The goal of this study is to evaluate the safety of using the \[5-cyano-N-(4-(4-\[11C\]Methylpiperazin-1-yl)-2-(Piperidin-1-yl)Phenyl)Furan-2-carboxamide\] (\[11C\]CPPC) radiotracer in positron emission tomography (PET) imaging of people with history of COVID-19 infection, with and without symptoms. The investigators are also interested to see whether use of this radiotracer reveals imaging differences between patients with history of COVID-19 infection and still exhibiting symptoms or healthy patients with history of COVID-19 infection but exhibiting no current symptoms.
This is a Phase 1 study of safety and tolerability of an investigational radiotracer drug called \[5-cyano-N-(4-(4-\[11C\]Methylpiperazin-1-yl)-2-(Piperidin-1-yl)Phenyl)Furan-2-carboxamide\] (\[11C\]CPPC). A radiotracer is a substance that chemically marks certain structures in the body. In this case, \[11C\]CPPC highlights structures expressing colony stimulating factor receptor (CSF1R), a receptor that is expressed on microglial cells. A safety and tolerability study is looking to see if there are any unanticipated, possibly harmful, effects of the use of the radiotracer in humans. However, ultimately, the investigators would like to know if this drug can be used to make better images of the brain for patients with history of COVID-19 infection, which could help doctors better understand the disease and help take care of patients suffering from Long COVID symptoms. This study will use a radiotracer to look for a chemical receptor which may be affected in patients who report of Long COVID. After receiving the radiotracer, participants' brains will be scanned with a positron emission tomography (PET) imaging machine. Each participant will also undergo magnetic resonance imaging (MRI) without contrast, detailed cognitive testing and a neurological exam. This study will assess possible associations between COVID-19 infection, cognitive function, other neurological symptoms, and 11C-CPPC PET neuroimaging in subjects.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
DIAGNOSTIC
Masking
NONE
Enrollment
6
A single dose of \[11C\]CPPC (370 megabecquerel (MBq) (X±1 mCi)) intravenously and subsequent positron emission tomography (PET) scan. Other Name: \[5-cyano-N-(4-(4-\[11C\]methylpiperazin-1-yl)-2-(piperidin-1-yl)phenyl)furan-2-carboxamide\]
A single dose of \[11C\]CPPC (370 megabecquerel (MBq) (X±1 mCi)) intravenously and subsequent positron emission tomography (PET) scan. Other Name: \[5-cyano-N-(4-(4-\[11C\]methylpiperazin-1-yl)-2-(piperidin-1-yl)phenyl)furan-2-carboxamide\]
Johns Hopkins Outpatient Center
Baltimore, Maryland, United States
To assess the safety and tolerability of one dose level of [11C]CPPC when administered intravenously.
Safety and tolerability will be determined by evaluation of spontaneously reported adverse events, clinical laboratory test results, physical, cognitive and neurologic exams and imaging (PET).
Time frame: Baseline and up to 2 days follow-up after scan
Safety of use of [11C]CPPC in patients with Long-COVID and healthy participants with history of COVID-19 infection as assessed by a change in complete blood count (CBC) test.
Safety of use of \[11C\]CPPC in positron emission tomography (PET) neuroimaging of patients with Long-Covid and healthy participants with history of COVID-19 infection. Safety will be assessed by monitoring of the complete blood count (CBC) for a change from baseline that is outside of the normal range.
Time frame: Baseline and up to 2 days follow-up after scan
Safety of use of [11C]CPPC in patients with Long-COVID and healthy participants with history of COVID-19 infection as assessed by a change in complete metabolic panel (CMP) test.
Safety of use of \[11C\]CPPC in positron emission tomography (PET) neuroimaging of patients with Long-COVID and healthy participants with history of COVID-19 infection. Safety will be assessed by a change in the CMP from baseline that is outside of the normal range
Time frame: Baseline and up to 2 days follow-up after scan
Biodistribution of [11C]CPPC by PET imaging
Image analysis of PET imaging obtained of patients and healthy participants. The PET compartmental model fits will be applied to the regional time activity curves (TACs) will be first assessed visually before the relative goodness of fit will be assessed using the statistical F test.
Time frame: 1 day
Cognitive function as assessed by the NIH Toolbox Cognition Battery (NIHTB-CB)
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NIH Toolbox Cognition Battery (NIHTB-CB), which is an iPad-based instrument assessing five cognitive sub-domains: Language, Executive Function, Episodic Memory, Processing Speed, and Working Memory. Score range 59 - 140, higher score means better cognition.
Time frame: 1 day
Neuro-psychological assessment as assessed by the The Rey-Osterrieth complex figure test (ROCF)
The Rey-Osterrieth complex figure test (ROCF) is a neuro-psychological assessment in which participants are asked to reproduce a complicated line drawing, first by copying it freehand (recognition), and then drawing from memory (recall). Scoring of drawings is based on the 36-point scoring system (0 being the worst score and 36 the best).
Time frame: 1 day
Global cognitive function as assessed by the Mini-Mental State Exam (MMSE)
The MMSE is a measure of global cognitive function, scores range from 0-30, a lower score indicates greater cognitive impairment.
Time frame: 1 day
Dementia as assessed by the Clinical Dementia Rating (CDR) scale
The Clinical Dementia Rating Dementia Staging Instrument minimum score = 0, maximum score = 18. Low scores indicate less problems.
Time frame: 1 day
Hospital Anxiety and Depression Scale (HADS) score
Scoring for the Hospital Anxiety and Depression scale is 0-21; Normal (0-7); Borderline Abnormal Case (8-10); and Abnormal Case (11-21) higher score indicates worse outcome.
Time frame: 1 day