Magnetic Resonance Analysis of Neural Inflammatory Factors and External Stimulation

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Устройство 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.

Первичные конечные точки

• Aim 1 [Срок оценки: From baseline to end of treatment at 2 weeks]
• Aim 2 [Срок оценки: From baseline to end of treatment at 2 weeks]

Критерии участия

Критерии включения

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

Критерии исключения

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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Перекрёстный дизайн

Маскирование

Двойное слепое

Основная цель

Лечение

Центры проведения

США · 1 центр

• University of New Mexico Health Science Center — Albuquerque

Публикации

• 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. PMID 31930768
• 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. PMID 33779770
• Ling JM, Klimaj S, Toulouse T, Mayer AR. A prospective study of gray matter abnormalities in mild traumatic brain injury. Neurology. 2013 Dec 10;81(24):2121-7. doi: 10.1212/01.wnl.0000437302.36064.b1. Epub 2013 Nov 20. PMID 24259552
• Mayer AR, Hanlon FM, Dodd AB, Ling JM, Klimaj SD, Meier TB. A functional magnetic resonance imaging study of cognitive control and neurosensory deficits in mild traumatic brain injury. Hum Brain Mapp. 2015 Nov;36(11):4394-406. doi: 10.1002/hbm.22930. Epub 2015 Aug 19. PMID 26493161
• Mayer AR, Yang Z, Yeo RA, Pena A, Ling JM, Mannell MV, Stippler M, Mojtahed K. A functional MRI study of multimodal selective attention following mild traumatic brain injury. Brain Imaging Behav. 2012 Jun;6(2):343-54. doi: 10.1007/s11682-012-9178-z. PMID 22673802
• Mayer AR, Toulouse T, Klimaj S, Ling JM, Pena A, Bellgowan PS. Investigating the properties of the hemodynamic response function after mild traumatic brain injury. J Neurotrauma. 2014 Jan 15;31(2):189-97. doi: 10.1089/neu.2013.3069. Epub 2013 Nov 20. PMID 23965000
• Davenport ND, Lim KO, Armstrong MT, Sponheim SR. Diffuse and spatially variable white matter disruptions are associated with blast-related mild traumatic brain injury. Neuroimage. 2012 Feb 1;59(3):2017-24. doi: 10.1016/j.neuroimage.2011.10.050. Epub 2011 Oct 20. PMID 22040736
• Davenport ND, Lamberty GJ, Nelson NW, Lim KO, Armstrong MT, Sponheim SR. PTSD confounds detection of compromised cerebral white matter integrity in military veterans reporting a history of mild traumatic brain injury. Brain Inj. 2016;30(12):1491-1500. doi: 10.1080/02699052.2016.1219057. PMID 27834537

Идентификаторы

NCT: NCT06940609 · 24-470 · HT9425-24-1-0742

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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