Imaging brain inflammation in people with long COVID symptoms

PET Imaging of Cyclooxygenase-1 in Participants With Neurological Manifestations of Post-Acute Sequelae of SARS-CoV-2 Infection (PASC)

This study is testing if a brain scan can show signs of inflammation in people aged 18 to 70 who have neurological symptoms after COVID-19, and whether a treatment called IVIg can help them feel better.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 60 (estimated)
• Ages: 18 Years to 70 Years
• Sex: All
• Sponsor: National Institutes of Health Clinical Center (CC) (NIH)
• Drugs / interventions: Immunotherapy, radiation, methotrexate
• Locations: 1 site (Bethesda, Maryland)
• Trial ID: NCT06920628 on ClinicalTrials.gov

What this trial studies

This study aims to investigate the presence of cyclooxygenase-1 (COX-1), a biomarker for neuroinflammation, in the brains of individuals experiencing neurological symptoms following COVID-19. Participants aged 18 to 70 with post-COVID brain disorders will undergo imaging scans using a radioactive tracer to assess COX-1 levels compared to healthy volunteers. The study will also evaluate the effects of intravenous immunoglobulin (IVIg) treatment on these participants. Up to five clinic visits will be required for screening, blood tests, and imaging assessments.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 to 70 with neurological manifestations of post-acute sequelae of SARS-CoV-2 infection.

Not a fit: Patients who do not have neurological symptoms following COVID-19 or are outside the age range may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to better understanding and treatment options for individuals suffering from long-term neurological effects of COVID-19.

How similar studies have performed: Other studies have explored neuroinflammation in post-COVID conditions, but this specific approach using COX-1 imaging is novel.

Eligibility criteria

* INCLUSION CRITERIA:

Patients: To be eligible for this study, Neuro-PASC participants must meet all of the following criteria:

* Aged 18 to 70 years of age.
* Participants must be in good general health as evidenced by medical history and physical examination.
* Each participant must have a level of understanding sufficient to agree to all required tests and examinations and sign an informed consent document.
* Participants must have undergone a screening assessment under protocol #000089, Natural History of Post-Coronavirus Disease 19 Convalescence at the National Institutes of Health or #000711 Immunotherapy for Neurological Post-Acute Sequelae of SARSCoV-2 (INPASC) and determined to have neuro-PASC.
* Participants must have had their radial artery pulse checked for the presence of adequate ulnar collateral flow and the absence of any metal or foreign objects in both wrists.
* Participants must agree to adhere to the lifestyle considerations.

Healthy Volunteers: To be eligible to participate in this study, healthy volunteers must meet all of the following criteria:

* Aged 18 to 70 years of age.
* Able to provide informed consent.
* Be in good general health, as evidenced by medical history and physical examination, and have no cognitive impairment.
* Does not have an active SARS-CoV-2 infection. The protocol will conform with NIH CC standards for documenting a participant does not have active SARS-CoV-2 infection. This may include screening interviews and/or testing.
* Participants must be at least six weeks out since the onset of SARS-CoV-2 symptoms with no fever for at least one week.
* Participants must report having at least one prior SARS-CoV-2 infection.
* Be enrolled in 01M0254, The Evaluation of Participants with Mood and Anxiety Disorders and Healthy Volunteers or 17M0181, Recruitment and Characterization of Healthy Research Volunteers for NIMH Intramural Studies .
* Have had their radial artery pulse checked for the presence of adequate ulnar collateral flow and the absence of any metal or foreign objects in both wrists.
* Agree to adhere to the lifestyle considerations.

EXCLUSION CRITERIA:

Participants with Neuro-PASC who meet any of the following criteria will be excluded from participation in this study:

* Clinically significant abnormalities on EKG or laboratory testing based on individual clinical judgement. This includes CBC and acute care panel (Na, K, Cl, CO2, creatinine, glucose, urea nitrogen). Any lab value that is two times the upper limit or lower values, as per the investigator s judgment. Creatinine level \>1.3 mg/dL.
* Participants should not have taken Non-Steroidal Anti-Inflammatory Drug (NSAID)s for two weeks prior to each PET scan. Corticosteroids (with the exception of topical steroids), or immunosuppressants (e.g. methotrexate) must not have been taken within one month prior to each PET scan.
* Participants must not have substance use disorder or alcohol use disorder. However, alcohol or cannabis use by themselves are not exclusion criteria, unless that use impairs daily life functions.
* Participants who have an unstable medical condition that, in the opinion of the investigators, makes participation unsafe (e.g., an active infection or untreated malignancy).
* Are unable to travel to the NIH.
* Have recent exposure to radiation related to research (e.g., PET from other research) that, when combined with this study, would be above the allowable limits as determined by the study team.
* Have an inability to lie flat and/or lie still on the camera bed for at least two hours,including claustrophobia, overweight greater than the maximum for the scanner, and uncontrollable behavioral symptoms, which will be screened by an interview with the participant during the screening visit.
* Are unable to have an MRI scan (e.g., because of pacemakers or other implanted electrical devices, brain stimulators, dental implants, aneurysm clips (metal clips on the wall of a large artery), metallic prostheses (including metal pins and rods, heart valves, and cochlear implants), permanent eyeliner, implanted delivery pumps, shrapnel fragments, or metal fragments in the eye.
* Pregnancy or Breastfeeding Women.
* HIV Infection.

Healthy volunteers who meet any of the following criteria will be excluded from participation in this study:

* Clinically significant abnormalities on EKG or laboratory testing. This includes CBC and acute care panel (Na, K, Cl, CO2, creatinine, glucose, urea nitrogen).
* Participants should not have taken Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) for two weeks prior to the PET scan. Corticosteroids (with the exception of topical steroids), or immunosuppressants (e.g., methotrexate) must not have been taken within one month prior to the PET scan.
* Participants with an active SARS-CoV-2 infection.
* Participants must not have substance use disorder or alcohol use disorder. However, alcohol or cannabis use by themselves are not exclusion criteria, unless that use impairs daily life functions.
* Are unable to travel to the NIH.
* Have recent exposure to radiation related to research (e.g., PET from other research) that, when combined with this study, would be above the allowable limits.
* Have an inability to lie flat and/or lie still on the camera bed for at least two hours, including claustrophobia, overweight greater than the maximum for the scanner, and uncontrollable behavioral symptoms, which will be screened by an interview with the participant during the screening visit.
* Are unable to have an MRI scan (e.g., because of pacemakers or other implanted electrical devices, brain stimulators, dental implants, aneurysm clips (metal clips on the wall of a large artery), metallic prostheses (including metal pins and rods, heart valves, and cochlear implants), permanent eyeliner, implanted delivery pumps, shrapnel fragments, or metal fragments in the eye.
* Pregnancy or Breastfeeding Women.
* HIV Infection.

Where this trial is running

Bethesda, Maryland

• National Institutes of Health Clinical Center — Bethesda, Maryland, United States (Recruiting)

Study contacts

• Principal investigator: Robert B Innis, M.D. — National Institute of Mental Health (NIMH)
• Study coordinator: Tara N Turon, C.R.N.P.

Conditions Long COVID; Post Acute Sequelae of COVID-19; Inflammation; COVID; SARS; Neuro-PASC