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Selection of Farnesoid X Receptor (FXR) Ligands on the Reactivation of Latent HIV Proviruses (FXR#2)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT05219916
Recruitment Status : Terminated (It is unlikely that the scientific question will ever be answered. Thus, it would be considered unethical to continue the trial.)
First Posted : February 2, 2022
Last Update Posted : March 13, 2023
Information provided by (Responsible Party):
Hospices Civils de Lyon

Brief Summary:

The FXReservoir#1 study (NCT03618862) showed that certain FXR ligands reactivate latent viruses in the reservoir circulating in all HIV+ patients tested. These molecules appear as latency reversal agents (LRA) of silent viruses of the HIV reservoir. They can be part of the strategy to eradicate this reservoir, responsible for recurrences of the infection when combined anti-retroviral treatments are stopped.

Two effective leads have been identified on in vitro tests and on ex vivo reactivation using FXReservoir#1. These molecules come from a chemical library of FXR ligands developed by the Inserm team behind the discovery of a role for FXR in viral infections.

A first series of optimized molecules derived from these leads has been synthesized; these molecules, after screening on viral and ADMET (Absorption, Distribution, Metabolisme, Excretion and Toxicity) in vitro tests, must be tested ex vivo on CD4+ lymphocytes from the circulating peripheral reservoir of HIV+ patients in order to select the best molecules with LRA activity. This step is essential before considering the clinical development of an LRA.

Condition or disease Intervention/treatment Phase
Human Immunodeficiency Virus I Infection Procedure: Blood collection. Not Applicable

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 17 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: Descriptive physiopathological study
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Selection of Farnesoid X Receptor (FXR) Ligands as Latency Reversal Agents (LRA) of Latent HIV Proviruses in Circulating CD4+ T Lymphocytes Isolated From Patients With Undetectable HIV Viremia Under cART (Combined Antiretroviral Treatments)
Actual Study Start Date : April 12, 2022
Actual Primary Completion Date : July 22, 2022
Actual Study Completion Date : July 22, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arm Intervention/treatment
Experimental: Adult patients infected by HIV, controlled under treatment.
Blood sample collection from HIV controlled patients during their scheduled consultation, after obtaining their non-opposition by an investigator.
Procedure: Blood collection.

One additional 80 mL blood collection will be collected from HIV patients during a scheduled blood collection as part of their regular follow-up.

Samples will be transported within 3-5 hours by a carrier approved for the transportation of infectious biological samples from the Croix Rousse hospital to the P3 laboratory of the Ecole Normale Supérieure, Lyon for analysis.

Primary Outcome Measures :
  1. Measurement of the reactivation level and the EC50 of the optimized molecules. [ Time Frame: At inclusion. ]

    Measurement of reactivation level compared to that obtained with the reference LRA Ingenol, and EC50 of molecules derived from active leads and preselected on viral and ADMET criteria in vitro to allow the choice of the best molecule for future clinical development.

    PBMCs (peripheral blood mononuclear cells) and rCD4+Tcells will be isolated and treated with the test molecules for 3 days. The treated cells will be incubated to determine the number of cells producing HIV/ million of rCD4+ T cells. FXR ligands will be used at 10 µM. Dose-response assay will be carried out to determine the EC50 (half maximal effective concentration) of the active molecules and the best molecules in the final selection will be tested in combination with inhibitors of the metabolic pathway to confirm their specificity of action.

    Molecules derived from the 2 leads will be screened in successive series.

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Criteria relating to the population studied: patients aged 18 to 65 years old, men or women, regardless of ethnic origin.
  • Nosological criteria: HIV-1 infection, documented by a complete western blot and/or a detectable viral load at the time of diagnosis, regardless of the viral subtype.
  • Pathology severity and progression criteria: patients with a CD4+ count greater than 500 elements/mm3 at the last follow-up visit prior to inclusion in the study. Undetectable viral load for at least six months on stable treatment.
  • Criteria relating to treatments/strategies/procedures: Current cART treatment mandatory, regardless of the combination of anti-retrovirals, effective with undetectable viral load. The number of processing lines is not limited.
  • Criteria relating to regulation: Absence of opposition

Exclusion Criteria:

  • Criteria relating to the population studied: pregnant or breastfeeding women
  • Criteria relating to contraindications to the protocol explorations:

Acute or chronic anaemias Acute infections, fever Coagulation disorders, patients taking anticoagulants

- Criteria relating to regulation: Subjects placed under judicial safeguard, guardianship or curatorship Subjects participating in another research with an ongoing exclusion period.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05219916

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Service des maladies infectieuses et tropicales Hôpital de la Croix Rousse
Lyon, France, 69004
Sponsors and Collaborators
Hospices Civils de Lyon
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Principal Investigator: Tristan FERRY, MD-PhD Service des maladies infectieuses et tropicales, Hôpital de la Croix Rousse, Hospices Civils de Lyon
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Responsible Party: Hospices Civils de Lyon
ClinicalTrials.gov Identifier: NCT05219916    
Other Study ID Numbers: 69HCL21_0846
First Posted: February 2, 2022    Key Record Dates
Last Update Posted: March 13, 2023
Last Verified: March 2023

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Hospices Civils de Lyon:
Additional relevant MeSH terms:
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Acquired Immunodeficiency Syndrome
HIV Infections
Immunologic Deficiency Syndromes
Immune System Diseases
Blood-Borne Infections
Communicable Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Slow Virus Diseases
Genital Diseases
Urogenital Diseases