Magnetic Resonance Analysis of Neural Inflammatory Factors and External Stimulation (MANIFEST)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 60
- 试验地点
- 2
- 主要终点
- Aim 1
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Double (Participant, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
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.
干预措施: accelerated intermittent theta burst stimulation (Device)
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.
干预措施: accelerated intermittent theta burst stimulation (Device)
结局指标
主要结局
Aim 1
时间窗: 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
时间窗: 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.
次要结局
未报告次要终点