Magnetic Resonance Analysis of Neural Inflammatory Factors and External Stimulation (MANIFEST)

July 11, 2025 updated by: University of New Mexico

Magnetic Resonance Analysis of Neural Inflammatory Factors and External Stimulation (MANIFEST)

The goal of this clinical trial is to test whether a type of rapid outpatient brain stimulation that uses magnetic fields, called accelerated intermittent theta burst stimulation (iTBS), can treat symptoms such as brain fog, depression, and anxiety in patients with Long COVID. The main questions it aims to answer are:

  • Is iTBS effective and feasible for reducing Long COVID symptoms? We will measure these symptoms using the Symptom Burden Questionnaire.
  • Are there changes in inflammatory brain chemicals associated with treatment with iTBS? We will be looking at levels of choline in the brain, which is thought to be related to inflammation.

Researchers will compare sham versus active forms of iTBS to see if the active group has greater improvement in symptoms.

Participants will complete symptom surveys, cognitive tests, and magnetic resonance imaging scans at the beginning, middle, and end of treatment.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Chronic neuropsychiatric symptoms of post-acute sequelae of COVID-19 (neuro-PASC) can lead to disability, loss of function, and reduced quality of life, but there are currently no validated effective treatments. We propose a randomized sham-controlled trial of "Magnetic Resonance Analysis of Neural Inflammatory Factors and External Stimulation (MANIFEST)." We will deliver active or sham accelerated iTBS (5x/day, 10 days, 25 blinded sessions followed by 25 open-label sessions) to each participant's brain target. We will assess neuro-PASC symptoms, mood, anxiety, cognition, and quality of life from baseline to end-of-treatment. We will correlate symptom improvement with clinical and imaging variables.

Study Type

Interventional

Enrollment (Estimated)

60

Phase

  • Phase 2

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 Locations

  • United States
    • New Mexico
      • Albuquerque, New Mexico, United States, 87106
        • Recruiting
        • University of New Mexico Health Science Center
        • Principal Investigator:
          • Davin Quinn, MD
        • Contact:

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

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. aged 18-80
  2. a documented diagnosis of PASC with evidence of ongoing symptoms as demonstrated by score of 12 on the NIH RECOVER Symptom List
  3. have "brain fog" or cognitive difficulties as one of the ongoing symptoms
  4. are fluent in English
  5. if taking psychotropic medications, have been on stable doses for the past month.

Exclusion Criteria:

  1. a prior history of other neurological disease, or any history of seizures, so as to reduce risk of exacerbation of epilepsy or other neurological symptoms;
  2. history of a psychotic disorder, such as schizophrenia or bipolar disorder, so as to reduce risk of psychiatric decompensation
  3. history of ongoing substance/alcohol dependence, to reduce confounding effects on diagnosis and brain imaging
  4. presence of any implanted electrical device (e.g., pacemaker), to reduce risk of device malfunction from rTMS
  5. recent medical hospitalization (within four weeks), to reduce risk of medical decompensation during the study
  6. any condition that would prevent the subject from completing the protocol
  7. appointment of a legal representative, to avoid coercion of a vulnerable population
  8. any ongoing litigation related to medical diagnosis, or disability, to prevent interference with legal proceedings
  9. any contraindication to MRI
  10. membership in an identified vulnerable population, including minors, pregnant women, and prisoners, so as to prevent coercion.

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: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Sham Comparator: Sham accelerated iTBS
Sham stimulation is delivered using the same coil as active stimulation, producing an equivalent sound, however it is shielded so that no effective magnetic field reaches the participant's brain. To blind participants to active versus sham condition, a mild electrical skin stimulation that has no brain effects is delivered simultaneously with iTBS at the scalp to both active and sham groups, creating the same sense of skin sensation in both groups.
Device: accelerated intermittent theta burst stimulation
Intermittent theta burst stimulation (iTBS), a FDA-approved form of noninvasive neuromodulation, can reduce neuropsychiatric symptoms and modulate inflammation in the thalamus as detected using dMRS, suggesting a potentially effective and efficient treatment approach with a pathophysiological component that is readily quantifiable.
Experimental: Active accelerated iTBS
Participants will be assigned to receive fMRI-guided iTBS (5 days, 5 sessions/day) to the left dorsolateral prefrontal cortex (dlPFC) during the sham-controlled phase. Each participant is invited to undergo 25 more sessions (5 more days) of open label, unblinded active accelerated fMRI-guided iTBS to the left dlPFC.
Device: accelerated intermittent theta burst stimulation
Intermittent theta burst stimulation (iTBS), a FDA-approved form of noninvasive neuromodulation, can reduce neuropsychiatric symptoms and modulate inflammation in the thalamus as detected using dMRS, suggesting a potentially effective and efficient treatment approach with a pathophysiological component that is readily quantifiable.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Aim 2
Time Frame: From baseline to end of treatment at 2 weeks
Identify neurometabolic and structural features associated with outcomes in MANIFEST. ADCcho in the thalamus measured using dMRS. The apparent diffusion coefficient of choline (ADCcho) is a measure of activity of microglia, higher values indicate higher levels of microglia. Decreased ADCcho means less microglia activation, and less inflammation.
From baseline to end of treatment at 2 weeks
Aim 1
Time Frame: From baseline to end of treatment at 2 weeks
Demonstrate that accelerated iTBS is effective and feasible for reducing neuro-PASC symptoms. Change in the score in the "Cognitive Function/Brain Fog Symptoms" score from the PACS: Post-acute COVID-19 Syndrome Questionnaire, where low scores are more severe symptoms compared to higher scores. Scale 1-Severly Unable to 4-Able. Higher scores show improvement in symptoms.
From baseline to end of treatment at 2 weeks

Collaborators and Investigators

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

Sponsor

University of New Mexico

Collaborators

United States Department of Defense
The Mind Research Network

Investigators

  • Principal Investigator: Davin Quinn, MD, University of New Mexico

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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)

July 7, 2025

Primary Completion (Estimated)

June 30, 2029

Study Completion (Estimated)

June 30, 2029

Study Registration Dates

First Submitted

April 2, 2025

First Submitted That Met QC Criteria

April 15, 2025

First Posted (Actual)

April 23, 2025

Study Record Updates

Last Update Posted (Actual)

July 15, 2025

Last Update Submitted That Met QC Criteria

July 11, 2025

Last Verified

July 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 24-470
  • HT9425-24-1-0742 (Other Grant/Funding Number: Department of Defense)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Demographics, symptoms, cognitive testing, and imaging data.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

product manufactured in and exported from the U.S.

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.

Clinical Trials on Long COVID

Clinical Trials on accelerated intermittent theta burst stimulation

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Mauritius

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe