Immunotherapy for Neurological Post-Acute Sequelae of SARS-CoV-2

Launched by NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE (NINDS) · Apr 27, 2022

Keywords

ClinConnect Summary

This NIH study tests whether intravenous immunoglobulin (IVIg) helps people who have recovered from COVID-19 but still have ongoing neurological symptoms (often called Long COVID). In this Phase 2 trial, participants are randomly assigned to receive IVIg or a saline placebo for 5 days, and then they switch to the other treatment for another 5 days. Everyone and the study team are kept unaware of which treatment is given first, so the results are less biased. The main question is whether IVIg leads to a meaningful improvement in daily life and health-related quality of life about 2 weeks after treatment.

Eligible participants are adults 18 and older who had mild-to-moderate COVID-19 at least 12 weeks ago and still have persistent neurological symptoms (like dizziness, trouble walking, weakness, or thinking problems) with a certain level of symptom burden. The study involves a screening visit, medical history and exams, questionnaires, a spinal tap, blood tests, a neurologic exam, and cognitive and functional tests (some done on a tablet). Participants may also have an MRI brain scan if they haven’t had one recently. The trial includes IV infusions for 5 days, with follow-up visits for up to about 4 months. It is conducted at the NIH Clinical Center in Bethesda, MD, led by Avindra Nath, M.D. Completion is expected in December 2025.

Gender

ALL

Eligibility criteria

• * INCLUSION CRITERIA:
• In order to be eligible to participate in this study, an individual must meet all of the following criteria:
• • Stated willingness to comply with all study procedures and availability for the duration of the study.
• • Male or female, aged at least 18 and older.
• • Meets the inclusion/exclusion criteria and is enrolled in Phase A of Protocol 000089 "Post-Coronavirus Disease 19 Convalescence at the National Institutes of Health."
• • Previously diagnosed with mild-moderate COVID-19 (WHO Clinical Progression Scale between 2-5. Patients with severe acute COVID-19 requiring hospitalization or ICU care are excluded. Enrollment could take place 12 weeks after the diagnosis of acute COVID-19.
• • Prior COVID-19 diagnosis confirmed by patient reported infection followed by confirmatory nucleocapsid antibody testing or a positive SARS-CoV-2 PCR test result from the time of infection.
• • Exhibiting persistent neurologic symptoms evidenced by a self-reported illness narrative of the development of persistent PASC symptoms after recovering from a SARS-CoV-2 infection. These include symptoms such as fatigue, cognitive difficulties, orthostatic intolerance, and any ongoing issues with gait instability, vision, speech, swallowing, sensation or strength.
• • Non-negligible PASC symptom severity, as determined using PCFS (minimal score of 2).
• • Ability of subject to understand and the willingness to sign a written informed consent document.
• • Prior completion of a clinical brain MRI after the diagnosis of COVID-19, or willingness to complete a brain MRI.
• • Meets current Clinical Center HES' policy for discontinuing isolation and quarantine for COVID-19.
• EXCLUSION CRITERIA:
• An individual who meets any of the following criteria will be excluded from participation in this study:
• • - For participants who have not completed a brain MRI since onset of symptoms: inability to complete brain MRI with gadolinium including contraindicated metal in the body, prior allergic reaction to gadolinium, eGFR \<45 mmol/L, pregnancy or lactation, or claustrophobia that is unable to be adequately treated with a low dose oral
• • benzodiazepine.
• • Contraindication to a research lumbar puncture, including use of anticoagulant medication, platelets \< 50,000/uL, PT or PTT \>1.5 x ULN for the NIH Clinical Center, or otherwise inability to complete the procedure.
• • A condition that would significantly confound interpretation of the clinical and research tests as determined by the study investigators. This could include: traumatic brain injury, substance use disorder, active malignancy, systemic immunologic disorders, current or previous long-term immune suppressive therapy.
• • Received a SARS-CoV-2 vaccine dose within less than 4 weeks of enrollment or is planning for any additional vaccines during the course of the study.
• • Prior experimental treatment for PASC with immunoglobulins.
• • Current medications include oral steroids or other immunosuppressive medications.
• • Active participation in a clinical protocol which includes any intervention that may affect the results of the current study.
• * Contraindication of intravenous immunoglobulins, including:
• • Renal insufficiency (eGFR\<45mmol/L)
• • IgA deficiency
• • History of ischemic heart disease
• • Peripheral vascular disease
• • Cerebrovascular disease
• • Previously diagnosed hypercoagulability syndrome including antiphospholipid antibody syndrome, Protein C/S deficiency, Factor V Leiden, Antithrombin deficiency, MTHFR homozygosity
• • Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than 3.0 times the upper limit of normal.precluding the use of acetaminophen.
• • Previously documented anaphylaxis or severe systemic reaction to immunoglobulins, acetaminophen, or diphenhydramine.
• • A severe psychiatric condition, which based on the assessment of the study investigators, will impact the ability to complete the 12-week study course.