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| ID | Type | Description | Link |
|---|---|---|---|
| HT9425-24-1-0742 | Other Grant/Funding Number | Department of Defense |
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| Name | Class |
|---|---|
| The Mind Research Network | OTHER |
| United States Department of Defense | FED |
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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:
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Sham accelerated iTBS | Sham Comparator | 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. |
|
| Active accelerated iTBS | Experimental | 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| accelerated intermittent theta burst stimulation | Device | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 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. | From baseline to end of treatment at 2 weeks |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Crystal Garcia | Contact | 505-272-9552 | crabaca@salud.unm.edu |
| Name | Affiliation | Role |
|---|---|---|
| Davin Quinn, MD | University of New Mexico | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of New Mexico Health Science Center | Recruiting | Albuquerque | New Mexico | 87106 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 31930768 | Background | Genovese G, Marjanska M, Auerbach EJ, Cherif LY, Ronen I, Lehericy S, Branzoli F. In vivo diffusion-weighted MRS using semi-LASER in the human brain at 3 T: Methodological aspects and clinical feasibility. NMR Biomed. 2021 May;34(5):e4206. doi: 10.1002/nbm.4206. Epub 2020 Jan 13. | |
| 33779770 | Background | Schubert J, Tonietto M, Turkheimer F, Zanotti-Fregonara P, Veronese M. Supervised clustering for TSPO PET imaging. Eur J Nucl Med Mol Imaging. 2021 Dec;49(1):257-268. doi: 10.1007/s00259-021-05309-z. Epub 2021 Mar 29. |
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Demographics, symptoms, cognitive testing, and imaging data.
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| ID | Term |
|---|---|
| D000094024 | Post-Acute COVID-19 Syndrome |
| ID | Term |
|---|---|
| D000086382 | COVID-19 |
| D011024 | Pneumonia, Viral |
| D011014 | Pneumonia |
| D012141 | Respiratory Tract Infections |
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| D007239 |
| Infections |
| D014777 | Virus Diseases |
| D018352 | Coronavirus Infections |
| D003333 | Coronaviridae Infections |
| D030341 | Nidovirales Infections |
| D012327 | RNA Virus Infections |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D000094025 | Post-Infectious Disorders |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |