Neural Mechanisms of Fatigue in Post-Acute Sequela of SARS-CoV-2

December 1, 2025 updated by: Hugo W. Moser Research Institute at Kennedy Krieger, Inc.

Motivated Decision-Making and Performance

This proposal aims to understand the neurobiological mechanisms of fatigue in individuals with Post-Acute Sequelae of SARS-CoV-2 Infection (PASC). This knowledge will eventually provide candidate mechanisms to target with pharmacological intervention and inform rehabilitative care for those individuals suffering from symptoms of fatigue in PASC.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
200

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

  • Name: Vikram Chib, PhD

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • Age 18 to 75 years old.
  • Have received a clinical diagnosis of post-acute sequelae of SARS-CoV-2 (PASC)/long COVID syndrome using the criteria specified by Thaweethai, et al., 2023 (JAMA). This symptom checklist provides a score based on the number and severity of symptoms. An individual with a score >12 is classified as having PASC.
  • Currently experiencing Fatigue/Brain Fog as assessed with the Post-COVID symptom checklist and the PedsQL questionnaire.

Exclusion Criteria:

  • Neurological disorders including, but not limited to, stroke, head injury, epilepsy, seizures, brain tumors, brain surgery, Parkinson's Disease, or any other neuromuscular disease (self-report).
  • Diagnosed history of severe psychiatric diseases such as depression and schizophrenia (self-report).
  • Congestive heart failure.
  • Peripheral artery disease with claudication.
  • Cancer.
  • Pulmonary or renal failure.
  • Unstable angina.
  • Uncontrolled hypertension (more than 190/110 mmHg).
  • Severe aphasia.
  • Orthopedic or pain conditions.
  • Have had exposure to metal or metal implants, due to the hazardous effects of the magnetic field.
  • If on immunomodulatory therapy, they must have been on that therapy for at least 6 months before the start of the study.

Healthy age- and sex-matched controls for PASC - Exclusion criteria: Participants with a history of any of the following will be excluded from the study:

  • Hospitalization due to SARS-CoV-2 infection.
  • Neurological disorders including, but not limited to, stroke, head injury, epilepsy, seizures, brain tumors, brain surgery, Parkinson's Disease, or any other neuromuscular disease (self-report).
  • Diagnosed history of severe psychiatric diseases such as depression and schizophrenia (self-report).
  • Congestive heart failure.
  • Peripheral artery disease with claudication.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: PASC Participants - Physical Fatigue Task
Participants will perform a physically demanding task (grip force exertion task) repeatedly to induce physical fatigue.
Behavioral: Physical Fatigue
Participants will perform a physically demanding task (grip force exertion task) repeatedly to induce physical fatigue.
Experimental: Control Participants - Physical Fatigue Task
Participants will perform a physically demanding task (grip force exertion task) repeatedly to induce physical fatigue.
Behavioral: Physical Fatigue
Participants will perform a physically demanding task (grip force exertion task) repeatedly to induce physical fatigue.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Comparison between PASC and HC - difference in mean Assessment Error
Time Frame: Baseline, during experimental protocol.
The difference between the level of effort rated by participants, and their average grip force exerted on a grip force dynamometer. Compared between PASC and HC.
Baseline, during experimental protocol.
Comparing between PASC and HC - difference in BBB permeability
Time Frame: Baseline, during MRI acquisition.
Collected from and MRI sequence designed to measure BBB permeability.
Baseline, during MRI acquisition.
Comparing between PASC and HC - Regions of the brain that are sensitive to Assessment error as a function of disease state
Time Frame: Baseline, during experimental protocol.
We will examine an fMRI contrast, at the time of effort assessment, between HC and PASC groups. This contrast will examine percent signal change in brain activity.
Baseline, during experimental protocol.
The modulatory effect of BBB permeability on the relationship between Neural Activity and Effort Assessment
Time Frame: Baseline, during experimental protocol and MRI aquisition.
We will create a structural equation model that includes BBB permeability, fMRI activity, effort assessment behavior, and disease state (PASC/HC).
Baseline, during experimental protocol and MRI aquisition.
Comparing between PASC and HC - Difference in momentary subjective fatigue ratings
Time Frame: Baseline and during fatiguing exertions in the experimental protocol.
Measures of subjective fatigue will be collected on self report scale that ranges from 'not fatigued at all' to 'very fatigued'.
Baseline and during fatiguing exertions in the experimental protocol.
Comparing between PASC and HC - Difference in Mean Acceptance Rate of Risky Effort Options between rested/baseline and fatigue choices
Time Frame: Baseline and during fatiguing exertions in the experimental protocol.
Proportion of decisions in which inviduals choice to accept a risky effort opitions over a sure effort option.
Baseline and during fatiguing exertions in the experimental protocol.
Comparing between PASC and HC - Regions of the brain encoding a difference in effort cost between rested/baseline and fatigue choices
Time Frame: Baseline and during fatiguing exertions in the experimental protocol.
We will examine a contrast between chosen effort value pre versus post fatigue, between the HC and PASC groups. This contrast will examine percent signal change in brain activity.
Baseline and during fatiguing exertions in the experimental protocol.
The modulatory effect of BBB permeability on the relationship between Neural Activity and change effort-based decision-making
Time Frame: Baseline, fatigueing exertion, and during experimental protocol and MRI aquisition
We will create a structural equation model that includes BBB permeability, fMRI activity, change in effort-based decision-making, and disease state (PASC/HC).
Baseline, fatigueing exertion, and during experimental protocol and MRI aquisition
Comparing between PASC and HC - Difference in mean assessment error as a function of time
Time Frame: Data collections at months 0, 3, 6, 12
The difference between the level of effort rated by participants, and their average grip force exerted on a grip force dynamometer. Compared between PASC and HC.
Data collections at months 0, 3, 6, 12
Comparing between PASC and HC - Difference in momentary subjective fatigue ratings as a function of time
Time Frame: Data collections at months 0, 3, 6, 12
Measures of subjective fatigue will be collected on self report scale that ranges from 'not fatigued at all' to 'very fatigued'.
Data collections at months 0, 3, 6, 12
Comparing between PASC and HC - difference in BBB permeability as a function of time
Time Frame: Data collections at months 0, 3, 6, 12
Collected from and MRI sequence designed to measure BBB permeability.
Data collections at months 0, 3, 6, 12
Comparing between PASC and HC - Regions of the brain that are sensitive to Assessment error as a function of disease state and time
Time Frame: Data collections at months 0, 3, 6, 12
We will examine a contrast, at the time of effort assessment, between HC and PASC groups, and use time as a covariate. This contrast will examine percent signal change in brain activity.
Data collections at months 0, 3, 6, 12

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Hugo W. Moser Research Institute at Kennedy Krieger, Inc.

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Institute of Neurological Disorders and Stroke (NINDS)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Vikram Chib, PhD, Johns Hopkins University; Kennedy Krieger Institute

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 16, 2025

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 31, 2029

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 31, 2029

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 19, 2025

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 1, 2025

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 12, 2025

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
December 12, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 1, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • IRB00283000_1
  • R01NS140610 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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