tDCS in the Management of Post-COVID Disorders

NCT06074848 | Recruiting Phase 2 DMC

• 1 other identifier: tDCS_COVID
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Long COVID

Keywords

Long COVID; Post-Acute COVID-19 Syndrome; Fatigue; Pain; Cognitive Dysfunction; Depression; Transcranial Direct Current Stimulation

Outcome Measures

Primary Outcomes (10)

• Fatigue - Modified Fatigue Impact Scale (MFIS)

  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.

  pre-intervention, 72 hours after the last intervention and 15 days after completion.

• Pain measure - Brief Pain Inventory (BPI)

  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

  pre-intervention, 72 hours after the last intervention and 15 days after completion.

• Pain measure - Visual Analog Scale (VAS)

  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.

  pre-intervention, 72 hours after the last intervention and 15 days after completion.

• Cognitive deficit - Montreal Cognitive Assessment Instrument (MoCA)

  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.

  pre-intervention, 72 hours after the last intervention and 15 days after completion.

• Cognitive deficit - FAS Test

  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.

  pre-intervention, 72 hours after the last intervention and 15 days after completion.

• Cognitive deficit - CFL Test

  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.

  pre-intervention, 72 hours after the last intervention and 15 days after completion.

• Cognitive deficit - Random Number Generator

  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.

  pre-intervention, 72 hours after the last intervention and 15 days after completion.

• Cognitive deficit - Digit span

  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.

  pre-intervention, 72 hours after the last intervention and 15 days after completion.

• Depressed mood - Hospital Anxiety and Depression Scale (HADS)

  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.

  pre-intervention, 72 hours after the last intervention and 15 days after completion.

• Depressed mood - Brunel Mood Scale (BRUMS)

  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.

  pre-intervention, 72 hours after the last intervention and 15 days after completion.

Secondary Outcomes (5)

• COVID clinical situation

  pre-intervention

• Level of physical activity

  pre-intervention

• State of strength and effort

  pre-intervention, 72 hours after the last intervention and 15 days after completion.

• Exercise capacity - 6-minute walk test

  pre-intervention, 72 hours after the last intervention and 15 days after completion.

• Immunometabolic evaluation

  pre-intervention and 72 hours after the last intervention

Study Arms (4)

Pain/fatigue tDCS real

EXPERIMENTAL

tDCS will be applied for 30 minutes (2 mA; 0.057 mA/cm²) during motor training. The anode will be positioned in the area referring to the left motor cortex (C3). The cathode will be positioned in the contralateral supraorbital region. Motor Training: the participant will be positioned on the mat where the initial 5 minutes will be warmed up with the target heart rate maintained at 50-60% of the maximum heart rate. The treadmill speed must be adjusted to keep the HR within the pre-established target range. At 5 minutes, Borg scale values, treadmill speed and HR should be recorded. The central 20 minutes will be considered the main part. For this, the target HR must be maintained between 64-76% of the maximum HR. Every 5 minutes (minutes 10, 15, 20 and 25) the values of the Borg scale, treadmill speed and HR must be recorded. In the final 5 minutes, the target HR must be kept below 60% of the maximum HR. Totaling 30 minutes of training on the treadmill.

Device: Transcranial Direct Current Stimulation (tDCS); Behavioral: Motor Training

Pain/fatigue tDCS sham

SHAM COMPARATOR

tDCS will be applied for 30 seconds (2 mA; 0.057 mA/cm²) during motor training. The anode will be positioned in the area referring to the left motor cortex (C3). The cathode will be positioned in the contralateral supraorbital region. Motor Training: the participant will be positioned on the mat where the initial 5 minutes will be warmed up with the target heart rate maintained at 50-60% of the maximum heart rate. The treadmill speed must be adjusted to keep the HR within the pre-established target range. At 5 minutes, Borg scale values, treadmill speed and HR should be recorded. The central 20 minutes will be considered the main part. For this, the target HR must be maintained between 64-76% of the maximum HR. Every 5 minutes (minutes 10, 15, 20 and 25) the values of the Borg scale, treadmill speed and HR must be recorded. In the final 5 minutes, the target HR must be kept below 60% of the maximum HR. Totaling 30 minutes of training on the treadmill.

Behavioral: Motor Training

Cognitive deficit and depressed mood tDCS real

EXPERIMENTAL

tDCS will be applied for 30 minutes (2 mA; 0.057 mA/cm²) during cognitive training. For volunteers with symptoms of depressed mood and/or cognitive impairment, the anode will be positioned in the area of the left dorsolateral prefrontal cortex (F3) and cognitive training will be performed. The cathode will be positioned in the contralateral supraorbital region. Cognitive Training: For cognitive training, performed during tDCS, a n-Back task will be performed online in the PsyToolkit (https://www.psytoolkit.org/). A previous study demonstrated the benefit of tDCS when combined with this cognitive training on working memory learning curves.

Device: Transcranial Direct Current Stimulation (tDCS); Behavioral: Cognitive Training

Cognitive deficit and depressed mood tDCS sham

SHAM COMPARATOR

tDCS will be applied for 30 seconds (2 mA; 0.057 mA/cm²) during cognitive training. For volunteers with symptoms of depressed mood and/or cognitive impairment, the anode will be positioned in the area of the left dorsolateral prefrontal cortex (F3) and cognitive training will be performed. The cathode will be positioned in the contralateral supraorbital region. Cognitive Training: For cognitive training, performed during tDCS, a n-Back task will be performed online in the PsyToolkit (https://www.psytoolkit.org/). A previous study demonstrated the benefit of tDCS when combined with this cognitive training on working memory learning curves.

Behavioral: Cognitive Training

Interventions

Transcranial Direct Current Stimulation (tDCS) DEVICE

tDCS deliver low-intensity electrical currents (2 mA) through electrodes placed on the scalp. It is used to influence brain function, modulating the neuronal activity in specific areas, in a non-invasive way, as the stimulation may not be perceived sensorially due to the low intensity. In some cases, it can provide mild tingling and bring minimal discomfort. It has the ability to increase or decrease the cortical excitability of neurons, influencing the polarization of neuronal membranes, with the anodal pole (positive) facilitating depolarization that results in increased neuronal excitability in the area, and the cathodal pole (negative) promoting a hyperpolarization of the neuronal resting membrane potential that reduces cortical excitability, used to inhibit activity in a particular cortical area.

Also known as: non-invasive brain stimulation, neuroConn (Germany)

Cognitive deficit and depressed mood tDCS real; Pain/fatigue tDCS real

Motor Training BEHAVIORAL

Motor training will be performed on the treadmill with the speed respecting the limits of the patient's maximum heart rate. To determine the maximum heart rate, the calculation must be performed: maximum heart rate = 208 - (0.7\*age). For participants who use beta-blockers, the following formula will be used: maximum heart rate = 164 - (0.7\*age). Just for the arms of fatigue and pain.

Pain/fatigue tDCS real; Pain/fatigue tDCS sham

Cognitive Training BEHAVIORAL

an n-Back task will be performed online at PsyToolkit (https://www.psytoolkit.org/). Just for the arms of cognitive impairment and depressed mood.

Cognitive deficit and depressed mood tDCS real; Cognitive deficit and depressed mood tDCS sham

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Universidade Federal de Pernambuco: lead
• São Paulo State University: collaborator

Study Sites (2)

Applied Neuroscience Laboratory-LANA

Recife, Pernambuco, 50740-560, Brazil

RECRUITING

Department of Physical Education, Faculty of Science and Technology

Presidente Prudente, São Paulo, 19060-900, Brazil

NOT YET RECRUITING

Related Links

• Choi, Hyo Jung, Dong Young Lee, et al. 2014. "A Normative Study of the Digit Span in an Educationally Diverse Elderly Population." Psychiatry Investigation 11 (1): 39-43.
• Dorneles, Gilson P., Paula C. Teixeira, et al. 2022. "Alterations in CD39/CD73 Axis of T Cells Associated with COVID-19 Severity." Journal of Cellula
• Lira, Pereira, and Guerra Minuzzi. "Functions in Adult Patients with Mild to Moderate SARS-CoV-2 Infections-A Protocol for an Observational Prospective Follow-Up Investigation: Fit-COVID-19." International Journal of High Risk Behaviors \& Addict. 2021
• Postiga, Isabelle A. L., Paula C., et al. "Systemic Redox Imbalance in Severe COVID-19 Patients." Cell Biochemistry and Function, August. 2022.
• Romão PR, Teixeira PC, Schipper L, et al. Viral load is associated with mitochondrial dysfunction and altered monocyte phenotype in acute severe SARS-CoV-2 infection. Int Immunopharmacol. 2022 Jul;108:108697. doi: 10.1016/j.intimp.2022.108697.
• Rossini, PM et al. 2015. "Non-Invasive Electrical and Magnetic Stimulation of the Brain, Spinal Cord, Roots and Peripheral Nerves: Basic Principles and Procedures for Routine Clinical and Research Application. An Updated Report from an IFCN Committee
• Scarpina, Federica, and Sofia Tagini. 2017. "The Stroop Color and Word Test." Frontiers in Psychology 8 (April): 557.
• Teixeira PC, Dorneles GP, Santana Filho PC, et al. Increased LPS levels coexist with systemic inflammation and result in monocyte activation in severe COVID-19 patients. Int Immunopharmacol. 2021 Nov;100:108125. doi: 10.1016/j.intimp.2021.108125.
• Versace, Viviana, Luca Sebastianelli, et al. 2021. "Intracortical GABAergic Dysfunction in Patients with Fatigue and Dysexecutive Syndrome after COVID-19." Clinical Neurophysiology: Official Journal of the Int Federation of Clinical Neurophysiol
• Yang, L., Liu, S., Liu, J. et al. COVID-19: immunopathogenesis and Immunotherapeutics. Sig Transduct Target Ther 5, 128 (2020)
• Organização Pan-Americana da Saúde. Plataforma Clínica Global da COVID-19 Ficha Clínica (Case Report Form - CRF) para quadro pós-COVID (Post COVID-19 CRF). OPAS-W/BRA/PHE/COVID-19/21-0025 (2021).

MeSH Terms

Conditions

Post-Acute COVID-19 Syndrome; Fatigue; Pain; Cognitive Dysfunction; Depression

Interventions

Transcranial Direct Current Stimulation; Cognitive Training

Condition Hierarchy (Ancestors)

COVID-19; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Post-Infectious Disorders; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Neurologic Manifestations; Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Electric Stimulation Therapy; Therapeutics; Convulsive Therapy; Psychiatric Somatic Therapies; Behavioral Disciplines and Activities; Electroshock; Psychological Techniques; Neurological Rehabilitation; Rehabilitation; Aftercare; Continuity of Patient Care; Patient Care; Health Services; Health Care Facilities Workforce and Services

Study Officials

• Patrícia Lopes, graduation

  Laboratory of Applied Neuroscience, Federal University of Pernambuco

  STUDY CHAIR

• Lívia Shirahige, PhD

  Laboratory of Applied Neuroscience, Federal University of Pernambuco

  STUDY CHAIR

• Bárbara Sousa

  Laboratory of Applied Neuroscience, Federal University of Pernambuco

  STUDY CHAIR

• Ana Cecília

  Laboratory of Applied Neuroscience, Federal University of Pernambuco

  STUDY CHAIR

• Adriana Baltar, PhD

  Laboratory of Applied Neuroscience, Federal University of Pernambuco

  STUDY CHAIR

• Rodrigo De Mattos, Master

  Laboratory of Applied Neuroscience, Federal University of Pernambuco

  STUDY CHAIR

• Gabriel Barreto, Master

  Laboratory of Applied Neuroscience, Federal University of Pernambuco

  STUDY CHAIR

• Fábio Santos de Lira, PhD

  Department of Physical Education, Faculty of Science and Technology - Presidente Prudente Campus

  STUDY CHAIR

• Fabrício Oliveira Souto, PhD

  Universidade Federal de Pernambuco

  STUDY CHAIR

• Kátia Monte-Silva, PhD

  Laboratory of Applied Neuroscience, Federal University of Pernambuco

  STUDY DIRECTOR

Central Study Contacts

Kátia Monte-Silva, PhD

CONTACT

+55 81 988631322; monte.silvakk@gmail.com

Patrícia Lopes, graduation

CONTACT

+55 81 999897661; patricia.flima@ufpe.br

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Investigador principal

Study Record Dates

• First Submitted: August 26, 2023
• First Posted: October 10, 2023
• Study Start: August 25, 2023
• Primary Completion: July 1, 2024
• Study Completion: September 28, 2024
• Last Updated: April 24, 2024

Record last verified: 2024-04

Locations

BR (2)