Use of 99mTc Tilmanocept for Imaging Arterial Inflammation

The purpose of this study is to measure arterial 99mTc-Tilmanocept uptake using single photon emission computed tomography (SPECT/CT) scanning in HIV infected subjects known to have subclinical coronary atherosclerosis as assessed by contrast-enhanced coronary computed tomography angiography (CCTA).

Study Overview

• Status: Completed
• Conditions: HIV
• Intervention / Treatment: Other: Arterial Imaging

Detailed Description

Detailed Description:

Patients with HIV have been shown to have increased atherosclerotic risk compared to age-matched controls, and this risk is thought to be related to increased systemic immune activation. Specifically, systemic immune activation may contribute to destabilizing coronary atherosclerotic plaque, leading to plaque rupture and myocardial infarction. This study is intended to measure arterial uptake of the macrophage specific marker 99mTc-Tilmanocept using single photon emission computed tomography, applied initially to a group of HIV-infected patients with known subclinical coronary atherosclerosis on CCTA. Moreover, traditional markers of CVD risk and inflammatory markers will be assessed in relation to CV imaging outcomes. Positive findings in the index HIV group with known subclinical atherosclerosis will prompt subsequent study of three comparison groups, as above.

• Study Type: Observational
• Enrollment (Actual): 30

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

HIV-infected subjects and HIV non-infected subjects

Description

HIV infected subjects with known subclinical atherosclerosis:

Inclusion criteria:

• men and women, ages 18+, with documented HIV infection
• current use of antiretroviral therapy (ART), with no changes to regimen within last 3 months
• history of subclinical atherosclerosis on CCTA

Exclusion criteria:

• pregnancy or breastfeeding
• known active opportunistic infection requiring ongoing medical therapy (not including Hepatitis B/C)
• CD4 count < 50 cells/mm3
• history of angina, myocardial infarction, acute coronary syndrome, or coronary artery stenting or surgery
• recent and/or current treatment with prescription, systemic steroids or anti-inflammatory/immune suppressant medical therapies
• current use of statin or use of statin for > 1 month within the last 6 months
• known allergy to dextrans and/or DPTA and/or radiometals and/or iodinated contrast media
• eGFR < 60 ml/min/1.73 m2 calculated by CDK-EPI
• contraindications to beta blockers or nitroglycerin
• significant radiation exposure (>2 CT angiograms) received within the past 12 months
• BMI > 35 kg/m2 or waist circumference > 70 cm (scanner limitations)

HIV infected subjects without known subclinical atherosclerosis:

Inclusion criteria:

• men and women, ages 18+, with documented HIV infection
• current use of antiretroviral therapy (ART), with no changes to regimen within last 3 months
• history of clean aorta/ coronaries on CCTA

Exclusion criteria:

- Same as exclusion criteria for HIV infected subjects with known subclinical atherosclerosis

HIV negative subjects with known subclinical atherosclerosis:

Inclusion criteria:

• men and women, ages 18+, without documented HIV infection
• history of subclinical atherosclerosis on CCTA

Exclusion criteria:

• pregnancy or breastfeeding
• history of angina, myocardial infarction, acute coronary syndrome, or coronary artery stenting or surgery
• recent and/or current treatment with prescription, systemic steroids or anti-inflammatory/immune suppressant medical therapies
• current use of statin or use of statin for > 1 month within the last 6 months
• known allergy to dextrans and/or DPTA and/or radiometals and/or iodinated contrast media
• eGFR < 60 ml/min/1.73 m2 calculated by CDK-EPI
• contraindications to beta blockers or nitroglycerin
• significant radiation exposure (>2 CT angiograms) received within the past 12 months
• BMI > 35 kg/m2 or waist circumference > 70 cm (scanner limitations)

HIV negative subjects without known subclinical atherosclerosis:

Inclusion criteria:

• men and women, ages 18+, without documented HIV infection
• history of clean aorta/coronaries on CCTA

Exclusion criteria:

- Same as exclusion criteria for HIV negative subjects with known subclinical atherosclerosis

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
HIV infected with known subclinical atherosclerosis	Other: Arterial Imaging
HIV infected without known subclinical atherosclerosis	Other: Arterial Imaging
Non-HIV infected with known subclinical atherosclerosis	Other: Arterial Imaging
Non-HIV infected without known subclinical atherosclerosis	Other: Arterial Imaging

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Aortic 99mTc-Tilmanocept uptake on SPECT/CT scanning in HIV Patients	within 6 weeks of screening visit

Secondary Outcome Measures

Outcome Measure	Time Frame
Aortic plaque burden and morphology on CCTA in HIV Patients	within 6 weeks of screening visit
Traditional markers of cardiovascular disease (CVD) risk and inflammatory markers in relation to cardiovascular imaging outcomes	within 6 weeks of screening visit
Imaging assessments in the coronary vasculature in HIV patients	within 6 weeks of screening visit
Comparison of imaging assessments b/ HIV patients w/ known subclinical atherosclerosis, HIV patients w/o known subclinical atherosclerosis, non HIV patients w/ known subclinical atherosclerosis and non HIV patients w/o known subclinical atherosclerosis	within 6 weeks of screening visit
99mTc-Tilmanocept uptake on SPECT/CT in regions other than the aorta	within 6 weeks of screening visit

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Collaborators: Navidea Biopharmaceuticals; Havard University Center for AIDS Research
• Investigators: Principal Investigator: Steven Grinspoon, M.D., Massachusetts General hospital

Publications and helpful links

General Publications

• Toribio M, Wilks MQ, Hedgire S, Lu MT, Cetlin M, Wang M, Alhallak I, Durbin CG, White KS, Wallis Z, Schnittman SR, Stanley TL, El-Fakhri G, Lee H, Autissier P, Zanni MV, Williams KC, Grinspoon SK. Increased Macrophage-Specific Arterial Infiltration Relates to Noncalcified Plaque and Systemic Immune Activation in People With Human Immunodeficiency Virus. J Infect Dis. 2022 Nov 11;226(10):1823-1833. doi: 10.1093/infdis/jiac301.
• Zanni MV, Toribio M, Wilks MQ, Lu MT, Burdo TH, Walker J, Autissier P, Foldyna B, Stone L, Martin A, Cope F, Abbruzzese B, Brady T, Hoffmann U, Williams KC, El-Fakhri G, Grinspoon SK. Application of a Novel CD206+ Macrophage-Specific Arterial Imaging Strategy in HIV-Infected Individuals. J Infect Dis. 2017 Apr 15;215(8):1264-1269. doi: 10.1093/infdis/jix095.

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2015
• Primary Completion (Actual): August 1, 2021
• Study Completion (Actual): August 1, 2021

Study Registration Dates

• First Submitted: August 26, 2015
• First Submitted That Met QC Criteria: September 4, 2015
• First Posted (Estimate): September 7, 2015

Study Record Updates

• Last Update Posted (Actual): April 6, 2022
• Last Update Submitted That Met QC Criteria: April 4, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: HIV; Atherosclerosis; Tilmanocept
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Vasculitis; Inflammation; Arteritis
• Other Study ID Numbers: 2014P001832

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No