (Social Security) (15 HIV patients with documented detectable HIV viral load in the past 6 months, 15 HIV negative patients with evolutive IBD, 15 HIV negative patients without evolutive IBD)

Exclusion Criteria:

  • Absence of coverage by French Health insurance system (Social Security)
  • Known progressive malignancy
  • Indeterminate colitis
  • Known autoimmune diseases other than IBD
  • Current chemotherapy or radiotherapy
  • Vulnerable populations (children, pregnant women, persons under legal guardianship, or deprived of freedom by judicial or administrative decision)
  Contacts and Locations
No Contacts or Locations Provided
  More Information

No publications provided

Responsible Party: French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
ClinicalTrials.gov Identifier: NCT01942655     History of Changes
Other Study ID Numbers: ANRS RF002 INTESTIPAX
Study First Received: August 14, 2013
Last Updated: September 11, 2013
Health Authority: France: Agence Nationale de Sécurité du Médicament et des produits de santé

Keywords provided by French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS):
HIV
Chronic inflammatory bowel disease
Reservoirs
IL-17
IL-23
Intestinal biopsies

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases

ClinicalTrials.gov processed this record on April 16, 2014