Treatment of COVID-19 Post-acute Cognitive Impairment Sequelae With tDCS

NCT05389592 | Completed DMC

• 1 other identifier: 52917821.1.0000.0068
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

After almost 2 years of pandemic, the consequences of the post-COVID syndrome, or PASC (Post Acute-Sequelae of Sars-CoV-2), have become a major challenge in the management of affected patients, generating costs for health services. and insecurity regarding treatments for the sequelae, given the complex and still poorly understood pathophysiology of COVID-19. This troubling scenario raises important questions about the impact of COVID-19 on central nervous system sequelae, including the risk of cognitive decline in old age and progression to dementia. Therefore, studies that propose the possibility of treatment for this new clinical condition and that are free from systemic side effects, such as transcranial direct current stimulation (tDCS) and cognitive treatment, are extremely important in the face of this scenario. In addition, the evaluation of the neural mechanisms underlying the cognitive alterations of the PASC syndrome and after the treatment using multimodal magnetic resonance imaging (MRI) becomes relevant in view of the lack of studies related to the topic. Therefore, the objective of this double-blind randomized clinical trial is to assess whether tDCS associated with cognitive training can improve symptoms in patients with persistent cognitive deficits that started between 1 and 6 months after the resolution of acute COVID-19 infection (PASC) compared to the sham (placebo) group, in addition to exploring the structural, microstructural, functional and modeled electric field changes associated with cognitive alterations due to PASC syndrome and tDCS combined with cognitive treatment. 60 patients aged between 18 and 70 years and with a positive diagnosis of mild to moderate COVID-19 in the last 6 months in relation to the time of entry into the study will be recruited. All of them will be pre-screened online and in person to confirm the cognitive dysfunction associated with PASC.

Conditions

Cognitive Impairment; Post-Acute Sequelae of SARS-CoV-2 Infection; COVID-19

Outcome Measures

Primary Outcomes (1)

• Change in neuropsychological assessment between experimental groups

  A battery of neuropsychological tests to assess memory, attention, executive functions and mood.

  Week 0 (baseline) and Week 4 (endpoint)

Secondary Outcomes (3)

• Change in pupillary reflex

  Week 0 (baseline) and Week 4 (endpoint)

• Brain changes using multimodal magnetic resonance imaging (MRI)

  Week 0 (baseline)

• Change in heart rate variability (HRV) between experimental groups

  Week 0 (baseline) and Week 4 (endpoint)

Study Arms (2)

Double-active

EXPERIMENTAL

Active transcranial electrical stimulation and cognitive training.

Procedure: Active tDCS and cognitive training

Cognitive training-only

SHAM COMPARATOR

Sham transcranial electrical stimulation and cognitive training.

Procedure: Sham tDCS and cognitive training

Interventions

Active tDCS and cognitive training PROCEDURE

Electrical stimulation is delivered by the Soterix device, consisting of a one-size-fits-all, transcranial direct current stimulation headset with square electrodes. The anode is positioned over the left prefrontal cortex, and the cathode over the right prefrontal cortex. Current strenght is set at 2mA for 20 minutes, daily for 5 continuous days (with a 2-day pause) for 4 weeks. Cognitive training consists of a series of tasks performed in the BrainHQ app, which aim to stimulate the impaired cognitive domains in people with PASC. The cognitive training sessions are performed concomitantly to the tDCS sessions.

Double-active

Sham tDCS and cognitive training PROCEDURE

Sham electrical stimulation is delivered by the Soterix device, consisting of a one-size-fits-all, transcranial direct current stimulation headset with square electrodes. The anode is positioned over the left prefrontal cortex, and the cathode over the right prefrontal cortex. The sham protocol consists of a fade-in and fade-out phases of 1mA for 45 seconds, followed by a silent period in between for the remaining session time. Cognitive training consists of a series of tasks performed in the BrainHQ app, which aim to stimulate the impaired cognitive domains in people with PASC. The cognitive training sessions are performed concomitantly to the tDCS sessions.

Cognitive training-only

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age from 18 to 70 years;
• Positive diagnosis (confirmed by RT-PCR nasal swab) of COVID-19 within the last 6 months in relation to the time of assessment;
• Mild to moderate COVID-19 disease (no hospital stay required);
• A score above 10 in the cognitive symptoms domain of the Post-COVID-19 Symptom Assessment Questionnaire;
• Clinical neuropsychological assessment/neurological examination indicating cognitive impairment after acute COVID illness.

You may not qualify if:

• Contraindications to the use of tDCS (such as metal plates on the head);
• Severe acute COVID-19 illness;
• Less than 8 years of schooling;
• Presence of serious neurological conditions such as neurocognitive disorders, stroke, lacunar infarction, cerebral atrophy and others;
• Presence of serious psychiatric disorders, such as untreated mood disorders (including suicidal ideation), personality disorders, or psychotic disorders;
• Unstable clinical conditions;
• Use of medications (such as benzodiazepines and anticonvulsants) that can impair cognition;
• Presence of pathological neuroimaging findings (eg, acute or subacute lacunar or hemorrhagic stroke and others);
• Presence of a pacemaker, orthosis or prosthesis incompatible with the performance of magnetic resonance imaging;
• Claustrophobia.

Sponsors & Collaborators

• University of Sao Paulo: lead
• Fundação de Amparo à Pesquisa do Estado de São Paulo: collaborator

Study Sites (1)

Instituto de Psiquiatria

São Paulo, Brazil

Location

Related Publications (7)

• Charvet L, Shaw M, Dobbs B, Frontario A, Sherman K, Bikson M, Datta A, Krupp L, Zeinapour E, Kasschau M. Remotely Supervised Transcranial Direct Current Stimulation Increases the Benefit of At-Home Cognitive Training in Multiple Sclerosis. Neuromodulation. 2018 Jun;21(4):383-389. doi: 10.1111/ner.12583. Epub 2017 Feb 22.

  PMID: 28225155 BACKGROUND

• Charvet LE, Yang J, Shaw MT, Sherman K, Haider L, Xu J, Krupp LB. Cognitive function in multiple sclerosis improves with telerehabilitation: Results from a randomized controlled trial. PLoS One. 2017 May 11;12(5):e0177177. doi: 10.1371/journal.pone.0177177. eCollection 2017.

  PMID: 28493924 BACKGROUND

• Eilam-Stock T, George A, Charvet LE. Cognitive Telerehabilitation with Transcranial Direct Current Stimulation Improves Cognitive and Emotional Functioning Following a Traumatic Brain Injury: A Case Study. Arch Clin Neuropsychol. 2021 Apr 21;36(3):442-453. doi: 10.1093/arclin/acaa059.

  PMID: 33885138 BACKGROUND

• Kim PH, Kim M, Suh CH, Chung SR, Park JE, Kim SC, Choi YJ, Lee JH, Kim HS, Baek JH, Choi CG, Kim SJ. Neuroimaging Findings in Patients with COVID-19: A Systematic Review and Meta-Analysis. Korean J Radiol. 2021 Nov;22(11):1875-1885. doi: 10.3348/kjr.2021.0127. Epub 2021 Jul 1.

  PMID: 34269530 BACKGROUND

• Dedoncker J, Brunoni AR, Baeken C, Vanderhasselt MA. A Systematic Review and Meta-Analysis of the Effects of Transcranial Direct Current Stimulation (tDCS) Over the Dorsolateral Prefrontal Cortex in Healthy and Neuropsychiatric Samples: Influence of Stimulation Parameters. Brain Stimul. 2016 Jul-Aug;9(4):501-17. doi: 10.1016/j.brs.2016.04.006. Epub 2016 Apr 12.

  PMID: 27160468 BACKGROUND

• Baptista AF, Baltar A, Okano AH, Moreira A, Campos ACP, Fernandes AM, Brunoni AR, Badran BW, Tanaka C, de Andrade DC, da Silva Machado DG, Morya E, Trujillo E, Swami JK, Camprodon JA, Monte-Silva K, Sa KN, Nunes I, Goulardins JB, Bikson M, Sudbrack-Oliveira P, de Carvalho P, Duarte-Moreira RJ, Pagano RL, Shinjo SK, Zana Y. Applications of Non-invasive Neuromodulation for the Management of Disorders Related to COVID-19. Front Neurol. 2020 Nov 25;11:573718. doi: 10.3389/fneur.2020.573718. eCollection 2020.

  PMID: 33324324 BACKGROUND

• Vidal KS, Cavendish BA, Goerigk S, Pita Batista M, Oliveira Lima AR, Pinto BS, Neto Domingos AA, de Sousa JP, Pelosof R, Bertola L, Silva V, Suemoto CK, Razza LB, Bikson M, Pilloni G, Charvet L, Silva PHR, Brunoni AR. Transcranial direct current stimulation plus cognitive training for cognitive symptoms in patients with post-acute sequelae of SARS-CoV-2 infection: A randomized, double-blind, sham-controlled trial. Brain Stimul. 2025 Sep-Oct;18(5):1608-1616. doi: 10.1016/j.brs.2025.08.018. Epub 2025 Aug 21.

  PMID: 40848897 DERIVED

MeSH Terms

Conditions

Cognitive Dysfunction; Post-Acute COVID-19 Syndrome; COVID-19

Interventions

Cognitive Training

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders; 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

Intervention Hierarchy (Ancestors)

Neurological Rehabilitation; Rehabilitation; Aftercare; Continuity of Patient Care; Patient Care; Therapeutics; Health Services; Health Care Facilities Workforce and Services

Study Officials

• André R Brunoni, MD, PhD

  University of Sao Paulo

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of the Medical School of the University of Sao Paulo (FMUSP), Principal Investigator

Study Record Dates

• First Submitted: May 19, 2022
• First Posted: May 25, 2022
• Study Start: June 30, 2022
• Primary Completion: November 30, 2022
• Study Completion: March 30, 2023
• Last Updated: August 27, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

BR (1)