NCT02874703

Brief Summary

In this study, investigators plan to test two potential mechanisms contributing to diastolic dysfunction among asymptomatic persons with HIV who are on cART. The first proposed mechanism is that heightened systemic immune activation/inflammation in HIV contributes to myocardial inflammation, which in turn promotes myocardial fibrosis. The second mechanism is that ectopic fat deposition (increased visceral adiposity) in HIV relates to increased intramyocardial lipid content, which in turn contributes to diastolic dysfunction. Both HIV positive and HIV-negative participants will undergo cardiac MRI/ MRS imaging studies for evaluation of myocardial fibrosis, myocardial inflammation, and intramyocardial lipid content. Traditional markers of CVD risk, inflammatory markers/immune, hormonal markers, and markers of myocardial stretch/injury will be assessed in relation to cardiac MRI/MRS outcomes. Additionally, a small subset of participants with HIV will undergo longitudinal evaluations to assess effects of a clinically prescribed hormonal therapy on myocardial structure and function.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
48

participants targeted

Target at P25-P50 for all trials

Timeline
Completed

Started Aug 2016

Typical duration for all trials

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

August 1, 2016

Completed
11 days until next milestone

First Submitted

Initial submission to the registry

August 12, 2016

Completed
10 days until next milestone

First Posted

Study publicly available on registry

August 22, 2016

Completed
2.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 1, 2019

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

August 1, 2019

Completed
Last Updated

October 15, 2019

Status Verified

October 1, 2019

Enrollment Period

3 years

First QC Date

August 12, 2016

Last Update Submit

October 11, 2019

Conditions

HIVDiastolic DysfunctionMyocardial Fibrosis

Outcome Measures

Primary Outcomes (1)

  • Extracellular Volume (ECV), a measure of myocardial fibrosis on Cardiac MRI

    3 weeks

Secondary Outcomes (7)

  • Myocardial Inflammation on Cardiac MRI

    3 weeks

  • Intramyocardial fat on Cardiac MRI/MRS

    3 weeks

  • Diastolic function on Cardiac MRI

    3 weeks

  • Visceral Adiposity on MRI

    3 weeks

  • Inflammation/ immune markers

    3 weeks

  • +2 more secondary outcomes

Study Arms (2)

HIV-positive

Other: Cardiac MRI/MRS

HIV-negative

Other: Cardiac MRI/MRS

Interventions

Cardiac MRI/MRSOTHER
HIV-negativeHIV-positive

Eligibility Criteria

Age40 Years - 75 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)
Sampling MethodProbability Sample
Study Population

HIV positive and HIV negative participants

You may qualify if:

  • age ≥40 and ≤75 years
  • documented HIV infection
  • participant report that combination antiretroviral therapy (cART) (any regimen) has been taken stably without \> 4 week interruption for at least 180 days prior to study entry (report of switching regimens in that time frame is permissible)

You may not qualify if:

  • CD4 \< 100 cell/mm3
  • current active AIDS-defining illness
  • current active or recent (not fully resolved within 30 days prior to study entry) systemic bacterial, fungal, parasitic, or viral infections (except HIV, HBV, human papillomavirus \[HPV\], or HCV)
  • current active cancer
  • clinical ASCVD, as defined by 2013 ACC/AHA guidelines (including previous diagnosis of AMI, ACS, stable or unstable angina, coronary or other arterial revascularization, stroke, TIA, PAD), by subject report
  • clinical diagnosis of HFpEF or HFrEF, by subject report
  • diagnosed DM on antihyperglycemic medication
  • current, active use of immune suppressant medication including oral or intravenous corticosteroid or injectable biologic (oral ASA or NSAID use permitted)
  • eGFR \<45 ml/min/1.73 m2 calculated by CDK-EPI
  • standard contraindications to MRI procedure based on MGH MRI Patient Procedure Screening Form - including history of severe allergy to gadolinium
  • use of lipid lowering agents including statin drugs, fibrates, ezetimibe, red yeast rice, niacin or omega-3 fatty acids (\>3 grams/day in standalone formulations) in the 90 days prior to study entry
  • use of ACE inhibitor, ARB, or aldosterone receptor blocker in the 90 days prior to study entry
  • pregnancy or breastfeeding (female subjects of reproductive potential)
  • other medical, psychiatric, or psychological condition that, in the opinion of the study investigator, would interfere with completion of study procedures
  • HIV negative subjects:
  • +14 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Related Publications (6)

  • Toribio M, Awadalla M, Drobni ZD, Quinaglia T, Wang M, Durbin CG, Alagpulinsa DA, Fourman LT, Suero-Abreu GA, Nelson MD, Stanley TL, Longenecker CT, Burdo TH, Neilan TG, Zanni MV. Cardiac strain is lower among women with HIV in relation to monocyte activation. PLoS One. 2022 Dec 30;17(12):e0279913. doi: 10.1371/journal.pone.0279913. eCollection 2022.

    PMID: 36584183DERIVED

  • Masenga SK, Romanelli A, Kooij KW. Plasma osteopontin in persons with HIV and the risk for cardiovascular disease. AIDS. 2023 Feb 1;37(2):355-357. doi: 10.1097/QAD.0000000000003445. No abstract available.

    PMID: 36541647DERIVED

  • Robinson JA, Toribio M, Quinaglia T, Awadalla M, Talathi R, Durbin CG, Alhallak I, Alagpulinsa DA, Fourman LT, Suero-Abreu GA, Nelson MD, Stanley TL, Longenecker CT, Szczepaniak LS, Jerosch-Herold M, Neilan TG, Zanni MV, Burdo TH. Plasma osteopontin relates to myocardial fibrosis and steatosis and to immune activation among women with HIV. AIDS. 2023 Feb 1;37(2):305-310. doi: 10.1097/QAD.0000000000003417. Epub 2022 Nov 3.

    PMID: 36541642DERIVED

  • Toribio M, Fulda ES, Chu SM, Drobni ZD, Awadalla M, Cetlin M, Stanley TL, North CM, Nelson MD, Jerosch-Herold M, Szczepaniak LS, Burdo TH, Looby SE, Neilan TG, Zanni MV. Hot Flashes and Cardiovascular Disease Risk Indices Among Women With HIV. Open Forum Infect Dis. 2021 Jan 12;8(2):ofab011. doi: 10.1093/ofid/ofab011. eCollection 2021 Feb.

    PMID: 33575428DERIVED

  • Toribio M, Awadalla M, Cetlin M, Fulda ES, Stanley TL, Drobni ZD, Szczepaniak LS, Nelson MD, Jerosch-Herold M, Burdo TH, Neilan TG, Zanni MV. Brief Report: Vascular Dysfunction and Monocyte Activation Among Women With HIV. J Acquir Immune Defic Syndr. 2020 Oct 1;85(2):233-238. doi: 10.1097/QAI.0000000000002419.

    PMID: 32541385DERIVED

  • Zanni MV, Awadalla M, Toribio M, Robinson J, Stone LA, Cagliero D, Rokicki A, Mulligan CP, Ho JE, Neilan AM, Siedner MJ, Triant VA, Stanley TL, Szczepaniak LS, Jerosch-Herold M, Nelson MD, Burdo TH, Neilan TG. Immune Correlates of Diffuse Myocardial Fibrosis and Diastolic Dysfunction Among Aging Women With Human Immunodeficiency Virus. J Infect Dis. 2020 Mar 28;221(8):1315-1320. doi: 10.1093/infdis/jiz184.

    PMID: 31100122DERIVED

Biospecimen

Retention: SAMPLES WITHOUT DNA

whole blood, plasma and serum

Study Design

Study Type
observational
Observational Model
CASE CONTROL
Time Perspective
CROSS SECTIONAL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
MD

Study Record Dates

First Submitted

August 12, 2016

First Posted

August 22, 2016

Study Start

August 1, 2016

Primary Completion

August 1, 2019

Study Completion

August 1, 2019

Last Updated

October 15, 2019

Record last verified: 2019-10

Locations

US(1)