Ferumoxytol-enhanced Imaging and Mapping in neuroAIDS

AIDS Dementia Complex Clinical Trial

Official title:

Ferumoxytol-enhanced Imaging and Quantitative Susceptibility Mapping in neuroAIDS

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02678767
• Other study ID #: 2013-077
• Secondary ID: H0321R21NS087951
• Status: Completed
• Phase: Phase 2
• First received: February 2, 2016
• Last updated: October 25, 2017
• Start date: February 2015
• Est. completion date: September 2017

Study information

• Verified date: October 2017
• Source: University of Hawaii
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This project will investigate the ability of a novel MRI contrast agent to identify and quantitate ongoing monocyte/macrophage (M/MΦ)-mediated inflammation in the brains of HIV-infected individuals.

Description:

HIV-associated neurocognitive disorders (HAND) continue to be prevalent despite effective combination antiretroviral therapy (cART) and have a significant impact on morbidity and quality of life. Monocytes/macrophages (M/MΦ) are believed to play a critical role in the pathogenesis of HAND. Neuroimaging HIV research has not focused on assessing M/MΦ-mediated inflammation in the brain. Currently, no neuroimaging modality exists that can define the extent of active inflammation due to M/MΦ in HAND either as a clinical diagnostic tool or to assist in defining objective improvement in clinical trials addressing HAND. Ferumoxytol is an ultra-small iron oxide MRI contrast agent avidly taken up by circulating M/MΦ. The investigators hypothesize that ferumoxytol-based imaging can identify ongoing inflammation due to perivascular M/MΦ which is believed to represent a key pathologic correlate of HAND.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: September 2017
• Est. primary completion date: September 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 40 Years to 65 Years

Eligibility

Inclusion Criteria:

• Age 40-65 years

• Plasma HIV RNA < 48 copies/ml (HIV+ subjects only)

• On stable cART >= 1 year (HIV+ subjects only)

• Global neuropsychological (NP) score <-0.5 in at least one cognitive domain known to be affected by HIV (neurocognitively impaired subjects only)

• Documentation of negative HIV infection by an FDA approved test (HIV- subjects only)

Exclusion Criteria:

• Active substance use

• History of myocardial infarct or stroke

• Diabetes

• Chronic hepatitis C virus (HCV) infection

• Uncontrolled major affective disorder, active psychosis, central nervous system disease that affects the brain structure, or other uncontrolled chronic medical condition that in the opinion of the investigator may impact NP testing or the study outcome

• Psychoactive or other medications which may impact NP testing

• Factors that preclude MRI

• Known hypersensitivity to ferumoxytol

• History of laboratory measurements consistent with an iron overload syndrome

• Medical conditions that require frequent blood transfusions

• Taking oral iron supplements

• Elevated iron levels

• Any condition, which in the opinion of the investigator, would compromise the subject's ability to participate

• Multiple drug allergies that may pose a greater risk of anaphylaxis associated with ferumoxytol

• Pregnant, unwillingness to practice birth control, or breastfeeding

• Unable to give informed consent

Related Conditions & MeSH terms

• AIDS Dementia Complex
• Dementia

Intervention

Drug:
• Ferumoxytol
All subjects will receive neurocognitive testing. Subjects will have a brain MRI prior to drug infusion. A one-time ferumoxytol IV infusion will be given at a dose of 4mg Fe/kg up to a maximum of 510mg of elemental iron delivered at a rate of 1ml/sec. A second brain MRI will be completed post-infusion

Locations

Country	Name	City	State
United States	Hawaii Center for AIDS	Honolulu	Hawaii

Sponsors (4)

Lead Sponsor	Collaborator
Beau Nakamoto	Hawaii Pacific Health, National Institute of Neurological Disorders and Stroke (NINDS), University of Hawaii

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in the proportion of abnormal MRIs	The proportion of abnormal MRIs will be compared for each group.	Change from Baseline MRI at 4-6 weeks post-infusion MRI
Secondary	Change in quantitative susceptibility mapping (QSM)	Use of QSM to quantitate ferumoxytol accumulation in the brain	Change from Baseline MRI at 4-6 weeks post-infusion MRI