Cognitive Training and Brain Stimulation in Patients With Post-COVID-19 Cognitive Impairment

Study Overview
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Brief Summary
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The aim of the study is to investigate effects of brain stimulation-assisted cognitive training in patients with persistent subjective or objective cognitive impairment after polymerase chain reaction (PCR)-positive COVID-19 disease.

Detailed Description
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Long-term persistent symptoms occur in a substantial number of patients diagnosed with coronavirus 2019 disease (COVID-19). First evidence suggests that long-term symptoms develop not only after severe courses of the disease, but also after less serious illness and include various symptoms such as fatigue and impaired memory, concentration or sleep. During recovery, these symptoms present a heavy burden for patients, who then often experience psychological distress and reduced quality of life. The goal of the present study is to assess the effects of cognitive training alone or in combination with tDCS on cognitive performance, quality of life and mental health in patients with subjective or objective cognitive impairments following post-COVID disease. Patients will either participate in a three-week cognitive training with concurrent online high-definition tDCS application or placebo (sham) tDCS or participate in an evidence-based muscle relaxation training combined with placebo tDCS. We hypothesize that cognitive training with sham or active tDCS will result in more pronounced improvement on a transfer task compared to the control group. We also hypothesize that training combined with anodal tDCS will lead to significantly higher performance on a transfer task than training combined with sham tDCS. Additionally, we will determine effects on specifically trained and other untrained cognitive functions immediately after the intervention as well as their maintenance one month later.

Official Title
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Neuromodulation Through Brain Stimulation-assisted Cognitive Training in Patients With Post-COVID-19 Cognitive Impairment

Conditions
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COVID-19, Post-COVID-19

Intervention / Treatment
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* Device: Anodal tDCS
* Device: Sham tDCS
* Behavioral: Intensive cognitive training
* Behavioral: Progressive muscle relaxation (PMR)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: History of COVID-19 condition at least 4-6 weeks prior to study inclusion Self-reported concerns regarding cognitive functioning. Age: 18-60 years. Exclusion Criteria: Acute COVID-19 illness. History of dementia before COVID-19. Other neurodegenerative neurological disorders; epilepsy or history of seizures. Severe and untreated medical conditions that preclude participation in the training, as determined by responsible physician. History of severe alcoholism or use of drugs. Severe psychiatric disorders such as severe depression (if not in remission) or psychosis. Contraindication to tDCS application (Antal et al. 2017).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Anodal tDCS + cognitive training<br>device: anodal transcranial direct current stimulation (tDCS), 9 sessions with 20 minutes stimulation each (2 mA) over left dorsolateral prefrontal cortex behavioral: intensive cognitive training intensive cognitive training of letter memory updating task (20 minutes), 9 sessions | Device: Anodal tDCS<br>* Anodal transcranial direct current stimulation (tDCS), 9 sessions with 20 minutes stimulation each (2 mA)<br>Behavioral: Intensive cognitive training<br>* Intensive cognitive training of a letter memory updating task, 9 sessions<br>|
| Placebo Comparator: Sham tDCS + cognitive training<br>device: sham transcranial direct current stimulation (tDCS), 9 sessions with 30 seconds stimulation each (2 mA) over left dorsolateral prefrontal cortex behavioral: intensive cognitive training intensive cognitive training of letter memory updating task (20 minutes), 9 sessions | Device: Sham tDCS<br>* Sham transcranial direct current stimulation (tDCS), 9 sessions with 30 sec stimulation each (2 mA) to ensure blinding of participants<br>Behavioral: Intensive cognitive training<br>* Intensive cognitive training of a letter memory updating task, 9 sessions<br>|
| Active Comparator: Sham tDCS + Progressive Muscle Relaxation training<br>device: sham transcranial direct current stimulation (tDCS), 9 sessions with 30 seconds stimulation each (2 mA) over left dorsolateral prefrontal cortex behavioral: progressive muscle relaxation (PMR) standardized instructed PMR (20 minutes), 9 sessions | Device: Sham tDCS<br>* Sham transcranial direct current stimulation (tDCS), 9 sessions with 30 sec stimulation each (2 mA) to ensure blinding of participants<br>Behavioral: Progressive muscle relaxation (PMR)<br>* Standardized instructed PMR training, 9 sessions<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Working memory performance at post-assessment | Percent change of correct responses in the n-back task compared to the pre-training assessment. | 3 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Working memory performance at follow-up assessment | Percent change of correct responses in the n-back task compared to the pre-training assessment. | 4 weeks after training | 
| Working memory training performance (Letter Updating Task) at post-assessment | Performance in primary memory training task (Letter Updating Task) at post-assessment, operationalized by number of correctly recalled lists in the letter updating task. | 3 weeks | 
| Working memory training performance (Letter Updating Task) at follow-up assessment | Performance in primary memory training task (Letter Updating Task) at follow-up assessment, operationalized by number of correctly recalled lists in the letter updating task. | 4 weeks after training | 
| Quality of Life at post-assessment | PROMIS (Patient-Reported Outcome Measures and Health-Related Quality of Life) score for HRQoL (PROPr score) and scores of subscales (e.g. cognitive function). Every item is rated on scale from 1 to 5, the higher the score the worse the self-reported health evaluation. | 3 weeks | 
| Quality of Life at follow-up assessment | PROMIS (Patient-Reported Outcome Measures and Health-Related Quality of Life) score for HRQoL (PROPr score) and scores of subscales (e.g. cognitive function). Every item is rated on scale from 1 to 5, the higher the score the worse the self-reported health evaluation. | 4 weeks after training | 
| Visuo-spatial performance at post-assessment | Visuo-spatial performance at post-assessment operationalized by number of correctly recalled items in the VR task. | 3 weeks | 
| Visuo-spatial performance at follow-up assessment | Visuo-spatial performance at follow-up assessment operationalized by number of correctly recalled items in the VR task. | 4 weeks after training | 
| Post COVID-19 Function at post-assessment | Scores of Post COVID-19 Functional Scale (PCFS). PCFS scale grad from 0 (no functional limitations) to 4 (severe functional limitations). | 3 weeks | 
| Post COVID-19 Function at follow-up assessment | Scores of Post COVID-19 Functional Scale (PCFS). PCFS scale grad from 0 (no functional limitations) to 4 (severe functional limitations). | 4 weeks after training |