Long COVID, Long COVID-19 Syndrome, Long COVID Syndrome, PASC, PASC Post Acute Sequelae of COVID 19
Conditions
Brief summary
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.
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.
Interventions
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.
Sponsors
University of New Mexico
The Mind Research Network
United States Department of Defense
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Aim 1 | 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. |
| Aim 2 | 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. |
Countries
United States
Contacts
CONTACTCrystal Garcia
PRINCIPAL_INVESTIGATORDavin Quinn, MD
University of New Mexico
Outcome results
None listed