Transcranial Direct Current Stimulation as a Strategy for the Management of Disorders Generated by COVID-19: a Multicentric Study.
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 48
- 试验地点
- 4
- 主要终点
- Cognitive deficit - Digit span
研究概览
简要总结
Different physical and mental morbidities such as pain, fatigue, depressed mood and cognitive impairment can be triggered by coronavirus infection. Transcranial direct current stimulation (tDCS), an easy-to-apply, non-pharmacological and safe technique, has been used to attenuate these symptoms caused by other diseases, and, therefore, it is expected that it can also attenuate them when generated by COVID-19. It is known that the persistent inflammatory state observed after COVID-19 would be related to the progression of these negative symptoms. As non-invasive brain stimulation can also attenuate acute and persistent inflammation, it can be estimated that tDCS can be a useful tool to recover immune function and reduce post-COVID-19 morbidity.
详细描述
The aim of this study is to investigate if Direct Current Electrical Stimulation (tDCS) associated with motor and/or cognitive training is capable of reducing neuropsychiatric symptoms, as well as immune changes induced in COVID-19.
Volunteers will be randomized and allocated into four groups (Fatigue; Pain; Cognitive deficit and Depressed mood) and each group will be divided into two subgroups: 1) real tDCS + motor or cognitive training; and, 2) sham tDCS + motor or cognitive training according to each outcome. The volunteers will be evaluated in two aspect: immunometabolic evaluation (i) and clinical assessment (ii). The measures will pe performed in three moments: baseline (session 1); 72 hours after the last intervention (session 12) and follow up - 15 days after the last intervention (session 13).
(i) The immunometabolic evaluation will start with the participant's blood collection, after fasting for 8-12 hours, without having practiced intense physical activity and without drinking alcohol in the 24 hours prior to the collect. The blood will be allocated in 10 vacutainer tubes of 5ml containing EDTA for plasma separation, in 2 dry vacutainer tubes of 5ml for serum separation and 1 vacutainer tube of 5ml containing fluoride. In particular, 1 dry tube must rest for 1h, for subsequent BDNF analysis. 2 serum tubes, 2 plasma tubes and 1 fluoride tube should be centrifuged at 3,500 rpm for 15 minutes at 4°C, and the samples should be stored at -80°C for later analysis and the other fresh plasma tubes used (up to 2 hours after collection) for whole blood and PBMC stimuli.
Stimulation of whole blood with LPS, culture of peripheral blood mononuclear cells (PBMC), assessment of oxidative stress, assessment of adenine and LPS purine levels in plasma, analysis of immunophenotyping and apoptosis by flow cytometry, assessment of expression of purinoreceptors, mitochondrial assays in monocytes and T lymphocytes, evaluation of the generation of reactive oxygen species and quantification of several mediators by ELISA.
(ii) The clinical assessment will be performed using the following outcome measures:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Long COVID-19 (>3 months)
- •The presence of at least one of the following symptoms, after diagnosed SARS-COV-2 infection:
- •Persistent pain Fatigue Depressed mood Cognitive impairment
排除标准
- •Hemodynamic instability
- •Historic of use or abuse of drugs or alcohol
- •Use of medications that may interfere with the study results (anti-inflammatories and antibiotics)
- •Metallic implant in skull and face
- •Implant in the central nervous system
- •Pacemaker
结局指标
主要结局
Cognitive deficit - Digit span
时间窗: pre-intervention, 72 hours after the last intervention and 15 days after completion.
Used to assess the ability to focus, maintain attention, mental manipulation and memory. It consists of repeating the numbers said by the evaluator, where in the first phase they will be said in direct order (16 points) and in the second phase in reverse order (14 points). Together they add up to a maximum score of 30 points.
Fatigue - Modified Fatigue Impact Scale (MFIS)
时间窗: pre-intervention, 72 hours after the last intervention and 15 days after completion.
The MFIS is a scale that contains 21 items that analyze cognitive, physical and psychosocial issues. The physical domain allows scores from 0 to 36, the cognitive domain from 0 to 40 and the psychosocial domain from 0 to 8. The total MFIS score is given by the sum of the three domains and varies from 0 to 84 points. Values below 38 correspond to the absence of fatigue, and above this value, the higher the score, the greater the individual's degree of fatigue.
Cognitive deficit - CFL Test
时间窗: pre-intervention, 72 hours after the last intervention and 15 days after completion.
is a Verbal Fluency Test/Phonological Fluency Test that assesses verbal learning and the ability to produce words verbally. The total score is given by adding up all correct words starting with the three letters.
Cognitive deficit - Montreal Cognitive Assessment Instrument (MoCA)
时间窗: pre-intervention, 72 hours after the last intervention and 15 days after completion.
quickly identifies cognitive declines in patients with a maximum score of 30 (points), evaluates eight cognitive domains: 1. Executive function: with the Trail Making Test B (adapted - 1 point), phonemic verbal fluency (1 point) and abstraction verbal (2 points). 2. Visual-spatial ability: drawing the clock (3 points) and copying the cube (1 point). 3. memory: delayed recall of words 5 minutes (5 points). 4. Attention/5. Concentration/6. Working memory: digit memory (forward sense - 1 point), digit memory (backward sense - 1 point), sustained attention task (target detection - 1 point) and serial subtraction of 7 (3 points). 7. Language: naming 3 unfamiliar animals (3 points), repetition of 2 syntactically complex sentences - phonemic verbal fluency (above - 2 points). 8. Orientation: temporal (4 points) and spatial (2 points). It has a total score of 30 points. The cutoff score is 26 points, indicating the presence of cognitive deficit. Score above said is considered normal.
Depressed mood - Hospital Anxiety and Depression Scale (HADS)
时间窗: pre-intervention, 72 hours after the last intervention and 15 days after completion.
measures symptoms of anxiety and depression divided into an anxiety subscale (HADS-Anxiety) and a depression subscale (HADS-Depression). Each question has a variable score from zero to four points, with 14 questions in total. From 0 - 7 points indicates anxiety and depression unlikely; 8 - 11 points indicate possible anxiety and depression and 12 - 21 points indicate probable anxiety and depression.
Pain measure - Brief Pain Inventory (BPI)
时间窗: pre-intervention, 72 hours after the last intervention and 15 days after completion.
assesses severity of pain, impact of pain on daily functions, location of pain, analgesics, and amount of pain relief in the past 24 hours and past week on an 11-point scale ranging from 0 (no pain/no interference) to 10 (the worst possible). Including a body diagram to assess the location of pain (item 2), scores range from 0 to 10 and are calculated as the average of the total items. A high score represents a high pain intensity or pain interference
Pain measure - Visual Analog Scale (VAS)
时间窗: pre-intervention, 72 hours after the last intervention and 15 days after completion.
consiste em uma régua numerada de 0 a 10 e dividida em três partes, leve, moderada e intensa, com auxílio visual para facilitar a mensuração da intensidade da dor do paciente.
Cognitive deficit - Random Number Generator
时间窗: pre-intervention, 72 hours after the last intervention and 15 days after completion.
Assesses language and executive function. Numbers are produced randomly when a previously recorded sound signal is heard. You must speak numbers from 1 to 10 without speaking sequences.
Cognitive deficit - FAS Test
时间窗: pre-intervention, 72 hours after the last intervention and 15 days after completion.
is a Verbal Fluency Test/Phonological Fluency Test that assesses verbal learning and the ability to produce words verbally. The total score is given by adding up all correct words starting with the three letters.
Depressed mood - Brunel Mood Scale (BRUMS)
时间窗: pre-intervention, 72 hours after the last intervention and 15 days after completion.
Used to quickly measure a patient's mood using six subscales: tension, depression, anger, vigor, fatigue and confusion. It contains 24 questions that must be evaluated according to a scale of 0 to 4 points, each subscale has a score that can vary from 0 - 16.
次要结局
- State of strength and effort(pre-intervention, 72 hours after the last intervention and 15 days after completion.)
- Level of physical activity(pre-intervention)
- Exercise capacity - 6-minute walk test(pre-intervention, 72 hours after the last intervention and 15 days after completion.)
- COVID clinical situation(pre-intervention)
- Immunometabolic evaluation(pre-intervention and 72 hours after the last intervention)
研究者
Kátia Monte-Silva
Investigador principal
Universidade Federal de Pernambuco