Heart Failure With Reduced Ejection FractionPhase 1NEURO-HFNCT07856043
[11C]PS13 PET Imaging of Neuroinflammation in Heart Failure With Reduced Ejection Fraction
A Phase 1 study testing [11C]PS13: [carbon-11]PS13; COX-1 PET radioligand and Sacubitril-Valsartan in people with Heart Failure With Reduced Ejection Fraction and Cognitive Impairment, Mild, run by Stony Brook University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 50 to 75 years
- Conditions the study is for
- Heart Failure With Reduced Ejection Fraction, Cognitive Impairment, Mild, Neuroinflammation
- What is being tested?
- [11C]PS13: [carbon-11]PS13; COX-1 PET radioligand and Sacubitril-Valsartan
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Oct 2026to 31 Dec 2028
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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
Show all 19Show fewer
- 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)
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site
Stony Brook University Medical Center
Stony Brook, New York, 11794
Andreas Kalogeropoulos, MD MPH PhD, 404-512-4463, Andreas.Kalogeropoulos@stonybrookmedicine.edu
Min-Jeong Kim, MD PhD, MinJeong.Kim@stonybrookmedicine.edu
About this study
Official title: 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.
Read the 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.
- Conditions
- Heart Failure With Reduced Ejection Fraction, Cognitive Impairment, Mild, Neuroinflammation, Vascular Contributions to Cognitive Impairment and Dementia (VCID)
- Being tested
- [11C]PS13: [carbon-11]PS13; COX-1 PET radioligand, Sacubitril-Valsartan
- Keywords
- [11C]PS13, PET neuroimaging, Cyclooxygenase-1 (COX-1), Microglia, Sacubitril-valsartan, ARNI, Heart failure, Brain inflammation, Cognitive decline
- Medical subject headings
- Cognitive Dysfunction, Neuroinflammatory Diseases, Dementia, Heart Failure, Encephalitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
[11C]PS13: [carbon-11]PS13; COX-1 PET radioligandDrug
[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.
Sacubitril-ValsartanDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: [11C]PS13: [carbon-11]PS13; COX-1 PET radioligand; Drug: Sacubitril-Valsartan |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
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.
Measured: Through study completion, approximately 16 weeks per participant
Change in Regional [11C]PS13 VT in Specific Brain Regions of Interest
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.
Measured: Baseline (Visit 2) and ~12 weeks (Visit 4)
Change in Neurocognitive Performance (Composite Battery)
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.
Measured: Baseline (Visit 1) and ~12 weeks (Visit 4)
Arterial Blood Input Function Quality and Radiometabolite Profile
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.
Measured: Baseline (Visit 2) and ~12 weeks (Visit 4)
Change in Instrumental Activities of Daily Living (IADL / Lawton-Brody Scale)
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.
Measured: Baseline (Visit 2) and ~12 weeks (Visit 4)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Oct 2026
- Study start1 Oct 2026 (estimated)
- Primary completion30 Jun 2028 (estimated)
- Study completion31 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Heart Failure With Reduced Ejection FractionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Single group assignment (within-subject before/after design; no randomization)
- Masking
- None (open label)
- Enrolment
- 18 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Stony Brook University
- Sponsor type
- University, hospital or other
- Collaborators
- American Heart Association, National Institute on Aging (NIA)
- Responsible party
- Principal investigator, Andreas Kalogeropoulos, Stony Brook University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07856043
- Sponsor's protocol ID
- IRB2026-00185
- Other IDs
- R21AG102953, 26RIRA1639136
- Acronym
- NEURO-HF
- Status last verified
- Sep 2026
- First submitted
- 27 Sep 2026
- Last updated
- 2 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Publications
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.
PubMed 39542698Kim 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.
PubMed 32399622Grewal 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.
PubMed 38938237
Study at a glance
From the registry record, last updated by the sponsor on 2 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neuroinflammation as a Therapeutic Target in Heart Failure-Related Cognitive Decline: A Feasibility PET Study
- ClinicalTrials.gov ID
- NCT07856043
- Acronym / sponsor ID
- NEURO-HF / IRB2026-00185
- Conditions
- Heart Failure With Reduced Ejection Fraction, Cognitive Impairment, Mild, Neuroinflammation, Vascular Contributions to Cognitive Impairment and Dementia (VCID)
- Keywords
- [11C]PS13, PET neuroimaging, Cyclooxygenase-1 (COX-1), Microglia, Sacubitril-valsartan, ARNI, Heart failure, Brain inflammation
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 18 participants (estimated)
- Lead sponsor
- Stony Brook UniversityUniversity, hospital or other
- Collaborators
- American Heart Association, National Institute on Aging (NIA)
- Study start
- 1 Oct 2026 (estimated)
- Primary completion
- 30 Jun 2028 (estimated)
- Study completion
- 31 Dec 2028 (estimated)
- First posted
- 2 Oct 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Single group assignment (within-subject before/after design; no randomization)
| Arm | Type | Receives |
|---|---|---|
| HFrEF with Mild Cognitive Impairment - Sacubitril-Valsartan Initiators | Experimental | Drug: [11C]PS13: [carbon-11]PS13; COX-1 PET radioligand, Drug: Sacubitril-ValsartanPatients 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. |
Who may qualify
- Ages
- 50 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (19 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| [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 | HFrEF with Mild Cognitive Impairment - Sacubitril-Valsartan Initiators |
| Sacubitril-ValsartanAngiotensin 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. | Drug | HFrEF with Mild Cognitive Impairment - Sacubitril-Valsartan Initiators |
Primary outcome
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.
5 secondary outcomes
Feasibility: [11C]PS13 PET Scan Completion Rate
Time frame: 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 Neurocognitive Performance (Composite Battery)
Time frame: 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)
Change in Instrumental Activities of Daily Living (IADL / Lawton-Brody Scale)
Time frame: Baseline (Visit 2) and ~12 weeks (Visit 4)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Oct 2026.
- Background: PubMed 39542698Ghazanfari 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.
- Background: PubMed 32399622Kim 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.
- Background: PubMed 38938237Grewal 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.
- Individual participant dataSharing planned: Yes. 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.
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Heart Failure With Reduced Ejection Fraction (HFrEF)
RecruitingObservational study
Descriptive Study of Circulating Gene or Protein Inflammatory Biomarkers and Bioimpedance Parameters in a Population of Patients Hospitalized for Decompensated Heart Failure With Preserved or Mildly Reduced Cardiac Function
Inflammation Biomarkers, Heart Failure
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing [11C]PS13: [carbon-11]PS13; COX-1 PET radioligand and Sacubitril-Valsartan in people with Heart Failure With Reduced Ejection Fraction and Cognitive Impairment, Mild, run by Stony Brook University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 2 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Andreas Kalogeropoulos, MD MPH PhD (404-512-4463, Andreas.Kalogeropoulos@stonybrookmedicine.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07856043, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Oct 2026.