Protocol for Assistance to Patients With Long Covid-19 Undergoing Treatment With HD-tDCS

Study Overview
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Brief Summary
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COVID-19 is an infectious disease which presents a heterogenous clinical presentation. Recent investigations suggest that people who were infected by COVID-19 often develop physical disabilities (i.e. pain, fatigue) and neurological complications after hospital discharge. Many therapeutic approaches such as transcranial direct current stimulation high definition (HD-tDCS) have been proposed to minimize functional and structural impairments. Recently, I electroencephalogram (EEG) has been used as predictor of HD-tDCS effectiveness in diverse neurological populations. However, evidences about this tool utilization as efficacy predictor of tDCS in COVID-19 people rest inconclusive. Thereby, our objective is to evaluate HD-tDCS efficacy on fatigue, pain and functional capacity of patients with COVID-19 chronic.

Detailed Description
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We propose a sham-controlled randomized clinical trial with patients in COVID-19 chronic. They will be evaluated according to following eligibility criteria : Patients who had a medical diagnosis of COVID-19, clinically stable, able to respond to simple commands, able to walk for six minutes and who sign study consent form will be enrolled. Those who present associated neurological diseases, pregnant, users of psychoactive drugs, patients who have metallic implants, electronic devices, pacemakers, or epileptic patients will be excluded. Patients will be allocated randomly to the experimental group or sham control. Sessions for experimental group consist of anodal HD-tDCS on Left diaphragmatic primary motor cortex associated to respiratory training (10 sessions, 3mA, 20 minutes/session). In the sham condition, the device provided a 30-second ramp-up period to the full 3 mA, followed immediately by a 30-second ramp down. Patients will be assessed in three moments: pre-treatment, post-treatment and after 30 days treatment ending (follow-up).

Official Title
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Protocol for Assistance to Patients With Long Covid-19 Undergoing Treatment With HD-tDCS

Conditions
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Coronavirus, COVID-19 Respiratory Infection

Intervention / Treatment
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* Device: Experimental group/ Active HD-tDCS
* Device: Control Group / Sham Group


Participation Criteria
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Eligibility Criteria
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Patients who had a medical diagnosis of COVID-19, clinically stable, able to respond to simple commands, able to walk for six minutes and who sign study consent form will be enrolled. Those who present associated neurological diseases, pregnant, users of psychoactive drugs, patients who have metallic implants, electronic devices, pacemakers, or epileptic patients will be excluded.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental Group/ Active HD-tDCS<br>Patients who will be randomly enrolled in this group. They will receive 10 sessions of anodal stimulation on cortical representation zone of left diaphragmatic motor cortex using HD-tDCS associated to respiratory training; for 20 minutes (each session) with a 3mA intensity. The electrical current will be delivered with a ramp-up time of 30 s, held at 3mA for 20 min, and then ramped down over 30 s. | Device: Experimental group/ Active HD-tDCS<br>* Patients enrolled in this group will received 20 minutes of anodal HD-tDCS ( tDCS 1x1, developed by Soterix Medical Inc.) during 10 sessions. It will be delivered a 3mA intensity electrical current accordingly 10/20 International System on cortical representation zone of left diaphragmatic motor cortex using HD-tDCS.<br>|
| Sham Comparator: Control Group / Sham Group<br>Patients enrolled in this group condition will receive 10 sessions of anodal stimulation on cortical representation zone of left diaphragmatic motor cortex using HD-tDCS associated to respiratory training; for 20 minutes (each session) with a 3mA intensity. In the sham condition, the device will provide a 30-second ramp-up followed immediately by a 30-second ramp down. | Device: Control Group / Sham Group<br>* 10-sessions of anodal HD-tDCS( tDCS 1x1, developed by Soterix Medical Inc.) associated to respiratory training; for 20 minutes (each session) with a 3mA intensity.The device will provide a 30-second ramp-up followed immediately by a 30-second ramp down.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fatigue Impact | MFIS-BR is a tool composed by 21 items stratified into 3 domains | From date of randomization (1 week before intervention beginning) up to 5 weeks (T1) and up to 10 weeks (T2; follow-up) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain Level | Pain level will be evaluated through McGill questionnaire. | From date of randomization (1 week before intervention beginning) up to 5 weeks (T1) and up to 10 weeks (T2; follow-up) | 
| Functional Capacity | Functional capacity will be evaluated by Lawton and Brody scale and also by 6 minutes walking test. | From date of randomization (1 week before intervention beginning) up to 5 weeks (T1) and up to 10 weeks (T2; follow-up) | 
| Quality of Life | Quality of life will be measured through Brazilian version of World Health Organization Quality of Life. | From date of randomization (1 week before intervention beginning) up to 5 weeks (T1) and up to 10 weeks (T2; follow-up) | 
| Pulmonary Function | This outcome will be assessed through spirometry, assessment of maximal inspiratory pressure and respiratory endurance. | From date of randomization (1 week before intervention beginning) up to 5 weeks (T1) and up to 10 weeks (T2; follow-up) | 
| Body Composition | Body composition analysis will be carried out by bioelectrical impedance analysis. | From date of randomization (1 week before intervention beginning) up to 5 weeks (T1) and up to 10 weeks (T2; follow-up) | 
| Anxiety | Anxiety level will be evaluated through Hamilton Anxiety Rating Scale. | From date of randomization (1 week before intervention beginning) up to 5 weeks (T1) and up to 10 weeks (T2; follow-up) | 
| Depression | Depression will be assessed by Beck's Depression Inventory. | From date of randomization (1 week before intervention beginning) up to 5 weeks (T1) and up to 10 weeks (T2; follow-up) | 
| Self-efficacy | Self-efficacy will be evaluated through the Self-efficacy manage chronic disease 6-item scale. | Self-efficacy will be assessed after intervention ending. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COVID-19 Respiratory Infection, Transcranial direct current stimulation, Non-invasive brain stimulation, Electroencephalography, Long Covid