Brain-Training Exercises for Long COVID

Overseen By Jennifer Brindisi, M.A.

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: UConn Health

Must not be taking: Psychiatric medications

Disqualifiers: Neurological disorder, MCI, psychiatric illness, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 6 weeks

40 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that if you are on psychiatric medications, you must be on a stable dose for at least 1 month before starting the study and have no plans to change the dose during the study.

What data supports the effectiveness of the treatment NeuroFlex for Long COVID?

Research on brain-training exercises, similar to NeuroFlex, shows they can improve cognitive and functional symptoms in people with traumatic brain injuries and seniors, suggesting potential benefits for Long COVID. Additionally, noninvasive brain stimulation techniques have shown early success in improving symptoms like brain fog and mood in Long COVID patients. ^{1 2 3 4 5}

Is the brain-training exercise NeuroFlex safe for humans?

The research does not provide specific safety data for NeuroFlex or similar brain-training exercises, but related interventions like progressive muscle relaxation and cognitive training have been studied for mental health and cognitive benefits in COVID-19 patients without reported safety concerns. ^{6 7 8 9 10}

How does the treatment NeuroFlex for Long COVID differ from other treatments?

NeuroFlex is unique because it involves brain-training exercises that aim to induce neuroplastic changes (the brain's ability to reorganize itself) to improve cognitive function, unlike other treatments that may focus on physical symptoms or use medication. ^{3 11 12 13 14}

What is the purpose of this trial?

This trial is testing if computerized brain-training exercises can help older adults with Long COVID. The goal is to see if these exercises can improve thinking, mood, and daily activities. The study will check if the exercises are easy to use and if they actually help.

Research Team

Cutter Lindbergh, Ph.D.

Principal Investigator

UConn Health

Eligibility Criteria

This trial is for older adults (55+) who've had COVID-19 and are experiencing ongoing cognitive symptoms that started after their illness. They should be fluent in English, have a certain level of cognitive function (TICS ≥ 27), and not planning to change any psychiatric medication doses during the study. People with neurological disorders, prior cognitive impairments unrelated to COVID-19, significant psychiatric conditions, recent substance use disorders, or major sensory/motor issues can't participate.

Inclusion Criteria

I am 55 years old or older.

I have ongoing thinking or memory problems after COVID-19 that other conditions don't explain.

You had COVID-19 in the past, confirmed by a positive laboratory test or a rapid test.

Exclusion Criteria

History of significant psychiatric illness per DSM-5 criteria that may interfere with study participation or confound results (e.g., schizophrenia or other psychotic disorder, bipolar and related disorders, major depressive disorder with psychotic features, personality disorder)

You have had a problem with alcohol or drugs in the past 2 years.

I do not have major sensory or motor issues that would stop me from participating in the study.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo computerized brain-training exercises to treat Long COVID symptoms

6 weeks

Initial visit (in-person), weekly virtual check-ins

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• NeuroFlex

Trial Overview The trial is testing 'NeuroFlex', which involves computerized brain-training exercises designed as games. The goal is to see if these exercises can help improve thinking, mood, and daily functioning in older adults suffering from Long COVID's lingering effects on cognition.

Participant Groups

Group I: Computerized Cognitive Remediation Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

UConn Health

Lead Sponsor

Trials

218

Recruited

59,100+

National Institute on Aging (NIA)

Collaborator

Trials

1,841

Recruited

28,150,000+

Findings from Research

The Brain Fitness Center (BFC) at Walter Reed National Military Medical Center has provided brain-training programs to over 250 military Service Members, showing promising results in reducing cognitive and functional symptoms after traumatic brain injury, as indicated by significant improvements in the Mayo-Portland Adaptability Inventory and Neurobehavioral Symptom Inventory scores.

Preliminary data from the first 29 participants suggest that while there was a notable reduction in symptom severity, there were no significant changes in overall life satisfaction, highlighting the need for further research to fully understand the efficacy of computer-based cognitive rehabilitation programs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes from a pilot study using computer-based rehabilitative tools in a military population. Sullivan, KW., Quinn, JE., Pramuka, M., et al.[2018]

A 36-year-old male with long-COVID symptoms showed significant improvement in mood, sense of smell, and cognitive function after 10 sessions of personalized transcranial magnetic stimulation (EMBP®), indicating potential efficacy of this treatment for long-COVID.

Post-treatment assessments revealed a notable increase in forced expiratory volume and cognitive test scores, along with EEG changes suggesting enhanced brain activity, highlighting the need for further research into noninvasive brain stimulation techniques for long-COVID symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Case Report of Improvement in Long-COVID Symptoms in an Air Force Medic Treated With Transcranial Magnetic Stimulation Using Electro-Magnetic Brain Pulse Technique. Zhang, JX., Zhang, JJ.[2023]

A study involving 24 Veterans with chronic traumatic brain injury (TBI) showed that long-term executive function training (GOALS) led to significant improvements in attention, functional task performance, and emotional regulation, assessed over 6+ months after training.

Participants reported a notable increase in their likelihood of engaging in competitive employment or volunteering, rising from 26% at baseline to 61% at follow-up, indicating the training's positive impact on daily functioning and quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term effects of executive function training among veterans with chronic TBI. Novakovic-Agopian, T., Kornblith, E., Abrams, G., et al.[2021]

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 55-year-old man with long COVID symptoms showed significant improvements in cognitive functions and physical capacity after 60 sessions of hyperbaric oxygen therapy, suggesting its potential as a treatment option.

Improvements included enhanced memory, attention, and exercise capacity, which correlated with increased cerebral blood flow, indicating that hyperbaric oxygen therapy may help address the underlying mechanisms of long COVID.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperbaric oxygen treatment for long coronavirus disease-19: a case report. Bhaiyat, AM., Sasson, E., Wang, Z., et al.[2022]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Outcomes from a pilot study using computer-based rehabilitative tools in a military population. [2018]

2. England pubmed.ncbi.nlm.nih.gov

Case Report of Improvement in Long-COVID Symptoms in an Air Force Medic Treated With Transcranial Magnetic Stimulation Using Electro-Magnetic Brain Pulse Technique. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Neural mechanisms of brain plasticity with complex cognitive training in healthy seniors. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Neural correlates of reduced depressive symptoms following cognitive training for chronic traumatic brain injury. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Long-term effects of executive function training among veterans with chronic TBI. [2021]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Positive Impacts of a Four-Week Neuro-Meditation Program on Cognitive Function in Post-Acute Sequelae of COVID-19 Patients: A Randomized Controlled Trial. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

Progressive muscle relaxation exercises in patients with COVID-19: Systematic review and meta-analysis. [2023]

8. England 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. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Role of Microglia, Decreased Neurogenesis and Oligodendrocyte Depletion in Long COVID-Mediated Brain Impairments. [2023]

10. England pubmed.ncbi.nlm.nih.gov

Hyperbaric oxygen treatment for long coronavirus disease-19: a case report. [2022]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Microscopic Fractional Anisotropy Detects Cognitive Training-Induced Microstructural Brain Changes. [2022]

12. United States pubmed.ncbi.nlm.nih.gov

Training induces changes in white-matter architecture. [2023]

13. England pubmed.ncbi.nlm.nih.gov

The Impact of Cognitive Training on Cerebral White Matter in Community-Dwelling Elderly: One-Year Prospective Longitudinal Diffusion Tensor Imaging Study. [2018]

14. United States pubmed.ncbi.nlm.nih.gov

Memory training impacts short-term changes in aging white matter: a longitudinal diffusion tensor imaging study. [2021]