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

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

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.

Study Overview

• Status: Recruiting
• Conditions: COVID-19; Post-COVID-19
• Intervention / Treatment: Device: Anodal tDCS; Behavioral: Intensive cognitive training; Device: Sham tDCS; Behavioral: Progressive muscle relaxation (PMR)

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Agnes Flöel, Prof.; Phone Number: 0049 3834 86 6815; Email: agnes.floeel@med.uni-greifswald.de

Study Locations

• Germany
  • Greifswald, Germany
    • Recruiting
    • University Medicine Greifswald
    • Contact: Agnes Flöel, Prof.; Phone Number: 0049 3834 86 6815; Email: agnes.floeel@med.uni-greifswald.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 58 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. History of COVID-19 condition at least 4-6 weeks prior to study inclusion
2. Self-reported concerns regarding cognitive functioning.
3. Age: 18-60 years.

Exclusion Criteria:

1. Acute COVID-19 illness.
2. History of dementia before COVID-19.
3. Other neurodegenerative neurological disorders; epilepsy or history of seizures.
4. Severe and untreated medical conditions that preclude participation in the training, as determined by responsible physician.
5. History of severe alcoholism or use of drugs.
6. Severe psychiatric disorders such as severe depression (if not in remission) or psychosis.
7. Contraindication to tDCS application (Antal et al. 2017).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Anodal tDCS + cognitive training; 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; Anodal transcranial direct current stimulation (tDCS), 9 sessions with 20 minutes stimulation each (2 mA); Behavioral: Intensive cognitive training; Intensive cognitive training of a letter memory updating task, 9 sessions
Placebo Comparator: Sham tDCS + cognitive training; 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	Behavioral: Intensive cognitive training; Intensive cognitive training of a letter memory updating task, 9 sessions; Device: Sham tDCS; Sham transcranial direct current stimulation (tDCS), 9 sessions with 30 sec stimulation each (2 mA) to ensure blinding of participants
Active Comparator: Sham tDCS + Progressive Muscle Relaxation training; 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; Sham transcranial direct current stimulation (tDCS), 9 sessions with 30 sec stimulation each (2 mA) to ensure blinding of participants; Behavioral: Progressive muscle relaxation (PMR); Standardized instructed PMR training, 9 sessions

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University Medicine Greifswald
• Investigators: Study Director: Agnes Flöel, Prof., University Medicine Greifswald

Publications and helpful links

General Publications

• Thams F, Antonenko D, Fleischmann R, Meinzer M, Grittner U, Schmidt S, Brakemeier EL, Steinmetz A, Floel A. Neuromodulation through brain stimulation-assisted cognitive training in patients with post-COVID-19 cognitive impairment (Neuromod-COV): study protocol for a PROBE phase IIb trial. BMJ Open. 2022 Apr 11;12(4):e055038. doi: 10.1136/bmjopen-2021-055038.

Study record dates

Study Major Dates

• Study Start (Actual): January 5, 2022
• Primary Completion (Estimated): July 1, 2024
• Study Completion (Estimated): September 1, 2024

Study Registration Dates

• First Submitted: June 28, 2021
• First Submitted That Met QC Criteria: June 28, 2021
• First Posted (Actual): June 29, 2021

Study Record Updates

• Last Update Posted (Estimated): June 2, 2023
• Last Update Submitted That Met QC Criteria: June 1, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; Neurocognitive Disorders; Cognition Disorders; COVID-19; Cognitive Dysfunction
• Other Study ID Numbers: Neuromod-COV

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Anonymized data will be made available to the scientific community upon request.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No