Magnetic Resonance Analysis of Neural Inflammatory Factors and External Stimulation

Phase 2RecruitingNCT06940609

University of New Mexico60 enrolled

Overview

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.

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

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Eligibility

Sex: ALLMin age: 18 YearsMax age: 80 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

Aim 1

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.

Time frame: From baseline to end of treatment at 2 weeks

Aim 2

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.

Time frame: From baseline to end of treatment at 2 weeks

Magnetic Resonance Analysis of Neural Inflammatory Factors and External Stimulation

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Central Contacts