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

Phase 2
Conditions
Systemic Inflammation
Microvascular Thrombosis
Neuroinflammation
Interventions
Drug: IV immunoglobulin
Drug: IV normal saline
Registration Number
NCT05350774
Lead Sponsor
National Institute of Neurological Disorders and Stroke (NINDS)
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....

Detailed Description

Study Description:

This study will evaluate the clinical and laboratory effects of immunoglobulin therapy in patients who recovered from acute mild-moderate COVID-19 infection but still have persistent neurologic symptoms. Despite clinical recovery from the acute infection, some individuals continue to experience ongoing symptoms, at times several months after recovery, and many of these symptoms are neurologic. Some features suggest that this is a post-infectious immune-mediated process, and anecdotally patients have responded well to immunoglobulin therapy. This study will evaluate the clinical and laboratory effects of intravenous immunoglobulin therapy compared to placebo using a cross-over trial design. It is hypothesized that immunoglobulin therapy could have positive clinical and laboratory effects on patients with persistent neurological symptoms.

Objectives:

Primary Objective: To compare the clinical efficacy of intravenous immunoglobulin therapy to placebo in ameliorating the neurological post-acute sequalae of SARS-CoV-2 infection.

Secondary objective: To determine the clinical effects of intravenous immunoglobulin therapy in patients with neurological post-acute sequalae of SARS-CoV-2 infection.

Exploratory objective: To investigate the laboratory effects of intravenous immunoglobulin therapy in patients with neurological post-acute sequalae of SARS-CoV-2 infection.

Endpoints:

Primary endpoint:

Proportion of participants with a clinically meaningful change in Health Utilities Index Mark 3 (HUI3) 2 weeks after intravenous immunoglobulin therapy compared with 2 weeks after placebo.

Secondary endpoints:

* Change in functional / patient-reported scales:

* WHO post COVID-19 functional scale

* Post-COVID-19 Functional Status (PCFS) scale (0-4).

* COVID-19 Yorkshire Rehabilitation Scale

* PROMIS Global Health score

* PROMIS Depression score

* PROMIS anxiety score

* Change in clinical scales:

* Montreal Cognitive Assessment (MoCA)

* Brief tablet-based Neuropsychiatric evaluation

* Karnofsky Performance Status (KPS)

Exploratory endpoints:

* Autonomic testing - Change in the number and character of test results indicating autonomic nervous system dysfunctions as evidenced by abnormal physiological responses to the Valsalva maneuver or head-up tilting.

* Change in immunological markers:

* Cytokine levels

* Cell markers per flow cytometry

* SCENTinel, Olfactory testing, Monell

Recruitment & Eligibility

Status
ENROLLING_BY_INVITATION
Sex
All
Target Recruitment
45
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
IVIg armIV immunoglobulinIVIg arm IV immunoglobulin 0.4g/kg/day for 5 days
Placebo armIV normal salineequivalent volume of Normal Saline for 5 days
Primary Outcome Measures
NameTimeMethod
Effects of intravenous immunoglobulin therapy2 weeks

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.

Secondary Outcome Measures
NameTimeMethod
Investigate laboratory effects2 weeks

Comparison of change in functional / patient-reported scales at 2 weeks after receiving each study intervention:a.\<TAB\>WHO post-COVID functional scale b.\<TAB\>PCFSc.\<TAB\>COVID-19 Yorkshire Rehabilitation Scaled.\<TAB\>PROMIS GHe.\<TAB\>PROMIS Depression f.\<TAB\>PROMIS Anxiety Comparison of change in clinical scales 2 weeks after receiving each study intervention:g.\<TAB\>Montreal Cognitive Assessment (MoCA)h.\<TAB\>Brief tablet-based Neuropsychiatric evaluation i.\<TAB\>Karnofsky Performance Status (KPS)

Trial Locations

Locations (1)

National Institutes of Health Clinical Center

🇺🇸

Bethesda, Maryland, United States

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