[11C]PS13 PET Imaging of Neuroinflammation in Heart Failure With Reduced Ejection Fraction

NCT07856043 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: IRB2026-00185R21AG10295326RIRA1639136
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Cognitive Impairment, Mild; Neuroinflammation; Vascular Contributions to Cognitive Impairment and Dementia (VCID); Heart Failure With Reduced Ejection Fraction

Keywords

[11C]PS13; PET neuroimaging; Cyclooxygenase-1 (COX-1); Microglia; Sacubitril-valsartan; ARNI; Heart failure; Brain inflammation; Cognitive decline

Outcome Measures

Primary Outcomes (1)

• Change in [11C]PS13 Total Distribution Volume (VT) in Global Gray Matter

  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 Outcomes (5)

• Feasibility: [11C]PS13 PET Scan Completion Rate

  Through study completion, approximately 16 weeks per participant

• Change in Regional [11C]PS13 VT in Specific Brain Regions of Interest

  Baseline (Visit 2) and ~12 weeks (Visit 4)

• Change in Neurocognitive Performance (Composite Battery)

  Baseline (Visit 1) and ~12 weeks (Visit 4)

• Arterial Blood Input Function Quality and Radiometabolite Profile

  Baseline (Visit 2) and ~12 weeks (Visit 4)

• Change in Instrumental Activities of Daily Living (IADL / Lawton-Brody Scale)

  Baseline (Visit 2) and ~12 weeks (Visit 4)

Study Arms (1)

HFrEF with Mild Cognitive Impairment - Sacubitril-Valsartan Initiators

EXPERIMENTAL

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; Drug: Sacubitril-Valsartan

Interventions

[11C]PS13: [carbon-11]PS13; COX-1 PET radioligand DRUG

\[11C\]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.

HFrEF with Mild Cognitive Impairment - Sacubitril-Valsartan Initiators

Sacubitril-Valsartan DRUG

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.

HFrEF with Mild Cognitive Impairment - Sacubitril-Valsartan Initiators

Eligibility Criteria

• Age: 50 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Stony Brook University: lead
• National Institute on Aging (NIA): collaborator
• American Heart Association: collaborator

Study Sites (1)

Stony Brook University Medical Center

Stony Brook, New York, 11794, United States

Location

Related Publications (3)

• Ghazanfari N, Liow JS, Kim MJ, Cureton R, Lee A, Knoer C, Jenkins M, Hong J, Santamaria JAM, Shetty HU, Galassi A, Wighton P, Norgaard M, Greve DN, Zoghbi SS, Pike VW, Innis RB, Zanotti-Fregonara P. [11C]PS13 Demonstrates Pharmacologically Selective and Substantial Binding to Cyclooxygenase-1 in the Human Brain. J Nucl Med. 2025 Jan 3;66(1):117-122. doi: 10.2967/jnumed.124.267928.

  PMID: 39542698 BACKGROUND

• Kim MJ, Lee JH, Juarez Anaya F, Hong J, Miller W, Telu S, Singh P, Cortes MY, Henry K, Tye GL, Frankland MP, Montero Santamaria JA, Liow JS, Zoghbi SS, Fujita M, Pike VW, Innis RB. First-in-human evaluation of [11C]PS13, a novel PET radioligand, to quantify cyclooxygenase-1 in the brain. Eur J Nucl Med Mol Imaging. 2020 Dec;47(13):3143-3151. doi: 10.1007/s00259-020-04855-2. Epub 2020 May 12.

  PMID: 32399622 BACKGROUND

• Grewal PK, Abboud A, Myserlis EP, Goldschmidt ME, Butler J, Skopicki HA, Kalogeropoulos AP. Sacubitril/Valsartan and Cognitive Outcomes in Heart Failure With Reduced Ejection Fraction. JACC Adv. 2023 Jun 7;2(4):100372. doi: 10.1016/j.jacadv.2023.100372. eCollection 2023 Jun.

  PMID: 38938237 BACKGROUND

MeSH Terms

Conditions

Cognitive Dysfunction; Neuroinflammatory Diseases; Dementia; Heart Failure; Encephalitis

Interventions

11C-PS13; sacubitril and valsartan sodium hydrate drug combination

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Nervous System Diseases; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Brain Diseases; Central Nervous System Diseases; Heart Diseases; Cardiovascular Diseases

Central Study Contacts

Andreas Kalogeropoulos, MD MPH PhD

CONTACT

404-512-4463; Andreas.Kalogeropoulos@stonybrookmedicine.edu

Min-Jeong Kim, MD PhD

CONTACT

631-638-3154; MinJeong.Kim@stonybrookmedicine.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Cardiovascualr Research

Model Details: Single group assignment (within-subject before/after design; no randomization)

Study Record Dates

• First Submitted: September 27, 2026
• First Posted: October 2, 2026
• Study Start: October 1, 2026
• Primary Completion (Estimated): June 30, 2028
• Study Completion (Estimated): December 31, 2028
• Last Updated: October 2, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• 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.
• 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.

Locations

US (1)