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Sequential Analysis Before and After Treatment Initiation to Unravel the Role of Naturally Occurring Extracellular Vesicles in HIV Infection (Saturne-HIV)

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ClinicalTrials.gov Identifier: NCT04653610
Recruitment Status : Recruiting
First Posted : December 4, 2020
Last Update Posted : January 24, 2022
Sponsor:
Information provided by (Responsible Party):
University Hospital, Ghent

Brief Summary:
This study aims to evaluate the role of extracellular vesicles in HIV-infection, by determining the expression profile and content of EVs before and after treatment initiation in HIV-infected patients, through extensive blood and tissue sampling (leukapheresis, stool sampling and colon biopsies). A one-time sampling (blood, stool, colon biopsies) will also be performed in HIV-seronegative healthy volunteers to confirm that results found in HIV-infected patients are related to the disease.

Condition or disease
Hiv

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Study Type : Observational
Estimated Enrollment : 66 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Sequential Analysis Before and After Treatment Initiation to Unravel the Role of Naturally Occurring Extracellular Vesicles in HIV Infection
Actual Study Start Date : January 27, 2021
Estimated Primary Completion Date : January 2023
Estimated Study Completion Date : January 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Group/Cohort
HIV-infected individuals
HIV-seronegative healthy volunteers



Primary Outcome Measures :
  1. Extracellular Vesicles analysis-NTA [ Time Frame: 4 years ]
    Extracellular vesicles (EV) will be isolated through a combination of size-exclusion chromatography (SEC) and Optiprep density gradient (ODG). Nanoparticle Tracking Analysis (NTA) will be performed to obtain the concentration and size distribution of EVs in the samples.

  2. Extracellular Vesicles analysis-microscopy [ Time Frame: 4 years ]
    The isolated EVs will be further visualized by (electron) microscopy.

  3. Extracellular Vesicles analysis-western blot [ Time Frame: 4 years ]
    The isolated EVs will be further characterized through western blot.

  4. Extracellular Vesicles analysis-PCR [ Time Frame: 4 years ]
    The isolated EVs will be further characterized through PCR.

  5. Extracellular Vesicles analysis-proteomics [ Time Frame: 4 years ]
    The isolated EVs will be further characterized through proteomic analysis.

  6. Extracellular Vesicles analysis-RNAsequencing [ Time Frame: 4 years ]
    The isolated EVs will be further characterized through RNA sequencing.

  7. Extracellular Vesicles analysis-reporter assays [ Time Frame: 4 years ]
    Reporter assays will be performed to quantitatively measure bacterial EV-associated lipopolysaccharide (LPS).

  8. Quantification of HIV DNA and RNA [ Time Frame: 4 years ]
    Digital PCR

  9. Immunological analysis-FACS [ Time Frame: 4 years ]
    Immunophenotyping by flow cytometric assays will be performed of different cells to assess the phenotype of innate immune cells, using FACS analysis.

  10. Immunological analysis-ELISA [ Time Frame: 4 years ]
    Immunophenotyping by flow cytometric assays will be performed of different cells to assess the phenotype of innate immune cells, using ELISA.

  11. Gene expression analysis/transcriptomics [ Time Frame: 4 years ]
  12. Microbiome monitoring [ Time Frame: 4 years ]
    Gut microbiome will be analyzed in stool and colon biopsies using next-generation sequencing (NGS) of rRNA gene amplicons to identify bacteria at genus/species level

  13. Virological analysis-FLIPS [ Time Frame: 4 years ]
    HIV will be characterized by Full Length Individual Proviral Sequencing (FLIPS).

  14. Virological analysis-integration site [ Time Frame: 4 years ]
    HIV will be characterized by integration site analysis.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Our aim is to enroll a minimum of 32 and a maximum of 50 untreated HIV-infected patients. We aim to include a minimum of 16 patients with a CD4 T cell count lower than 350 cells/µl and a minimum of 16 patients with a CD4 T cell count higher than 350 cells/µl. Furthermore we aim to include 16 HIV-seronegative healthy donors to confirm that the results found in HIV-patients are related to the disease.
Criteria

A. HIV-infected individuals

A.1. Inclusion Criteria:

  • Documented untreated HIV-1 infection defined as followed: HIV-1-specific antibody+(western blot); p31+ (ELISA)
  • CD4 T cell count will be determined standard of care (SOC). A minimum of 16 patients will be included with a CD4 T cell count lower than 350 cells/µl and a minimum of 16 patients with a CD4 T cell count higher than 350 cells/µl
  • Able and willing to provide written informed consent
  • Age ≥ 18 years and ≤ 65 years
  • Ability to attend the complete schedule of assessments and patient visits as described in the schedule below
  • Ability and willingness to have blood, stool and colon samples collected and stored for 20 years after finalizing the study, and used for various research purposes

A.2. Exclusion Criteria:

  • Recent HIV-infection, early diagnosis
  • Previous or current history of opportunistic infection (AIDS defining events as defined in category C of the CDC clinical classification), consisting of chronic HIV-1 infection
  • Evidence of active HBV infection (Hepatitis B surface antigen positive or HBV viral load positive in the past and no evidence of subsequent seroconversion (=HBV antigen or viral load negative and positive HBV surface antibody))
  • Evidence of active HCV infection: HCV antibody positive result within 60 days prior to study entry with positive HCV viral load or, if the HCV antibody result is negative, a positive HCV RNA result within 60 days prior to study entry
  • Current or known history of cardiomyopathy or significant ischemic or cerebrovascular disease
  • Current or known history of cancer
  • Pregnancy or breastfeeding
  • Any conditions, including preexisting psychiatric and psychological disorders, which will in the opinion of the investigator interfere with the trial conduct or safety of the participant. An initial psychiatric assessment will be made by the treating physician. Since making a correct psychological assessment at the time of diagnosis can be difficult, a visit with a psychologist is planned for patients included in the study, for a second evaluation. This will be planned within the first month after diagnosis. In consultation with the psychologist, further sampling will be planned or the patient will be excluded from further sampling.
  • Previous participation in a trial evaluating an immune modulating agent
  • Abnormal laboratory tests results at screening:

    1. Confirmed hemoglobin <11g/dl for women and <12 g/dl for men
    2. Confirmed platelet count < 100 000/µl
    3. Confirmed neutrophil count <1000/μl
    4. Confirmed AST and/or ALT > 10x ULN
  • Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements
  • Acute or serious illness, in the opinion of the site investigator, requiring systemic treatment and/or hospitalization within 60 days prior to entry
  • Known inflammatory bowel disease (Crohn's disease or ulcerative colitis)

B. Healthy Volunteers

B.1. Inclusion Criteria:

  • Able and willing to provide written informed consent
  • Age ≥ 18 years and ≤ 65 years
  • Ability to attend the complete sampling schedule, as described below
  • Ability and willingness to have blood, stool and colon samples collected and stored for 20 years and used for various research purposes

B.2. Exclusion Criteria:

  • HIV-infection
  • Evidence of active HBV infection (Hepatitis B surface antigen positive or HBV viral load positive in the past and no evidence of subsequent seroconversion (=HBV antigen or viral load negative and positive HBV surface antibody))
  • Evidence of active HCV infection: HCV antibody positive result within 60 days prior to study entry with positive HCV viral load or, if the HCV antibody result is negative, a positive HCV RNA result within 60 days prior to study entry
  • Current or known history of cardiomyopathy or significant ischemic or cerebrovascular disease
  • Current or known history of cancer
  • Pregnancy or breastfeeding
  • Any conditions, including preexisting psychiatric and psychological disorders, which will in the opinion of the investigator interfere with the trial conduct or safety of the participant
  • Previous participation in a trial evaluating an immune modulating agent
  • Abnormal laboratory tests results at screening:

    1. Confirmed hemoglobin <11g/dl for women and <12 g/dl for men
    2. Confirmed platelet count < 100 000/µl
    3. Confirmed neutrophil count <1000/μl
    4. Confirmed AST and/or ALT > 10xULN
  • Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements
  • Acute or serious illness, in the opinion of the site investigator, requiring systemic treatment and/or hospitalization within 60 days prior to entry
  • Known inflammatory bowel disease (Crohn's disease or ulcerative colitis)

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): NCT04653610


Contacts
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Contact: Linos Vandekerckhove, Prof. Dr. +3293323398 linos.vandekerckhove@ugent.be

Locations
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Belgium
Ghent University Hospital Recruiting
Ghent, Oost-Vlaanderen, Belgium, 9000
Contact: Linos Vandekerckhove, Prof. Dr.    +3293323398    linos.vandekerckhove@ugent.be   
Sponsors and Collaborators
University Hospital, Ghent
Investigators
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Principal Investigator: Linos Vandekerckhove, Prof. Dr. University Hospital, Ghent
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Responsible Party: University Hospital, Ghent
ClinicalTrials.gov Identifier: NCT04653610    
Other Study ID Numbers: BC-08408
First Posted: December 4, 2020    Key Record Dates
Last Update Posted: January 24, 2022
Last Verified: January 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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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 University Hospital, Ghent:
HIV
Extracellular Vesicles
Additional relevant MeSH terms:
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HIV Infections
Infections
Blood-Borne Infections
Communicable Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Immunologic Deficiency Syndromes
Immune System Diseases