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Imaging Immune Activation in HIV by PET-MR

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ClinicalTrials.gov Identifier: NCT03684655
Recruitment Status : Recruiting
First Posted : September 26, 2018
Last Update Posted : September 26, 2018
Sponsor:
Collaborator:
National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by (Responsible Party):
Timothy Henrich, University of California, San Francisco

Brief Summary:
This is a single center exploratory imaging study involving one intravenous microdose of [18F]F-AraG followed by whole-body positron emission tomography-magnetic resonance (PET-MR) imaging in HIV infected individuals to determine the anatomical distribution of the PET tracer. Participants will be enrolled if they were treated during early or late HIV infection. In addition, individuals not on antiretroviral therapy (ART) or with HIV-1 plasma RNA levels >5,000 copies/mL will be enrolled.

Condition or disease Intervention/treatment Phase
HIV Infections Drug: [18F]F-AraG (2'-deoxy-2'-fluoro-9-β-D-arabinofuranosylguanine) Phase 1

Detailed Description:

The PET radiofluorinated imaging agent, [18F]F-AraG (2'-deoxy-2'-fluoro-9-β-D-arabinofuranosylguanine; trade name VisAcT) localizes to sites of immune activation and is predominantly accumulated in proliferative T cells. As a result, there is interest in imaging residual immune activation in the setting of both treated and untreated HIV-1 infection, a disease in which chronic immune activation and inflammation may lead to significant morbidity, despite the use of otherwise suppressive ART.

The primary endpoint is to determine the anatomical distribution of [18F]F-AraG in HIV-infected individuals taking or not taking antiretroviral therapy.

Secondary objectives are to determine if [18F]F-AraG PET-MRI is able to detect differences in T cell activation between patients with early versus late treated HIV infection and to determine if [18F]F-AraG uptake correlates with direct blood and tissue measures of HIV reservoir size and activity in the above cohorts/studies.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Intervention Model: Single Group Assignment
Intervention Model Description: Adults with HIV Infection taking or not taking antiretroviral therapy
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: Imaging Immune Activation in HIV Infection
Actual Study Start Date : September 21, 2018
Estimated Primary Completion Date : October 1, 2019
Estimated Study Completion Date : June 1, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: [18F]F-AraG

radiofluorinated imaging agent, [18F]F-AraG (2'-deoxy-2'-fluoro-9-β-D-arabinofuranosylguanine)

Trade name: VisAcT

Drug: [18F]F-AraG (2'-deoxy-2'-fluoro-9-β-D-arabinofuranosylguanine)
[18F]F-AraG is a radiolabeled high affinity substrate for deoxyguanosine kinase (dGK) and a low affinity substrate for deoxycytidine kinase (dCK), which are over-expressed in activated T cells.
Other Name: VisAcT




Primary Outcome Measures :
  1. Anatomical distribution of [18F]F-AraG [ Time Frame: 1-4 hours ]
    Anatomical distribution of [18F]F-AraG in HIV-infected individuals taking or not taking antiretroviral therapy as determined by PET-MR imaging.


Secondary Outcome Measures :
  1. [18F]F-AraG uptake in early and later-treated HIV infection [ Time Frame: 1-4 hours ]
    Determine if [18F]F-AraG PET-MRI is able to detect differences in T cell activation in early versus late treated HIV infection, and between HIV infected and historical HIV-uninfected controls

  2. Correlate [18F]F-AraG uptake with measures of HIV persistence [ Time Frame: 1-2 weeks ]
    Determine if [18F]F-AraG uptake correlates with direct blood and tissue measures of HIV reservoir size and activity in the above cohorts/studies.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age >18 years
  2. Ability to read and understand written informed consent document
  3. HIV infection, and Initiated a combination ART regimen, or, has never received ART, or, has received ART in the past, but has not been taking for a least 1 month prior to enrollment

Exclusion Criteria:

  1. Any contra-indication to MRI, including permanent pacemaker, implantable metallic device/ prosthetic, aneurysm clip, non-removable piercing, or severe claustrophobia
  2. Any medical condition that would compromise the imaging acquisition, in the opinion of the investigator
  3. Patients who are pregnant (female patients of childbearing age will be tested prior to injection of imaging agent - positive test will exclude from participating in the study)
  4. Patients who are breastfeeding
  5. Patients who have had prior allogeneic stem cell or solid organ transplant
  6. Screening absolute neutrophil count <1,000 cells/mm3, platelet count <70,000 cells/mm3, hemoglobin < 8 mg/dL, estimated creatinine clearance <40 mL/minute, aspartate aminotransferase >100 units/L, alanine aminotransferase >100 units/L.
  7. Absolute CD4+ T cell count <100 cells/μL (HIV infected individuals only)
  8. Serious illness requiring hospitalization or parental antibiotics within the preceding 3 months
  9. Current HIV-related opportunistic infection such as pneumocystis pneumonia, disseminated microbacterial infection, invasive cryptococcal disease, candidal esophagitis (limited oral thrush acceptable) and cerebral toxoplasmosis
  10. Previously diagnosed myelodysplasia syndrome. or history of lymphoproliferative disease prior to study entry
  11. History of congestive heart failure as defined by physician documentation in the medical record at any time prior to screening that required medication for heart failure or that required medical management within 1 year prior to study entry
  12. Vaccination within 14 days of study entry

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): NCT03684655


Contacts
Contact: Timothy J Henrich, MD 415-206-5518 timothy.henrich@ucsf.edu

Locations
United States, California
University of California, San Francisco Recruiting
San Francisco, California, United States, 94110
Contact: Timothy J Henrich, MD    415-206-5518    timothy.henrich@ucsf.edu   
Principal Investigator: Timothy J Henrich, MD         
Sub-Investigator: Henry F Vanbrocklin, PhD         
Sub-Investigator: Steven J Deeks, MD         
Sub-Investigator: Benajamin Franc, MD         
Sponsors and Collaborators
University of California, San Francisco
National Institute of Allergy and Infectious Diseases (NIAID)
Investigators
Principal Investigator: Timothy J Henrich, MD University of California, San Francisco

Publications:
Responsible Party: Timothy Henrich, Associate Professor of Medicine, University of California, San Francisco
ClinicalTrials.gov Identifier: NCT03684655     History of Changes
Other Study ID Numbers: 16-20302
First Posted: September 26, 2018    Key Record Dates
Last Update Posted: September 26, 2018
Last Verified: September 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: De-identified individual participant data from primary and secondary outcome measures will be shared.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)
Analytic Code
Time Frame: Data will become available 6 months following study completion.
Access Criteria: Data access requests will be reviewed by the principal investigator and study co-investigators. Requesters will be required to sign a Data Access Agreement.

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Timothy Henrich, University of California, San Francisco:
HIV infection
Positron Emission Tomography
F-AraG
Magnetic Resonance Imaging

Additional relevant MeSH terms:
Infection
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