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Study of the Effects of Farnesoid X Receptor (FXR) Ligands on the Reactivation of Latent Provirus (FXReservoir)

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ClinicalTrials.gov Identifier: NCT03618862
Recruitment Status : Recruiting
First Posted : August 7, 2018
Last Update Posted : January 8, 2021
Sponsor:
Information provided by (Responsible Party):
Hospices Civils de Lyon

Tracking Information
First Submitted Date August 1, 2018
First Posted Date August 7, 2018
Last Update Posted Date January 8, 2021
Actual Study Start Date January 18, 2019
Estimated Primary Completion Date July 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: August 1, 2018)
Reactivation of latent proviruses [ Time Frame: 1 day ]
The primary endpoint of the study is the presence or absence of reactivation of latent proviruses present in quiescent CD4 + T cells purified from peripheral venous blood following treatment of these cells with Farnesoid X receptor agonists. This is a composite endpoint because the reactivation will be determined qualitatively, virus production or not after treatment, and quantitatively, level of production of infectious and / or defective viruses.
Original Primary Outcome Measures Same as current
Change History
Current Secondary Outcome Measures Not Provided
Original Secondary Outcome Measures Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Study of the Effects of Farnesoid X Receptor (FXR) Ligands on the Reactivation of Latent Provirus
Official Title Study of the Effects of Farnesoid X Receptor (FXR) Ligands on the Reactivation of Latent Provirus in Circulating CD4 + T Cells Isolated From Patients With Undetectable HIV Viremia Under cART
Brief Summary

The Farnesoid X receptor (FXR) is a nuclear receptor that controls the transcription of many genes involved in lipid and glucose metabolism. A recent study opens the hypothesis that Farnesoid X receptor also participates in deoxyribonucleic acid repair mechanisms and possibly in the fight against cell invasion by foreign genomes. This hypothesis implied that modulation of Farnesoid X receptor by ligands could modify Human Immunodeficiency Virus replication. The results of in vitro studies with Human Immunodeficiency Virus-infected cell lines indicate that indeed the modulation of Farnesoid X receptor activity by its ligands induces stimulation of virus production rapidly followed by cell death; the overall effect is therefore antiviral. Farnesoid X receptor ligands have also shown an effect on the reactivation of proviruses in cellular models of viral latency studies. This last data raises the hope of being able to intervene on the reservoir of Human Immunodeficiency Virus.

It is therefore crucial to confirm on quiescent CD4 + T lymphocytes of patients whose viral load is controlled by antiretroviral treatment combining several antiretrovirals the results obtained with the in vitro models.

Providing proof of concept that Farnesoid X receptor agonists can reactivate latent proviruses will open new therapeutic perspectives for attacking the Human Immunodeficiency Virus reservoir with a view to achieving a functional cure for Acquired Immune Deficiency Syndrome. The objective of the study is to confirm ex vivo the data obtained in vitro with cellular models and laboratory viral strains. It is therefore necessary to show that Farnesoid X receptor agonists can reactivate latent viruses or proviruses present in quiescent CD4 + T circulating lymphocytes prepared from venous blood of HIV-positive patients under cART. Human Immunodeficiency Virus-positive patients will be any patients, irrespective of the viral genotype, who initiated antiretroviral therapy, regardless of the combination of antiretrovirals, away from primary infection, when they already had a complete western blot, indicating an evolution of the infection without treatment and constitution of an already evolved reservoir. Patients will have had an undetectable viral load since initiation of treatment with a follow-up of at least one year and will have at least 500 CD4 + T lymphocytes / mm3.

Detailed Description Not Provided
Study Type Observational
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Not Provided
Sampling Method Non-Probability Sample
Study Population human immunodeficiency positive patients under cART.
Condition Hiv
Intervention Biological: Blood sampling
Peripheral venous blood collection of 56 mL during a sampling required by routine monitoring of human immunodeficiency virus infection.
Study Groups/Cohorts Not Provided
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Recruiting
Estimated Enrollment
 (submitted: March 26, 2020)
40
Original Estimated Enrollment
 (submitted: August 1, 2018)
20
Estimated Study Completion Date July 2021
Estimated Primary Completion Date July 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria

Inclusion Criteria:

  • human immunodeficiency virus infected patients
  • T CD4 > 500/mm3. Viral load undetectable for more than a year under stable treatment. No history of virological failure.
  • under first line cART treatment
  • Indetectable viral load

Exclusion Criteria:

  • Acute or chronic anemias.-
  • Acute infections, fever
  • Vaccination in the two months preceding inclusion.
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts
Contact: Tristan FERRY, Pr 04 72 07 11 07 ext +33 tristan.ferry@chu-lyon.fr
Contact: Patrice ANDRE, Pr 04 37 28 23 27 ext +33 patrice.andre@inserm.fr
Listed Location Countries France
Removed Location Countries  
 
Administrative Information
NCT Number NCT03618862
Other Study ID Numbers 69HCL18_0370
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement
Plan to Share IPD: No
Responsible Party Hospices Civils de Lyon
Study Sponsor Hospices Civils de Lyon
Collaborators Not Provided
Investigators Not Provided
PRS Account Hospices Civils de Lyon
Verification Date January 2021