[11C]PS13 PET Imaging of Neuroinflammation in Heart Failure With Reduced Ejection Fraction (NEURO-HF)

September 27, 2026 updated by: Andreas Kalogeropoulos, Stony Brook University

Neuroinflammation as a Therapeutic Target in Heart Failure-Related Cognitive Decline: A Feasibility PET Study

Heart failure reduces the amount of blood the heart pumps, which can lead to memory and thinking problems in many patients. One possible reason is that heart failure triggers brain inflammation, a process in which certain brain immune cells (called microglia) become overactive. A heart failure medication called sacubitril-valsartan has been shown to reduce the risk of developing dementia, but it is not known whether this is because it reduces brain inflammation. This study uses a new experimental brain scan drug called [11C]PS13 (PS13) to measure brain inflammation directly and non-invasively, using a technique called positron emission tomography (PET). PS13 sticks to a molecule called COX-1, which is found mainly in brain immune cells (microglia). By measuring how much PS13 accumulates in the brain, researchers can estimate how much brain inflammation is present. In this pilot study, 18 patients with heart failure and mild memory or thinking problems who are being started on sacubitril-valsartan by their cardiologist (as standard clinical care) will undergo two brain PET scans: one before starting sacubitril-valsartan, and one approximately 12 weeks after. The study will also assess memory, thinking, daily function, mood, and social well-being using standard questionnaires. The study will test whether sacubitril-valsartan is associated with measurable changes in brain inflammation, and whether this type of imaging is feasible in heart failure patients. The study is funded by the American Heart Association and the National Institute on Aging, and an independent Data and Safety Monitoring Board oversees participant safety. The results will be used to design a larger study.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Heart failure with reduced ejection fraction (HFrEF) affects ~6.7 million Americans and is a powerful independent risk factor for accelerated cognitive decline and dementia, playing a major role in vascular contributions to cognitive impairment and dementia (VCID). Neuroinflammation, and particularly microglial activation, is a leading mechanistic hypothesis for HFrEF-associated cognitive decline, driven by chronic cerebral hypoperfusion and systemic inflammatory signaling. However, direct in vivo evidence of neuroinflammation in living HFrEF patients is lacking. Sacubitril-valsartan (an angiotensin receptor-neprilysin inhibitor [ARNI]) is guideline-directed first-line therapy for HFrEF. Beyond established cardiovascular benefits, epidemiological data demonstrate a >30% reduction in incident dementia and cognitive decline with sacubitril-valsartan vs. standard renin-angiotensin inhibitors over 3 years, suggesting neuroprotective properties. These may be mechanistically linked to anti-inflammatory actions via natriuretic peptide signaling and neprilysin-mediated peptide degradation, a hypothesis that has not yet ben=en testedhas not yet been tested in the living human brain. [11C]PS13 is a novel PET radioligand developed at Stony Brook University targeting cyclooxygenase-1 (COX-1), a microglial-specific marker of neuroinflammatory activity.is a novel PET radioligand, co-developed by study co-investigator Dr. Min-Jeong Kim, that selectively targets cyclooxygenase-1 (COX-1), which is primarily localized in microglia and serves as a biomarker of microglial density and neuroinflammatory activity. [11C]PS13 has demonstrated excellent selectivity and signal-to-noise in non-human primates and healthy humans (Kim et al., J Nucl Med 2018; Kim et al., Eur J Nucl Med Mol Imaging 2020), and elevated binding in Alzheimer's disease and dementia with Lewy bodies compared to controls.and increased binding in Alzheimer's disease compared with age-matched healthy controls; work in dementia with Lewy bodies is ongoing. The present study extends [11C]PS13 PET to patients with HFrEF to: (1) establish feasibility of this neuroimaging approach in a cardiac population; (2) characterize baseline brain microglial density (COX-1 expression) in HFrEF patients with mild cognitive impairment; and (3) generate preliminary effect size data for changes in neuroinflammation after sacubitril-valsartan initiation. In addition to PET imaging, participants will undergo a comprehensive neurocognitive assessment at baseline and follow-up, including evaluation of global cognition, processing speed, executive function, free recall, depression, loneliness, social isolation, social network, and instrumental activities of daily living. This AHA-funded pilot will provide the foundational data for a more definitive mechanistic study.The study will enroll 18 participants under a single protocol (6 supported by the American Heart Association and 12 by the National Institute on Aging, R21AG102953), with data pooled for analysis. [11C]PS13 is administered under FDA IND 177118, and an independent, NIA-appointed Data and Safety Monitoring Board oversees participant safety, data quality, and study progress. This pilot will provide the foundational data for a more definitive mechanistic study.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
18

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

50 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Age 50-75 years
  • Diagnosis of HFrEF (left ventricular ejection fraction ≤40% documented by echocardiography or cardiac imaging within the prior 12 months)
  • Montreal Cognitive Assessment (MoCA) score 18-25 (mild cognitive impairment)
  • Being initiated on sacubitril-valsartan per treating cardiologist's clinical judgment in accordance with current guideline-directed medical therapy for HFrEF
  • Clinically stable HF (NYHA functional Class I-III) at time of enrollment
  • Ability to provide written informed consent
  • Ability to lie flat for up to 90 minutes (required for PET scan acquisition)

Exclusion Criteria:

  • Neurologic, psychiatric, or medical condition that may cause cognitive dysfunction or affect study data interpretation (e.g., major stroke, brain tumor, severe TBI, epilepsy, multiple sclerosis, schizophrenia, bipolar disorder)
  • Clinically unstable HF or acute decompensated heart failure within 4 weeks prior to enrollment
  • NYHA functional Class IV heart failure
  • Recent hospitalization for cardiovascular reasons within 4 weeks of enrollment
  • Severe pulmonary congestion or orthopnea precluding lying flat for ~90 minutes
  • Recent cardiac surgery within 3 months of enrollment
  • Implanted cardiac device (e.g., pacemaker, ICD, CRT-D) that is non-MRI-conditional, in the absence of an available clinical brain MRI from within the past 3 years
  • Other implanted device contraindicated for MRI (e.g., deep brain stimulator, cochlear implant, intracranial aneurysm clip)
  • Current drug or alcohol abuse or dependence
  • Recent research radiation exposure that combined with this study would exceed allowable limits as determined by the FDA
  • Inability to remain still on the scanner bed or body weight exceeding scanner maximum
  • Use of NSAIDs other than low-dose aspirin (≤100 mg/day) within 2 weeks prior to each [11C]PS13 PET scan
  • Pregnancy or breastfeeding
  • Severe renal impairment (eGFR <30 mL/min/1.73m²) or other condition that may affect radioligand clearance or biomarker interpretation
  • Active systemic inflammatory or autoimmune disease
  • Peripheral vascular disease or other condition precluding radial arterial catheter placement
  • Anticoagulation at therapeutic levels that would substantially increase the risk of arterial line placement (e.g., warfarin with INR >3.0, therapeutic heparin); patients on direct oral anticoagulants (DOACs) are assessed individually by the study physician
  • Whole blood or plasma donation within 8 weeks (56 days) before the first PET scan, or unwillingness to refrain from blood donation for the duration of study participation
  • Non-English speaking (the MoCA and the consent process require English-language comprehension)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: HFrEF with Mild Cognitive Impairment - Sacubitril-Valsartan Initiators

Patients with HFrEF (LVEF ≤40%) and mild cognitive impairment (MoCA 18-25) who are being initiated on sacubitril-valsartan per their cardiologist's clinical judgment. Participants undergo [11C]PS13 PET brain imaging with arterial blood sampling and brain MRI at baseline (prior to sacubitril-valsartan initiation) and at approximately 12 weeks after initiation.
Drug: [11C]PS13: [carbon-11]PS13; COX-1 PET radioligand

[11C]PS13 is an investigational positron emission tomography (PET) radioligand targeting cyclooxygenase-1 (COX-1), an enzyme primarily localized in microglia involved in neuroinflammation. Synthesized on the day of each scan at the Stony Brook BAHL cGMP or FERM facility, administered as a single intravenous bolus (up to 20 mCi) per PET visit. Administered under FDA IND 177118 (21 CFR Part 312). Not FDA-approved; experimental.

Drug: Sacubitril-Valsartan

Angiotensin receptor-neprilysin inhibitor (ARNI) initiated by the participant's treating cardiologist per ACC/AHA/HFSA guideline-directed medical therapy for HFrEF. The dose, titration, and monitoring of sacubitril-valsartan are entirely at the discretion of the treating cardiologist and are not research procedures. The timing of the follow-up PET scan (~12 weeks post-initiation) is aligned with expected clinical stabilization on the drug.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change in [11C]PS13 Total Distribution Volume (VT) in Global Gray Matter
Time Frame: Baseline (Visit 2, prior to sacubitril-valsartan initiation) and approximately 12 weeks after initiation (Visit 4)

Change in regional [11C]PS13 total distribution volume (VT, mL/cm³), a quantitative index of COX-1 binding (microglial density), in global cortical gray matter. VT will be calculated using two-tissue compartmental modeling with an arterial blood input function (arterial plasma concentration corrected for radiometabolites). A reduction in VT at follow-up relative to baseline is hypothesized to reflect sacubitril-valsartan-mediated attenuation of microglial neuroinflammation.
Baseline (Visit 2, prior to sacubitril-valsartan initiation) and approximately 12 weeks after initiation (Visit 4)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Feasibility: [11C]PS13 PET Scan Completion Rate
Time Frame: Through study completion, approximately 16 weeks per participant

Proportion of enrolled participants who successfully complete both PET scan visits with adequate image quality for quantitative analysis. Arterial line success rate and reasons for scan non-completion will be documented. A completion rate of ≥80% will be considered evidence of feasibility in this cardiac population.
Through study completion, approximately 16 weeks per participant
Change in Regional [11C]PS13 VT in Specific Brain Regions of Interest
Time Frame: Baseline (Visit 2) and ~12 weeks (Visit 4)

Change in [11C]PS13 VT in pre-specified regions of interest including frontal cortex, temporal cortex, hippocampus, parietal cortex, occipital cortex, cingulate cortex, and thalamus, evaluated using PET-MRI co-registration and Logan graphical analysis. Regional analysis will explore the spatial pattern of neuroinflammation in HFrEF and its response to sacubitril-valsartan.
Baseline (Visit 2) and ~12 weeks (Visit 4)
Change in Neurocognitive Performance (Composite Battery)
Time Frame: Baseline (Visit 1) and ~12 weeks (Visit 4)

Change in performance on the standardized neurocognitive battery instruments administered at both baseline (Visit 1) and follow-up (Visit 4): Montreal Cognitive Assessment (MoCA; global cognition), Digit Symbol Substitution Test (DSST; processing speed), Trail Making Test Parts A and B (TMT-A/B; processing speed and executive function), Free and Cued Selective Reminding Test immediate and delayed recall (FCSRT; episodic memory), and Geriatric Depression Scale-15 item version (GDS-15; depression symptoms). The battery takes approximately 45-60 minutes to administer. Spearman correlations between ΔVTPET and changes in individual test scores will be explored as exploratory analyses.
Baseline (Visit 1) and ~12 weeks (Visit 4)
Arterial Blood Input Function Quality and Radiometabolite Profile
Time Frame: Baseline (Visit 2) and ~12 weeks (Visit 4)

Characterization of the [11C]PS13 arterial plasma input function and radiometabolite-corrected curves in HFrEF patients at both time points. This will inform whether the pharmacokinetic profile of [11C]PS13 in HFrEF patients is comparable to prior neurological cohorts, a key methodological feasibility outcome.
Baseline (Visit 2) and ~12 weeks (Visit 4)
Change in Instrumental Activities of Daily Living (IADL / Lawton-Brody Scale)
Time Frame: Baseline (Visit 2) and ~12 weeks (Visit 4)

Characterization of the [11C]PS13 arterial plasma input function and radiometabolite-corrected curves in HFrEF patients at both time points. This will inform whether the pharmacokinetic profile of [11C]PS13 in HFrEF patients is comparable to prior neurological cohorts, a key methodological feasibility outcome.
Baseline (Visit 2) and ~12 weeks (Visit 4)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Stony Brook University

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Institute on Aging (NIA)
American Heart Association

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 1, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 30, 2028

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 31, 2028

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 27, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 27, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 2, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 2, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 27, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • IRB2026-00185
  • R21AG102953 (U.S. NIH Grant/Contract)
  • 26RIRA1639136 (Other Grant/Funding Number: American Heart Association)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

De-identified participant-level brain PET imaging data ([11C]PS13), structural MRI data (MP-RAGE, T2-FLAIR), cognitive assessment scores (MoCA, DSST, TMT-A/B, FCSRT), and associated clinical metadata (demographics, HF characteristics, NT-proBNP) will be shared. Data will be formatted in Brain Imaging Data Structure (BIDS) standard per Knudsen et al. (J Cereb Blood Flow Metab 2020). Plasma biospecimens will be transferred to NCRAD after 5 years. Analytic code and the statistical analysis plan will also be shared.

IPD Sharing Time Frame

De-identified imaging data, cognitive scores, and clinical metadata will be made available no later than the time of the primary associated publication, or at the end of the study performance period, whichever comes first. Supporting documents (SAP, ICF, analytic code) will be shared simultaneously. All shared data will remain available indefinitely with no end date.

IPD Sharing Access Criteria

Qualified researchers may request access to de-identified brain PET and MRI images, cognitive assessment scores, and clinical metadata via OpenNeuro PET Archive (openneuro.org). Access is initially granted through the repository review process. After an optional 36-month grace period from initial deposit, data will be released under a Creative Commons CC0 license for unrestricted reuse. Facial features will be removed from structural MRI prior to upload.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • ANALYTIC_CODE
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

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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