Cognitive Rehabilitation for Long COVID Brain Fog

Overseen By Madeline Rathz, BS

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Alabama at Birmingham

Disqualifiers: Developmental disability, Psychiatric disorder, Substance abuse, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 17

Duration: 2-4 weeks

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to assist people with long COVID who experience persistent brain fog and mild to moderate cognitive issues. Researchers will compare two types of cognitive rehabilitation: Processing Speed Training, which focuses on improving processing speed and work-related tasks, and Reaction Time Training, which enhances reaction time and healthy lifestyle habits. Both approaches include non-invasive vagus nerve stimulation, a procedure that might improve cognitive function. People who have faced brain fog and cognitive challenges for at least three months after COVID and struggle with daily activities might be suitable candidates. Participants can also receive vocational rehabilitation if they need help returning to work. As an unphased trial, this study offers an opportunity to explore innovative cognitive rehabilitation methods that could enhance daily functioning.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It is best to discuss this with the trial coordinators or your healthcare provider.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that both treatments under study, Constraint-Induced Cognitive Therapy (CICT) and Brain Fitness Training (BFT), are considered safe so far. Earlier studies have used CICT with stroke survivors, and it is well-tolerated by individuals with mild-to-moderate cognitive issues. Although specific side effects weren't detailed, the absence of reported problems suggests general safety.

For Brain Fitness Training, the research focuses on exercises that improve habits and thinking skills. Studies have shown that similar brain-training exercises for long COVID symptoms have been used without major safety concerns, indicating typical safety.

Both treatments in this study include trans-auricular vagus nerve stimulation (taVNS). Research indicates that taVNS is generally safe and well-tolerated, with mostly mild and short-lived side effects. This non-invasive method has been used for various conditions, enhancing its safety record.

Overall, the treatments have demonstrated a promising safety record. Participants considering joining the trial are likely to find the interventions well-tolerated based on available evidence. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about these cognitive rehabilitation methods for Long COVID brain fog because they combine innovative techniques like processing speed and reaction time training with non-invasive vagus nerve stimulation. Unlike traditional treatments that might focus solely on therapy or medication, these approaches integrate cognitive exercises with lifestyle changes, such as vocational rehabilitation and healthy living practices. This comprehensive strategy aims to enhance everyday cognitive functions and promote lasting improvements, offering a fresh and potentially more holistic solution for those struggling with persistent cognitive issues post-COVID.

What evidence suggests that this trial's treatments could be effective for long COVID brain fog?

Research has shown that Constraint-Induced Cognitive Therapy (CICT), one of the treatments tested in this trial, can improve symptoms of long COVID, such as brain fog. Studies have found that people who tried CICT experienced a significant reduction in brain fog and tiredness. In another study, participants noticed significant improvements in their thinking skills and ability to work.

Brain Fitness Training (BFT), another treatment option in this trial, also shows promise. A review found that many participants experienced less brain fog and fatigue, suggesting that BFT could help manage these long COVID symptoms.

Additionally, trans-auricular Vagus Nerve Stimulation (taVNS), included in the various treatment arms of this trial, has improved long COVID symptoms, including cognitive issues. Studies indicate that taVNS can be a safe and effective way to ease symptoms like brain fog. ^{1 2 6 7 8}

Who Is on the Research Team?

Gitendra Uswatte, PhD

Principal Investigator

Professor of Psychology, University of Alabama at Birmingham

Are You a Good Fit for This Trial?

Adults with long COVID experiencing mild to moderate cognitive issues, such as brain fog and trouble with daily activities. They must be over 3 months post-COVID, able to travel to the lab, mentally and physically fit enough for participation, have good vision and hearing, follow instructions well, and speak English. Excluded are those with a history of stroke before COVID-19 or current substance abuse.

Inclusion Criteria

I struggle with daily activities due to my condition.

I can follow directions and remember information.

I had COVID-19 over 3 months ago.

Exclusion Criteria

Current substance abuse disorder

I had a stroke before getting COVID.

I have previously completed a cognitive speed training program like DoubleDecision.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

1 visit (in-person)

Treatment

Participants undergo 30 hours of training over 2 to 4 weeks, including web-based games, in-lab training, and vagus nerve stimulation

2-4 weeks

10 visits (in-person)

Follow-up

Participants receive four follow-up phone calls to promote integration of skills gained during training into everyday life

4 weeks

4 calls (virtual)

Long-term Follow-up

Participants are monitored for cognitive processing speed and performance in everyday activities at 6 and 12 months post-treatment

12 months

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Processing Speed Training
• Reaction Time Training
• Trans-auricular Vagus Nerve Stimulation: High Intensity
• Trans-auricular Vagus Nerve Stimulation: Low Intensity

Trial Overview

The trial compares two cognitive rehabilitation methods: Constraint-Induced Cognitive Therapy (CICT) focuses on processing speed training and practical tasks including work-related ones; Brain Fitness Training (BFT) emphasizes reaction time training along with lifestyle habits like relaxation. Both use non-invasive vagus nerve stimulation (taVNS) and may include vocational rehab for eligible participants.

How Is the Trial Designed?

Group I: CICT + VR Experimental Treatment 7 Interventions

Constraint-Induced Cognitive Therapy plus Vocational Rehabilitation uses in-lab training on everyday activities with important cognitive components and procedures designed to transfer improvements from the treatment setting to every day life. This will be combined with computer-based processing speed training and non-invasive vagus nerve stimulation. This group will also receive vocational rehabilitation from the Alabama Department of Rehabilitation Services, such as career counseling and building important career skills.

Group II: CICT Experimental Treatment 5 Interventions

Constraint-Induced Cognitive Therapy uses in-lab training on everyday activities with important cognitive components and procedures designed to transfer improvements from the treatment setting to every day life. This will be combined with computer-based processing speed training and non-invasive vagus nerve stimulation.

Group III: BFT Active Control 5 Interventions

Brain Fitness Training involves in-lab training on relaxation, healthy nutrition, and healthy sleep with procedures designed to promote integration of these lifestyles into everyday life. This will be combined with computer-based reaction time training and non-invasive vagus nerve stimulation.

Group IV: BFT + VR Active Control 6 Interventions

Brain Fitness Training plus Vocational Rehabilitation involves in-lab training on relaxation, healthy nutrition, and healthy sleep with procedures designed to promote integration of these lifestyles into everyday life. This will be combined with computer-based reaction time training and non-invasive vagus nerve stimulation. This group will also receive vocational rehabilitation from the Alabama Department of Rehabilitation Services, such as career counseling and building important career skills.

Processing Speed Training is already approved in United States, Canada for the following indications:

Approved in United States as Speed of Processing Training for:

• Cognitive impairment in older adults
• Long COVID brain fog

Approved in Canada as Speed of Processing Training for:

• Cognitive impairment in older adults
• Long COVID brain fog

Who Is Running the Clinical Trial?

University of Alabama at Birmingham

Lead Sponsor

Trials

1,677

Recruited

2,458,000+

Posit Science

Collaborator

Trials

2

Recruited

120+

National Institute on Disability, Independent Living, and Rehabilitation Research

Collaborator

Trials

83

Recruited

10,500+

Published Research Related to This Trial

In a randomized trial involving older adults (ages 57-71), cognitive training over 12 weeks significantly improved processing speed compared to wait-listed and exercise control groups, indicating its efficacy in enhancing cognitive function.

The cognitive training led to a notable change in neural activity, where faster reaction times were linked to reduced activation in the left prefrontal cortex, suggesting a more efficient neural processing mechanism in the CT group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Higher-order cognitive training effects on processing speed-related neural activity: a randomized trial. Motes, MA., Yezhuvath, US., Aslan, S., et al.[2022]

A study of Veterans with traumatic brain injury (TBI) showed that both those with cognitive difficulties and those with normal cognition improved in executive functioning and memory after participating in a group-format EF training, with significant improvements observed at least six months post-training.

Veterans with cognitive difficulties experienced greater improvements in learning and memory compared to those with normal cognition, suggesting that cognitive rehabilitation can be particularly beneficial for individuals with more severe cognitive impairments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Effect of Cognitive Rehabilitation Regardless of Prerehabilitation Cognitive Status for Veterans with TBI. Kornblith, E., Posecion, L., Abrams, G., et al.[2021]

A pilot study involving 73 adults with cognitive dysfunction post-COVID-19 showed that an 8-week personalized computerized cognitive training (CCT) significantly improved cognitive function across multiple domains, including attention, memory, and reasoning.

Participants reported higher cognitive scores after the training compared to their baseline assessments, indicating that self-administered CCT could be an effective intervention for alleviating cognitive issues in individuals suffering from post-acute sequelae of COVID-19.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Personalized Computerized Training for Cognitive Dysfunction after COVID-19: A Before-and-After Feasibility Pilot Study. Duñabeitia, JA., Mera, F., Baro, Ó., et al.[2023]

In a study involving 681 participants aged 50 and older, cognitive speed of processing training (SOPT) did not significantly enhance overall cognitive abilities compared to an attention-control group that engaged in crossword puzzles.

Despite the training showing a statistically significant time effect on cognitive processing, there was no notable difference in improvement across different treatment groups or age bands after 10-14 hours of SOPT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of cognitive speed of processing training on a composite neuropsychological outcome: results at one-year from the IHAMS randomized controlled trial. Wolinsky, FD., Vander Weg, MW., Howren, MB., et al.[2022]

A pilot study involving six patients with mild traumatic brain injury (TBI) or non-traumatic acquired brain injury (ABI) showed significant cognitive improvements after 60 hours of a cognitive training program called Brain Booster, with notable increases in long-term memory, processing speed, reasoning, and a mean IQ score increase of 20 points.

MRI results indicated significant changes in brain connectivity, particularly in the cerebellum, and correlations between cognitive improvements and white matter integrity, suggesting that cognitive training can enhance both cognitive function and underlying neural structures in individuals with mild brain injuries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neuroimaging and Neuropsychological Outcomes Following Clinician-Delivered Cognitive Training for Six Patients With Mild Brain Injury: A Multiple Case Study. Moore, AL., Carpenter, DM., James, RL., et al.[2020]

This study will evaluate the effectiveness of Goal Management Training (GMT) in improving attention and executive functions in 240 adults who have persistent cognitive deficits after COVID-19, with results expected at six months post-treatment.

Participants will be randomly assigned to either the GMT group or a waitlist control, allowing for a comparison of cognitive improvements, which could lead to evidence-based treatment options for common post-COVID-19 cognitive issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cognitive rehabilitation in post-COVID-19 condition: A study protocol for a randomized controlled trial. Hagen, BI., Lerdal, A., Søraas, A., et al.[2023]

COVID-19 survivors are experiencing cognitive problems, often referred to as 'brain fog', which can significantly impact their daily activities and ability to return to work.

There is a need for further research into the nature and prevalence of these cognitive issues, as well as the potential application of brain injury recovery treatments to help improve cognitive function in these individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A proposal to apply brain injury recovery treatments for cognitive impairment in COVID-19 survivors. Nouraeinejad, A.[2022]

This study will investigate the effects of cognitive training, with and without transcranial direct current stimulation (tDCS), on cognitive performance and quality of life in patients experiencing cognitive impairments after COVID-19, involving a 3-week intervention period.

The primary outcome will focus on improvements in working memory, assessed through an n-back task, with secondary outcomes including overall cognitive performance and health-related quality of life measured at post-intervention and one month later.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Thams, F., Antonenko, D., Fleischmann, R., et al.[2022]

A 4-week interactive cognitive-motor training (CMT) program significantly improved cognitive health components, including depression, anxiety, and overall mental health scores, in 42 elderly men who had recovered from COVID-19.

Participants showed lasting improvements in cognitive functions such as attention, recall, and language skills, indicating that CMT is an effective intervention for enhancing cognitive health in older adults post-COVID-19.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effectiveness of cognitive-motor training on reconstructing cognitive health components in older male adults, recovered from the COVID-19. Amini, A., Vaezmousavi, M., Shirvani, H.[2022]

Computerized cognitive training (CCT) significantly improved overall cognitive function, attention, and memory in older adults with traumatic brain injury compared to usual care over a 6-month period.

Tai chi (TC) also enhanced cognitive scores and showed lasting benefits, particularly in conceptualization and initiation/preservation, with effects observed up to 12 months, while also improving physical strength and mobility.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Computerized Cognitive Training and Tai Chi on Cognitive Performance in Older Adults With Traumatic Brain Injury. Hwang, HF., Chen, CY., Wei, L., et al.[2021]

In a randomized controlled trial with 60 participants with multiple sclerosis, Speed of Processing Training (SOPT) led to significant improvements in everyday functional outcomes, specifically in the Timed Instrumental Activities of Daily Living (TIADL) scores compared to an active control group.

While SOPT improved cognitive performance in some participants, it did not result in overall changes in quality of life or self-reported functional status, indicating that while cognitive training can enhance certain skills, it may not fully translate to broader functional improvements.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Efficacy of the Speed of Processing Training Program in Improving Functional Outcome: From Restoration to Generalization. Goverover, Y., Costa, S., DeLuca, J., et al.[2023]

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