Blood-Brain Barrier Integrity and Immune Dynamics in Neuropsychiatric Sequelae of Post-SARS-CoV-2 Onset ME/CFS Versus Pre-Pandemic ME/CFS Patients (MECFS BBB)

June 9, 2026 updated by: Johns Hopkins University
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex chronic illness impacting multiple body systems and characterized by activity-limiting fatigue and post exertional symptom exacerbation, affecting over 3.5 million adults in the US and as many as half of those with long COVID. The mechanisms behind the frequently profound cognitive impairments in MECFS are elusive; however, disruption of the integrity of the blood brain barrier (BBB) and immune cell migration into the brain are thought to contribute to neuroinflammation and related neuropsychiatric burden in MECFS. This project combines brain imaging, neuropsychiatric assessments, and blood-based measures of inflammation in pre-pandemic and post-pandemic individuals with MECFS to understand the role of BBB permeability and inflammation as contributors to key aspects of cognition and mood.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Enrolling by invitation

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.

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.
Observational

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

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 Locations

  • United States
    • Maryland
      • Baltimore, Maryland, United States, 21297
        • Johns Hopkins Hospital

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

No

Sampling Method

Non-Probability Sample

Study Population

18-70 years of age

  • At least 8th grade education
  • Onset of the following symptoms prior to July 2019 (Pre-SARS-CoV-2 pandemic) and meeting 2015 IOM diagnostic criteria for MECFS:

Description

Inclusion Criteria:

  • Inclusion criteria for pre-pandemic onset ME/CFS cohort:
  • 18-70 years of age
  • At least 8th grade education
  • Onset of the following symptoms prior to July 2019 (Pre-SARS-CoV-2 pandemic) and meeting 2015 IOM diagnostic criteria for MECFS:
  • Substantial reduction in functioning and persistent and profound fatigue for at least 6 months. The person is unable to undertake the same level of activity before they became - . Their fatigue is not the result of significant exertion and is not substantially alleviated by rest.
  • Post-exertional malaise.
  • Unrefreshing sleep
  • At least one of the following two symptoms:
  • Cognitive impairment (difficulty with memory, finding words, understanding etc).
  • Orthostatic intolerance (symptoms like palpitations, sweating, dizziness, nausea when standing that are reduced or eliminated when lying down).

Inclusion criteria post SARS-CoV-2 onset ME/CFS:

  • 18-70 years of age
  • At least 8th grade education
  • Previous suspected, probable, or confirmed SARS-CoV-2 infection, as defined by the World Health Organization:
  • Suspected case of SARS-CoV-2 infection
  • Three options, A through C:

Meets the clinical OR epidemiological criteria.

  • Clinical criteria: Acute onset of fever AND cough (influenza-like illness) OR Acute onset of ANY THREE OR MORE of the following signs or symptoms: fever, cough, general, weakness/fatigue, headache, myalgia, sore throat, coryza, dyspnea, nausea, diarrhea, anorexia.
  • Epidemiological criteria: Contact of a probable or confirmed case or linked to a COVID-19 cluster; or B. Presents with acute respiratory infection with history of fever or measured fever of ≥ 38°C; and cough; with onset within the last 10 days; and who requires hospitalization) C. Presents with no clinical signs or symptoms, NOR meeting epidemiologic criteria with a positive professional use or self-test SARS-CoV-2 antigen-Rapid Diagnostic Test.
  • Probable case of SARS-CoV-2 infection, defined as meets clinical criteria above AND is a contact of a probable or confirmed case or is linked to a COVID-19 cluster.
  • Confirmed case of SARS-CoV-2 infection - Two options, i. and ii.:
  • A person with a positive nucleic acid amplification test, regardless of clinical criteria OR epidemiological criteria; or
  • Meeting clinical criteria AND/OR epidemiological criteria (See suspect case A). With a positive professional use or self-test SARS-CoV-2 Antigen-Rapid Diagnostic Test.
  • Post SARS CoV 2 onset of the following symptoms, meeting 2015 IOM diagnostic criteria for ME/CFS:
  • Substantial reduction in functioning and persistent and profound fatigue for at least 6 months. The person is unable to undertake the same level of activity before they became - - Their fatigue is not the result of significant exertion and is not substantially alleviated by rest.
  • Post-exertional malaise.
  • Unrefreshing sleep.
  • At least one of the following two symptoms:
  • Cognitive impairment (difficulty with memory, finding words, understanding etc).
  • Orthostatic intolerance (symptoms like palpitations, sweating, dizziness, nausea when standing that are reduced or eliminated when lying down).
  • Given that our application focuses on MECFS patients with neuropsychiatric symptoms the investigators will require participants to report >1 symptom with at least one of the symptoms being neuropsychiatric in nature (e.g., brain fog, anxiety, depression, headaches).

Exclusion both groups (pre-pandemic onset ME/CFS and post SARS-CoV-2 onset ME/CFS):

  • History of Axis I psychiatric disorders (including alcohol and drug dependence) except for mood disorders which developed after onset of ME/CFS symptoms.
  • Severe or unstable medical condition that would interfere with physical participation.
  • Neurological disorders, such as stroke, epilepsy, multiple sclerosis, Parkinson's disease, or dementia.
  • History of severe head injury that resulted in persistent traumatic brain injury sequelae.
  • Any condition that is contraindicated for the MRI environment (e.g., metal in the body, pacemaker, claustrophobia)
  • Currently pregnant.
  • Lack of English proficiency (to ensure validity in verbal outcome measures)
  • Active or recent (within 3 months) substance misuse (which is known to affect BBB permeability) assessed by clinical interview and toxicology (nicotine/cannabis allowed)
  • History of psychosis

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

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
Permeability Surface-Area Product (PS)
Time Frame: Up to 5 years
Investigate BBB permeability in MECFS patients using WEPCAST MRI as measured by Permeability Surface-Area Product (PS)
Up to 5 years
Inflammatory biomarkers levels
Time Frame: Up to 5 years
Inflammatory biomarkers levels and their relation to BBB or and its relationship to cognitive impairments
Up to 5 years

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.
Johns Hopkins University

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: Alba Azola, MD, Johns Hopkins University

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.
June 1, 2026

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 1, 2030

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 1, 2031

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 20, 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.
November 20, 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 1, 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.
June 11, 2026

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.
June 9, 2026

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.
June 1, 2026

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.
  • IRB00537228

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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