- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03684655
Imaging Immune Activation in HIV by PET-MR
Imaging Immune Activation in HIV Infection
Study Overview
Status
Conditions
Intervention / Treatment
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
Enrollment (Estimated)
Phase
- Phase 1
Contacts and Locations
Study Contact
- Name: Timothy J Henrich, MD
- Phone Number: 415-206-5518
- Email: timothy.henrich@ucsf.edu
Study Locations
-
-
California
-
San Francisco, California, United States, 94110
- Recruiting
- University of California, San Francisco
-
Contact:
- Timothy J Henrich, MD
- Phone Number: 415-206-5518
- Email: timothy.henrich@ucsf.edu
-
Principal Investigator:
- Timothy J Henrich, MD
-
Sub-Investigator:
- Henry F Vanbrocklin, PhD
-
Sub-Investigator:
- Steven J Deeks, MD
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Sub-Investigator:
- Benajamin Franc, MD
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Age >18 years
- Ability to read and understand written informed consent document
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.
(Of note, per Department of Health and Human Services (DHHS) guidelines, the protocol team will strongly recommend that all HIV+ participants initiate ART who not done so already, both for their own health and to prevent the transmission of HIV infection.)
Laboratory evaluations obtained within 60 days prior to entry. i. Platelet count ≥100,000/mm3 ii. ANC >1500/mm3 iii. Aspartate aminotransferase (AST) <2 x ULN iv. Alanine aminotransferase (ALT) <2 x ULN v. CD4+ T cell count >100 cells/mm3 for HIV infected individuals vi. Calculated creatinine clearance (CrCl) ≥60 mL/min as estimated by the Cockcroft-Gault equation: For men, (140 - age in years) x (body weight in kg) ÷ (serum creatinine in mg/dL x 72) = CrCl (mL/min)*
- For women, multiply the result by 0.85 = CrCl (mL/min)
Exclusion Criteria:
- Exclusion criteria will include any contra-indication to MRI, including permanent pacemaker, implantable metallic device/ prosthetic, aneurysm clip, non-removable piercing, or severe claustrophobia
- Any medical condition that would compromise the imaging acquisition, in the opinion of the investigator
- Individuals who have received systemic immune modifying therapy within 60 days of study enrollment (excluding HIV DNA vaccine).
- Participants who are pregnant (female participants of childbearing age will be tested prior to injection of imaging agent at entry visit/initial visit - positive test will exclude from further participation in the study)
- Participants who are breastfeeding
- Female participants of reproductive potential (defined as women who have not been post-menopausal for at least 24 consecutive months (i.e., who have had menses within the preceding 24 months), or women who have not undergone surgical sterilization, specifically hysterectomy and/or bilateral oophorectomy or bilateral salpingectomy) must have a negative urine or serum pregnancy test with a sensitivity of at least 25 mIU/mL performed at the entry/initial visit, and again within 24 hours prior to PET imaging. Females of reproductive potential will need to be on 2 forms of birth control (excluding withdrawal or timing methods).
- Participants who have had prior allogeneic stem cell or solid organ transplant
- Screening absolute neutrophil count <1,500 cells/mm3, platelet count <100,000 cells/mm3, hemoglobin < 8 mg/dL, estimated creatinine clearance <60 mL/minute, aspartate aminotransferase >2 x ULN, alanine aminotransferase >2 x ULN.
- Serious illness requiring hospitalization or parental antibiotics within the preceding 3 months
- Current HIV-related opportunistic infection such as pneumocystis pneumonia, disseminated microbacterial infection, invasive cryptococcal disease, candidal esophagitis (limited oral thrush acceptable) and cerebral toxoplasmosis
- Previously diagnosed myelodysplasia syndrome. or history of lymphoproliferative disease prior to study entry
- 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
- Active Hepatitis C virus (HCV) infection. Prior history of treated HCV infection with sustained virological response will be allowed.
- Active systemic autoimmune diseases.
- Routine clinical vaccination within 14 days of study entry
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Diagnostic
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: [18F]F-AraG
radiofluorinated imaging agent, [18F]F-AraG (2'-deoxy-2'-fluoro-9-β-D-arabinofuranosylguanine) Trade name: VisAcT |
[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 Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
1-4 hours
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
[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
|
1-4 hours
|
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.
|
1-2 weeks
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Timothy J Henrich, MD, University of California, San Francisco
Publications and helpful links
General Publications
- Franc BL, Goth S, MacKenzie J, Li X, Blecha J, Lam T, Jivan S, Hawkins RA, VanBrocklin H. In Vivo PET Imaging of the Activated Immune Environment in a Small Animal Model of Inflammatory Arthritis. Mol Imaging. 2017 Jan 1;16:1536012117712638. doi: 10.1177/1536012117712638.
- Ronald JA, Kim BS, Gowrishankar G, Namavari M, Alam IS, D'Souza A, Nishikii H, Chuang HY, Ilovich O, Lin CF, Reeves R, Shuhendler A, Hoehne A, Chan CT, Baker J, Yaghoubi SS, VanBrocklin HF, Hawkins R, Franc BL, Jivan S, Slater JB, Verdin EF, Gao KT, Benjamin J, Negrin R, Gambhir SS. A PET Imaging Strategy to Visualize Activated T Cells in Acute Graft-versus-Host Disease Elicited by Allogenic Hematopoietic Cell Transplant. Cancer Res. 2017 Jun 1;77(11):2893-2902. doi: 10.1158/0008-5472.CAN-16-2953.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- RNA Virus Infections
- Virus Diseases
- Blood-Borne Infections
- Communicable Diseases
- Sexually Transmitted Diseases, Viral
- Sexually Transmitted Diseases
- Lentivirus Infections
- Retroviridae Infections
- Immunologic Deficiency Syndromes
- Immune System Diseases
- Slow Virus Diseases
- Urogenital Diseases
- Genital Diseases
- HIV Infections
- Infections
- Acquired Immunodeficiency Syndrome
Other Study ID Numbers
- 16-20302
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
IPD Sharing Time Frame
IPD Sharing Access Criteria
IPD Sharing Supporting Information Type
- STUDY_PROTOCOL
- SAP
- ANALYTIC_CODE
- CSR
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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