Clinical trial NCT06223971: Long COVID-19 [11C]CPPC Study
Official title: A Phase l Study to Assess the Safety and Tolerability of PET Imaging With [11 C]CPPC [5-cyano-N-( 4-( 4-[l l CJ me1hylpiperazin-l-yl)-2-(Piperidin-l-yl)Phenyl)Furan-2-carboxamide] Radioligand and Magnetic Resonance (MR) Imaging in Patients With Long COVID.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: EARLY_PHASE1
Conditions: COVID Long-Haul
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
Collaborators: name: Radiological Society of North America
First posted: 2024-01-25
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

1. Have the ability to understand the requirements of the study, provide written informed consent, understand and provide written authorization for the use and disclosure of Protected Health Information (PHI) \[per Health Insurance Portability and Accountability Act (HIPAA) Privacy Ruling\] and comply with the study procedures.
2. Documented history of COVID infection at least 6 - 12 months before enrollment.
3. Men and women at least 18 years old.
4. Women must have a negative serum pregnancy test and practice an acceptable method of contraception or be of non-childbearing potential (post-menopausal for at least 2 years or who have undergone hysterectomy, oophorectomy or surgical sterilization).
5. Geographic accessibility to the study center and the ability to travel to the clinic for study visits.
6. Agrees to the visit schedule as outlined in the informed consent.
7. Pre-study labs within normal range, or if abnormal, deemed not clinically significant by the site investigator.

Exclusion Criteria:

1. History of recent nosocomial infection.
2. History of chronic neurological disorder, such as epilepsy, or structural Central Nervous System (CNS) abnormality such as stroke or arteriovenous malformation.
3. History of head trauma with prolonged loss of consciousness (\>10 minutes) or any neurological condition including stroke, seizure (excluding childhood febrile seizure), or visible structural abnormality on prior MRI.
4. Active or recent (in the past year) substance dependence (drugs-including nicotine, marijuana or alcohol).
5. Receipt of any investigational drug, device or biologic within 30 days of administration of study compound.
6. Use of anti-inflammatory medications, immunosuppressants, or benzodiazepines within 7 days of administration of study compound.
7. Any concomitant medical disease or condition limiting the safety to participate including, but not limited to:

   * Coagulopathy
   * Active infection
8. Contraindications to MRI scanning to include pacemakers, metallic implants/prosthesis or prohibitive claustrophobia, etc.
9. Contraindications to PET scanning to include pregnancy, etc.
10. Any medical condition that in the opinion of the study investigators would constitute a safety risk to the subject.
11. Any radiation exposure in the past calendar year that in combination with the radiation exposure from this study would exceed 5 rem.
12. Any history of learning disability or special education (due to the potential to affect performance on neuropsychological testing).

Primary outcomes:
measure: To assess the safety and tolerability of one dose level of [11C]CPPC when administered intravenously.
timeFrame: Baseline and up to 2 days follow-up after scan
measure: 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.
timeFrame: Baseline and up to 2 days follow-up after scan
measure: 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.
timeFrame: Baseline and up to 2 days follow-up after scan
Secondary outcomes:
measure: Biodistribution of [11C]CPPC by PET imaging
timeFrame: 1 day
measure: Cognitive function as assessed by the NIH Toolbox Cognition Battery (NIHTB-CB)
timeFrame: 1 day
measure: Neuro-psychological assessment as assessed by the The Rey-Osterrieth complex figure test (ROCF)
timeFrame: 1 day
measure: Global cognitive function as assessed by the Mini-Mental State Exam (MMSE)
timeFrame: 1 day
measure: Dementia as assessed by the Clinical Dementia Rating (CDR) scale
timeFrame: 1 day
measure: Hospital Anxiety and Depression Scale (HADS) score
timeFrame: 1 day
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Johns Hopkins Outpatient Center
state: Maryland
Study officials:
affiliation: Johns Hopkins University
name: Licia Luna, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: