NCT07154199

Brief Summary

This study aims to investigate whether a specific brain region mediates the cognitive deficit in long COVID brain fog, and whether targeted modulation of this region can improve cognition. In observational study, the objective was to identify potential intervention targets for patients with long COVID brain fog. A total of 120 patients with long COVID were enrolled. Brain fog (BF) severity was quantified using the Brain Fog Assessment (BFA). Participants completed a continuous random-dot motion (cRDM) task during 128-channel electroencephalography (EEG) and underwent structural MRI and standardized neuropsychological testing. In interventional study, 40 participants with persistent BF symptoms were enrolled for transcranial ultrasound stimulation (TUS). On Day 1, participants completed the BFA and provided demographic data, then performed the baseline cRDM task; 20 minutes later, structural MRI and baseline resting-state MRI were acquired. On Day 2, participants received 60 seconds of TUS (active or sham) according to randomized allocation. Twenty minutes post-stimulation, an 8-minute resting-state MRI scan was obtained, followed immediately by the follow-up cRDM task.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
40

participants targeted

Target at below P25 for not_applicable covid19

Timeline
19mo left

Started Jan 2023

Longer than P75 for not_applicable covid19

Geographic Reach
1 country

2 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress68%
Jan 2023Dec 2027

Study Start

First participant enrolled

January 6, 2023

Completed
2.6 years until next milestone

First Submitted

Initial submission to the registry

August 24, 2025

Completed
11 days until next milestone

First Posted

Study publicly available on registry

September 4, 2025

Completed
2.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2027

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2027

Last Updated

September 4, 2025

Status Verified

August 1, 2025

Enrollment Period

4.9 years

First QC Date

August 24, 2025

Last Update Submit

September 2, 2025

Conditions

Outcome Measures

Primary Outcomes (2)

  • false alarm rate change

    false alarm rate change

    Day 1, Day 2

  • accuracy change

    accuracy change

    Day 1, Day 2

Secondary Outcomes (6)

  • false alarm rate

    Day 1

  • accuracy

    Day 1

  • cRDM modeling metrics

    Day 1

  • Neural activation pattern of EEG

    Day 1

  • Brain structure indicator of MRI

    Day 1

  • +1 more secondary outcomes

Study Arms (2)

sham stimulation group

SHAM COMPARATOR

In the sham group, the transducer power was turned off, pre-recorded pulse repetition sounds were played to control for auditory confounds. The equipment appearance is consistent with the device. Single stimulation, 60 seconds.

Device: sham transcranial ultrasound stimulation

real TUS group

EXPERIMENTAL

Ultrasound stimulation was delivered using TPO-203 and H-104MR\_4AA-4CH transducer (Sonic Concepts, Woodinville, WA, USA). The target free-field spatial peak pulse-average intensity was maintained at 33.85 W/cm². The stimulation target is the right inferior Insula, according the results from observational study.

Device: real transcranial ultrasound stimulation

Interventions

In the sham group, the transducer power was turned off, pre-recorded pulse repetition sounds were played to control for auditory confounds. The equipment appearance is consistent with the test device. Single stimulation, 60 seconds.

sham stimulation group

Ultrasound stimulation was delivered using TPO-203 and H-104MR\_4AA-4CH transducer (Sonic Concepts, Woodinville, WA, USA). In the real stimulation group, theta-burst TUS (Yaakub et al., 2024; Yaakub et al., 2023) was performed with the following parameters: pulse duration = 20 ms; pulse repetition interval = 200 ms; total duration = 80 s. The target free-field spatial peak pulse-average intensity was maintained at 33.85 W/cm². The stimulation target was defined as the overlapping region between the source localisation results and the right inferior insula in the Destrieux atlas

real TUS group

Eligibility Criteria

Age18 Years - 75 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Patients should have a history of COVID-19 infection (positive test results for either polymerase chain reaction or rapid antigen test) and report persistent brain fog (BF) symptoms at least 4 weeks after recovering from acute COVID-19.

You may not qualify if:

  • \. Presence of any symptoms of cognitive impairment or other neurological symptoms prior to COVID-19 infection;
  • \. Structural MRI revealing significant intracranial lesions or structural abnormalities;
  • \. Development of severe neurological complications after COVID-19 infection, including delirium, cerebrovascular diseases, encephalitis, and epilepsy;
  • \. Other disorders that may cause cognitive impairment, including Dementia, Schizophrenia spectrum disorders, stroke, Alzheimer's disease, and Parkinson's disease.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

Xuanwu Hospital, Capital Medical University

Beijing, Beijing Municipality, 100053, China

RECRUITING

Shandong Daizhuang Hospital

Jining, Shandong, China

RECRUITING

MeSH Terms

Conditions

COVID-19Mental FatiguePost-Acute COVID-19 Syndrome

Condition Hierarchy (Ancestors)

Pneumonia, ViralPneumoniaRespiratory Tract InfectionsInfectionsVirus DiseasesCoronavirus InfectionsCoronaviridae InfectionsNidovirales InfectionsRNA Virus InfectionsLung DiseasesRespiratory Tract DiseasesFatigueSigns and SymptomsPathological Conditions, Signs and SymptomsBehavioral SymptomsBehaviorPost-Infectious DisordersChronic DiseaseDisease AttributesPathologic Processes

Study Officials

  • Yi Tang, MD., PhD

    Xuanwu Hospital, Beijing

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Yi Tang, MD., PhD

CONTACT

Shaojiong Zhou, MD.

CONTACT

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
PARTICIPANT
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

August 24, 2025

First Posted

September 4, 2025

Study Start

January 6, 2023

Primary Completion (Estimated)

December 1, 2027

Study Completion (Estimated)

December 1, 2027

Last Updated

September 4, 2025

Record last verified: 2025-08

Data Sharing

IPD Sharing
Will not share

Locations