PET/CT Imaging Companion Study To ACTG A5314

Summary

HIV-infected individuals on antiretroviral therapy (ART) are at increased risk for cardiovascular disease (CVD), likely due to chronically increased inflammation. Low-dose methotrexate (LDMTX) may reduce CVD risk in people with rheumatoid arthritis, who like those with HIV, have increased levels of inflammation. The NHLBI is funding a clinical trial targeting the excess inflammation in HIV. That "Parent Study" is a randomized, double-blind, placebo-controlled trial (NCT01949116) that will assess whether 24-week treatment with LDMTX: i) is safe, ii) reduces circulating inflammatory biomarkers and levels of immune cell activation and iii) improves brachial artery reactivity. However, neither the biomarkers nor endothelial function tests measured as part of the parent study will report on atherosclerotic inflammation, (the desired pathobiological target of LDMTX therapy in HIV). As such, the direct evaluation of arterial inflammation would substantially enhance the scientific value of the trial. In this imaging sub-study, the overall goal is to determine if treating virologically suppressed, HIV-infected individuals with LDMTX will reduce inflammation within the arterial wall.

This fully integrated ancillary study would, in a subset of patients enrolled in the parent trial: (i) assess the impact of LDMTX on arterial inflammation, (ii) evaluate mechanisms responsible for arterial inflammation in HIV and iii) explore mechanisms responsible for actions of LDMTX on the artery wall. Accordingly, the proposed study would provide unique and highly complementary information that would greatly increase the knowledge and mechanistic insights gained from Parent Study. The ancillary study has two specific aims1) To determine the impact of anti-inflammatory treatment with LDMTX on arterial inflammation, as assessed by FDG-PET/CT imaging, in virally suppressed HIV-infected individuals., and 2) To evaluate the cellular and biochemical basis of the effect of LDMTX therapy on arterial inflammation in HIV.

Conditions

• HIV
• Inflammation
• Atherosclerosis

Interventions

DRUG

Folic Acid

1 mg folic acid once daily

DRUG

Placebo

placebo once weekly

DRUG

Low Dose Methotrexate

An anti-inflammatory drug

Sponsors & Collaborators

• Brigham and Women's Hospital

  collaborator OTHER

• Harvard School of Public Health (HSPH)

  collaborator OTHER

• University of California, San Francisco

  collaborator OTHER

• Massachusetts General Hospital

  lead OTHER

Principal Investigators

• Ahmed Tawakol, MD · Massachusetts General Hospital and Harvard Medical School

Eligibility

Min Age

40 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2014-11-30

Primary Completion

2016-12-08

Completion

2016-12-08

Countries

• United States

Study Locations