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An Observational Study of Neurologic Function After COVID-19 Infection

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04564287
Recruitment Status : Recruiting
First Posted : September 25, 2020
Last Update Posted : June 24, 2022
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Neurological Disorders and Stroke (NINDS) )

Brief Summary:

Background:

COVID-19 is an infection caused by a coronavirus. It can affect different parts of the body. For most people, it causes fevers or trouble breathing. Some people can have symptoms long after they recover. Researchers want to learn if there are signs of changes in the nervous system that may be related to COVID-19.

Objective:

To test the nervous system (the brain and nerves) in people who have had COVID-19 yet still have certain symptoms even after recovering.

Eligibility:

People age 18 and older who had COVID-19 and still have neurologic symptoms after they recovered from the initial infection.

Design:

Participants will be screened with a medical record review.

Participants will have a neurological exam. They will complete pen-and-paper tests of their memory and thinking. They will complete a smell test with 'scratch-and-sniff' booklets.

They will give blood samples.

Participants will have magnetic resonance imaging (MRI) of the brain. Soft padding or a coil will be placed around their head. They will lie on a table that slides in and out of the MRI scanner. They will get a contrast dye through an intravenous (IV) catheter.

Participants blood pressure, blood flow, skin temperature, sweating, and breathing will be monitored.

Participants will have an electrocardiogram to measure heart function.

Participants will blow into a mouthpiece for several seconds.

Participants will lie on a table that has a motor. The motor tilts the table. Participants will have blood drawn through an IV as the table tilts.

Participants will have a lumbar puncture. A small needle will be inserted into the spinal canal to obtain fluid.

Participants may repeat some tests 8 weeks to 1 year later.


Condition or disease
COVID-19

Detailed Description:

Study Description: This study will characterize ongoing neurologic abnormalities in those who recovered from acute COVID-19 infection yet have persistent neurologic symptoms. Despite clinical recovery from the acute infection, some individuals continue to experience ongoing symptoms, at times several months after recovery (Post-Acute Sequelae of SARS CoV-2 Infection, PASC), and many of these symptoms are neurologic (neuro-PASC). The NIH Clinical Center provides the breadth of expertise and resources to best investigate this patient group. This study will collect a broad array of specialized neurologic testing in this group who, despite recovering from the acute SARS-CoV-2 infection, continue to experience neurological symptoms. It is hypothesized that this group will have abnormalities on neurologic testing that may identify discrete phenotypes of COVID-19 sequelae. Additionally, by including a group of individuals who have fully recovered without residual neurological symptoms, this study should be able to determine if there are abnormal results of study procedures in the absence of symptoms.

Pre-screening for this study will be done under the study, Post-Coronavirus Disease 19 Syndrome at the National Institutes of Health. Potentially eligible participants will be identified under the screening arm of that study and will be referred to the study team. If deemed eligible for this study based on a review of available records and a telephone discussion with the potential participant, participants may enroll. Enrollment will include a visit to the NIH Clinical Center for informed consent and completion of the study procedures. We anticipate that the baseline study procedures will take approximately 2-3 outpatient visits to complete or the participant may be admitted as an inpatient. Participants may return for an optional follow-up visit (with a repeat of the study procedures done initially) after at least 6 months from completion of their baseline study visit testing.

Objectives:

Primary Objective: To investigate structural brain MRI in those with prior SARS-CoV-2 infection and persistent neurologic symptoms and in those with prior SARS-CoV-2 infection without persistent neurologic symptoms.

Secondary objective:To investigate other components of neurologic function in those with prior SARS-CoV-2 infection and persistent neurologic symptoms and in those with prior SARS-CoV-2 infection and without persistent neurologic symptoms.

Endpoints: Primary endpoint: The number and character of brain MRI abnormalities on a dedicated research MRI protocol optimized to detect COVID-19-associated disease.

Secondary endpoints:

  1. Neurologic examination: The number and character of abnormalities associated with both central and peripheral nervous system disease.
  2. Autonomic testing: The number and character of test results indicating autonomic nervous system or catecholaminergic dysfunctions as evidenced by abnormal physiological or neurochemical measures at rest or in response to the Valsalva maneuver or head-up tilting.

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Study Type : Observational
Estimated Enrollment : 200 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: An Observational Study of Neurologic Function After COVID -19 Infection
Actual Study Start Date : October 28, 2020
Estimated Primary Completion Date : October 30, 2022
Estimated Study Completion Date : October 31, 2022

Resource links provided by the National Library of Medicine


Group/Cohort
Fully Recovered Individuals
Individuals with history of Covid-19 infection who have fully recovered without residual neurological symptoms
Patients with neuro-PASC
Patients with history of Covid-19 infection and persistent neurological symptoms (Post-Acute Sequelae of SARS CoV-2 Infection, neuro-PASC)



Primary Outcome Measures :
  1. MRI brain [ Time Frame: NIH Clinical Center Visit ]
    The number and character of brain MRI abnormalities on a dedicated research MRI protocol optimized to detect Covid-19-associated disease.


Secondary Outcome Measures :
  1. Neurological Examination [ Time Frame: NIH Clinical Center Visit ]
    Neurologic examination: The number and character of abnormalities associated with both central and peripheral nervous system disease.

  2. Autonomic Testing [ Time Frame: NIH Clinical Center Visit ]
    Autonomic testing: The number and character of test results indicating autonomic nervous system disease as evidenced by abnormal heart rate and blood pressure responses during tilt table testing.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Community Sample
Criteria
  • INCLUSION CRITERIA:

In order to be eligible to participate in the PASC cohort, an individual must meet all of the following criteria:

  1. Stated willingness to comply with all study procedures and availability for the duration of the study
  2. Male or female, aged at least 18 years at the time of enrollment
  3. Enrolled in the screening phase of Protocol 000089 Post-Coronavirus Disease 19 Convalescence at the National Institutes of Health
  4. Positive COVID-19 test result (per the methodology used for inclusion in Protocol 000089) at least six weeks prior to enrollment and exhibiting persistent neurologic symptoms evidenced by a positive response to at least one of the following:

    1. Do you have ongoing issues with being lightheaded or dizzy and if so, are these issues made worse when you sit or stand up

      quickly?

    2. Do you have ongoing issues with gait instability, problems with vision, speech, swallowing?
    3. Do you have ongoing issues with sensation or strength in your face/arms/legs?
  5. Ability of subject to understand and the willingness to sign a written informed consent document.

In order to be eligible to participate in the Fully Recovered cohort, an individual must meet all of the following criteria:

  1. Stated willingness to comply with all study procedures and availability for the duration of the study
  2. Male or female, aged at least 18 years at the time of enrollment
  3. Enrolled in the screening phase of Protocol 000089 Post-Coronavirus Disease 19 Convalescence at the National Institutes of Health
  4. Positive COVID-19 test result (per the methodology used for inclusion in Protocol 000089) in at least six weeks prior to enrollment.
  5. A self-reported illness narrative of recovery to prior health after a SARS/CoV2 infection, without residual fatigue, brain fog, orthostatic intolerance, or exercise intolerance.
  6. Ability of subject to understand and the willingness to sign a written informed consent document.

EXCLUSION CRITERIA:

An individual who meets any of the following criteria will be excluded from participation in this study:

  1. Presence of a contraindication to research 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 oral dose of a benzodiazepine.
  2. Contraindication to a research lumbar puncture, including use of anticoagulant medication, platelets < 50,000/microL, PT or PTT >1.5 x ULN for the NIH Clinical Center, or otherwise inability to complete the procedure.
  3. Contraindication to autonomic testing, including refractory ventricular arrhythmias or symptomatic coronary artery disease.
  4. A condition prior to the diagnosis of COVID-19 infection that would significantly confound interpretation of the research tests (e.g., prior diagnosis of postural orthostatic tachycardia syndrome), as determined by the study investigators.
  5. Fever or respiratory symptoms in the last seven days.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04564287


Contacts
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Contact: Janna Gelsomino, R.N. (301) 435-5166 janna.gelsomino@nih.gov
Contact: Avindra Nath, M.D. (301) 496-1561 natha@mail.nih.gov

Locations
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United States, Maryland
National Institutes of Health Clinical Center Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)    800-411-1222 ext TTY8664111010    prpl@cc.nih.gov   
Sponsors and Collaborators
National Institute of Neurological Disorders and Stroke (NINDS)
Investigators
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Principal Investigator: Avindra Nath, M.D. National Institute of Neurological Disorders and Stroke (NINDS)
Additional Information:
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Responsible Party: National Institute of Neurological Disorders and Stroke (NINDS)
ClinicalTrials.gov Identifier: NCT04564287    
Other Study ID Numbers: 10000094
000094-N
First Posted: September 25, 2020    Key Record Dates
Last Update Posted: June 24, 2022
Last Verified: June 10, 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by National Institutes of Health Clinical Center (CC) ( National Institute of Neurological Disorders and Stroke (NINDS) ):
Neurological
COVID-19
Coronavirus
Autonomic
Brain
Natural History
Additional relevant MeSH terms:
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COVID-19
Infections
Respiratory Tract Infections
Pneumonia, Viral
Pneumonia
Virus Diseases
Coronavirus Infections
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Lung Diseases
Respiratory Tract Diseases