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

NCT05350774 | Enrolling By Invitation Phase 2 FDA Drug

• 2 other identifiers: 10000711000711-N
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

Background: COVID-19 can cause problems in different parts of the body. For most people, it causes fevers or trouble breathing. Some people might not recover all the way. Researchers want to see if a treatment can help with people who have recovered from COVID-19 but still have symptoms ("Long COVID"). Objective: To learn if human immunoglobulin (IVIG) will help with neurological symptoms of Long COVID. Eligibility: Adults ages 18 and older who had COVID-19 at least 12 weeks ago and have ongoing neurologic symptoms, such as dizziness, trouble walking, or problems with strength. Design: Participants will be screened with a medical record review. Participants will have a medical history and a physical exam and complete questionnaires about their health and quality of life. They will have a spinal tap. They will give blood samples. They will discuss their symptoms with a neurologist and have a neurological exam. Participants will take memory and thinking tests using a tablet. The tests will take 1 hour to complete. They will also take a smell and taste test. It will take approximately 30 minutes to complete. Participants will lie on a table that tilts for up to 40 minutes. Their blood pressure and heart rate will be monitored. Blood will be taken through an intravenous (IV) catheter. Participants will receive either IVIG, or saline by IV for 5 days. Then the participants will receive IVIG if they first received saline or saline if they first received IVIG by IV for another 5 days. They will not know what they receive. Participants will have an MRI of the brain if they have not had one recently. They will receive a contrast agent by IV as part of the MRI scan. Participants will be on the study for up to 4 months. They will have follow-up visits at the clinical center as well as fill out questionnaires at home. They may be asked to continue follow-up.

Conditions

Neuroinflammation; Microvascular Thrombosis; Systemic Inflammation

Keywords

Long Haul Covid; COVID-19; Long Covid

Outcome Measures

Primary Outcomes (1)

• Effects of intravenous immunoglobulin therapy

  Comparison of proportion of participants with a clinically meaningful change in Health Utilities Index Mark 3 (HUI3) after receiving either IVIg or placebo at Week 2.

  2 weeks

Secondary Outcomes (1)

• Investigate laboratory effects

  2 weeks

Study Arms (2)

IVIg arm

EXPERIMENTAL

IVIg arm IV immunoglobulin 0.4g/kg/day for 5 days

Drug: IV immunoglobulin

Placebo arm

PLACEBO COMPARATOR

equivalent volume of Normal Saline for 5 days

Drug: IV normal saline

Interventions

IV immunoglobulin DRUG

IVIg - IV immunoglobulin 0.4g/kg/day for 5 days

IVIg arm

IV normal saline DRUG

IV normal saline 250ml for 5 days

Placebo arm

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• National Institute of Neurological Disorders and Stroke (NINDS): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Neuroinflammatory Diseases; Post-Acute COVID-19 Syndrome; COVID-19

Interventions

Saline Solution; Immunoglobulins, Intravenous

Condition Hierarchy (Ancestors)

Nervous System Diseases; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Post-Infectious Disorders; Chronic Disease; Disease Attributes

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations; Immunoglobulin G; Immunoglobulin Isotypes; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Avindra Nath, M.D.

  National Institute of Neurological Disorders and Stroke (NINDS)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 20, 2022
• First Posted: April 28, 2022
• Study Start: July 10, 2023
• Primary Completion (Estimated): December 15, 2026
• Study Completion (Estimated): December 15, 2026
• Last Updated: June 12, 2026

Record last verified: 2026-06-10

Locations

US (1)