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NCT Number: NCT07278388

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

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.

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Key information

Conditions

PASC Post Acute Sequelae of COVID 19 COVID-19 Chronic Disease Coronaviridae Infections Coronavirus Infections Disease Attributes Fatigue Infections Lung Diseases Nidovirales Infections Pathologic Processes Pathological Conditions, Signs and Symptoms Pneumonia Pneumonia, Viral Post-Acute COVID-19 Syndrome Post-Infectious Disorders RNA Virus Infections Respiratory Tract Diseases Respiratory Tract Infections Signs and Symptoms Virus Diseases

Age range

18 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Kennedy Krieger Institute

Baltimore, Maryland, 21201, United States

Location status: Recruiting

Location contact

Anthony Gonzalez

CONTACT

[email protected]

443-923-2716

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Physical Fatigue

Behavioral

Participants will perform a physically demanding task (grip force exertion task) repeatedly to induce physical fatigue.

Primary outcomes

  1. 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.

  2. 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.

  3. 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.

  4. 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).

  5. 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'.

  6. 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.

  7. 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.

  8. 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).

  9. 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.

  10. 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'.

  11. 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.

  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.

Study contacts

Contact information is provided by the study sponsor or research team.

Anthony Gonzalez

CONTACT

[email protected]

443-923-2716

Vikram Chib, PhD

CONTACT

Sponsors and collaborators

Lead sponsor

Hugo W. Moser Research Institute at Kennedy Krieger, Inc.

Other

Collaborators

  • National Institute of Neurological Disorders and Stroke (NINDS)

Registry information

Official study title

Motivated Decision-Making and Performance

Important dates

Study start
2025
Primary completion
2029
Study completion
2029
First posted
Dec 12, 2025
Registry last updated
Dec 12, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

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This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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