Exercise + Cognitive Training for Long COVID

Overseen By Jennifer K Fairchild, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: VA Office of Research and Development

Disqualifiers: Severe psychotic disorder, Stroke, Parkinson's, Alzheimer's, others

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

Compensation: Varies

Number of Visits: 3

50 Participants Needed

Trial Summary

What is the purpose of this trial?

This two-year study will evaluate the feasibility and safety of an exercise + cognitive training program to improve neurological symptoms of long-COVID. This is a two-phased trial: 1) an exercise phase and 2) a cognitive training phase. The exercise phase will be an aquatic based exercise program. A combination exercise + memory training programs designed for persons with cognitive impairment have significantly improved memory more than other single intervention groups (exercise only, cognitive training only) and given the success of combination training programs with healthy adults, it is important to adapt these programs for persons with neurological symptoms of long-COVID.

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's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment WATER+CT for Long COVID?

Research suggests that combining cognitive training with physical activity can improve cognitive function, as seen in studies with older adults and those with traumatic brain injury. This indicates that the WATER+CT treatment, which combines aquatic exercise with cognitive training, may help improve cognitive issues in Long COVID patients. ^{1 2 3 4 5}

Is aquatic exercise safe for humans?

Aquatic exercise programs have been shown to be safe and beneficial for improving physical fitness and health in both healthy adults and those with chronic diseases. Studies indicate that these programs can enhance strength, balance, and cardiorespiratory fitness without significant safety concerns. ^{6 7 8 9 10}

How does the Exercise + Cognitive Training treatment for Long COVID differ from other treatments?

This treatment is unique because it combines physical exercise with cognitive training, which has shown potential benefits for cognitive function in older adults and those with degenerative diseases. Unlike standard treatments that may focus solely on physical or cognitive aspects, this approach aims to enhance both physical and mental recovery, potentially offering a more comprehensive benefit for Long COVID patients. ^{1 2 4 5 11}

Research Team

Jennifer Kaci Fairchild, PhD

Principal Investigator

VA Palo Alto Health Care System, Palo Alto, CA

Eligibility Criteria

This trial is for veterans aged 18-89 with long COVID neurological symptoms like 'brain fog', who can undergo neuropsychological testing and water-based exercise. They must have had COVID-19 at least 6 months prior, with ongoing symptoms for over 8 weeks. Those with severe pre-existing conditions or current severe cardiac disease cannot participate.

Inclusion Criteria

You had COVID-19 more than 6 months ago, and it was confirmed by a doctor.

I have had 'brain fog' or trouble thinking clearly for at least 8 weeks since getting COVID-19.

I can see and hear well enough to take psychological tests.

Exclusion Criteria

I had a neurological or neurodegenerative condition, or a serious illness affecting my brain function before getting COVID-19.

I do not have severe heart problems or recent serious blood clots.

You cannot do an exercise stress test.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Exercise Training

Participants undergo a six-month long individualized water-based exercise program with thrice-weekly group sessions

6 months

3 visits per week (in-person)

Cognitive Training

Participants engage in classroom-based cognitive training focusing on pre-training and mnemonic training

2 months

Regular classroom sessions (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• WATER+CT

Trial Overview The study tests a two-phase program combining aquatic exercises and cognitive training to improve long-COVID neurological issues. Participants will first engage in water-based exercises followed by memory training, assessing the combined effect on recovery.

Participant Groups

Group I: WATER+CT Experimental Treatment 1 Intervention

This is 8-month long two phase intervention consisting of: 1) 6 months of aquatic exercise followed by 2) 2 months of cognitive training.

Group II: Usual Care Experimental Treatment 1 Intervention

This arm consists of psychoeducation regarding brain health and healthy lifestyles.

Who Is Running the Clinical Trial?

VA Office of Research and Development

Lead Sponsor

Trials

1,691

Recruited

3,759,000+

Findings from Research

In a study of 55 healthy older adults, cognitive physical training (CPT) showed significant long-term benefits in overall cognition and verbal long-term memory compared to CPT with counseling, suggesting that combining cognitive and physical activities is effective for maintaining cognitive health.

Predictors of success in CPT included initial low performance in verbal short-term memory and fluency, as well as baseline levels of insulin-like growth factor 1 (IGF-1) and brain-derived neurotrophic factor (BDNF), indicating that individual characteristics can influence the effectiveness of cognitive training interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of a Cognitive Training With and Without Additional Physical Activity in Healthy Older Adults: A Follow-Up 1 Year After a Randomized Controlled Trial. Kalbe, E., Roheger, M., Paluszak, K., et al.[2020]

Cognitive training exercises (CTE) were found to be feasible and potentially effective for enhancing cognitive function in Egyptian adults, particularly those with mild cognitive impairment (MCI), after a 12-week program involving various cognitive tasks.

Participants who completed the CTE showed significant improvements in several cognitive assessments, including memory and executive function, indicating that CTE can help slow cognitive deterioration in individuals with subjective memory impairment and MCI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pilot feasibility study of cognitive training exercises for Egyptian adults: Proof of concept. Tawfik, HM., Tsatali, M., Hassanin, HI.[2021]

Cognitive training (CT) has a small but statistically significant effect on overall cognition in patients with traumatic brain injury (TBI) more than 12 months post-injury, based on a meta-analysis of 14 studies involving 575 patients.

CT shows a moderate effect on overall functional outcomes and is particularly effective in improving executive function and verbal memory, suggesting it should be more widely integrated into TBI rehabilitation programs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cognitive Training for Post-Acute Traumatic Brain Injury: A Systematic Review and Meta-Analysis. Hallock, H., Collins, D., Lampit, A., et al.[2020]

A 6-month randomized controlled trial will assess the effects of aerobic training (AT), resistance training (RT), and their combination on cognitive function in 216 older adults (ages 65-85) with mild cognitive impairment (MCI).

The study aims to determine how different types of exercise can help prevent cognitive decline and potentially delay the onset of dementia, highlighting the importance of exercise as a therapeutic intervention for cognitive health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reshaping the path of mild cognitive impairment by refining exercise prescription: a study protocol of a randomized controlled trial to understand the "what," "for whom," and "how" of exercise to promote cognitive function. Barha, CK., Falck, RS., Best, JR., et al.[2022]

Cognitive training combined with physical activity (CPT) showed stronger long-term effects on attention in older adults compared to cognitive training alone (CT), particularly noticeable at a 1-year follow-up after 6.5 weeks of training.

Both CPT and CT improved cognitive functions such as cognitive state, verbal fluency, and memory, but the specific benefits of CPT may be influenced by ongoing physical activity after the training sessions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of cognitive training with additional physical activity compared to pure cognitive training in healthy older adults. Rahe, J., Petrelli, A., Kaesberg, S., et al.[2019]

A 16-week water-based aerobic training program significantly improved functional capacity and reduced blood pressure in older women, with improvements ranging from 3-11% in functional capacity and 4-10 mmHg in blood pressure.

Cognitive function did not show any significant changes across all groups, indicating that while physical training is beneficial for functional and hemodynamic responses, it may not impact cognitive abilities in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Water-Based Training Programs Improve Functional Capacity, Cognitive and Hemodynamic Outcomes? The ACTIVE Randomized Clinical Trial. Häfele, MS., Alberton, CL., Häfele, V., et al.[2023]

Deep Water Running (DWR) is as effective as land-based training for improving cardiorespiratory fitness, based on a systematic review of 11 studies involving 287 participants.

DWR may offer benefits for individuals who are weak, injured, or in pain, as the aquatic environment allows for high-intensity exercise with less strain on the body, although more research is needed to confirm these advantages.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of Deep Water Running on Improving Cardiorespiratory Fitness, Physical Function and Quality of Life: A Systematic Review. Kwok, MMY., So, BCL., Heywood, S., et al.[2022]

A study involving 102 elderly individuals showed that different aquatic exercise programs significantly improved body composition, functional fitness, and cognitive function over 28 weeks.

The combined exercise program (ComG) was particularly effective for enhancing body composition and cognitive function, while the intensity (IntG) and aerobic (AerG) programs were better for improving functional fitness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of Different Aquatic Exercise Programs on Body Composition, Functional Fitness and Cognitive Function of Non-Institutionalized Elderly Adults: A Randomized Controlled Trial. Farinha, C., Teixeira, AM., Serrano, J., et al.[2021]

A study involving 67 older adults with mild cognitive impairment (MCI) showed that both water-based and land-based exercise combined with cognitive training significantly improved learning and memory outcomes over 6 months.

However, improvements in executive functioning, processing speed, language, and visuospatial abilities were only observed in the water-based exercise group, suggesting that aquatic activities may offer additional cognitive benefits for older adults with MCI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cognitive Improvement Following Physical Exercise and Cognitive Training Intervention for Older Adults With MCI. Campbell, EB., Delgadillo, M., Lazzeroni, LC., et al.[2023]

A systematic review of 62 studies found that water-based training (WT) significantly improves strength, balance, and cardiorespiratory fitness in healthy adults when performed for at least 12 weeks, 2-3 times a week.

For adults with chronic diseases, WT led to notable health benefits, including improved quality of life and physical fitness in conditions like fibromyalgia, diabetes, and Parkinson's disease, particularly after 8-16 weeks of training.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Benefits of aquatic exercise in adults with and without chronic disease-A systematic review with meta-analysis. Faíl, LB., Marinho, DA., Marques, EA., et al.[2022]

The SmartTapestry device, tested on 53 participants (29 healthy and 24 with mild cognitive impairment), effectively combines physical activity with cognitive training, showing a strong correlation with traditional cognitive tasks.

This innovative approach suggests that cognitive-physical training tools can enhance cognitive function while being used at home, potentially improving treatment efficacy for cognitive impairments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Can physical and cognitive training based on episodic memory be combined in a new protocol for daily training? Maselli, M., Fiorini, L., Cecchi, F., et al.[2020]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Effects of a Cognitive Training With and Without Additional Physical Activity in Healthy Older Adults: A Follow-Up 1 Year After a Randomized Controlled Trial. [2020]

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

Pilot feasibility study of cognitive training exercises for Egyptian adults: Proof of concept. [2021]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Cognitive Training for Post-Acute Traumatic Brain Injury: A Systematic Review and Meta-Analysis. [2020]

4. England pubmed.ncbi.nlm.nih.gov

Reshaping the path of mild cognitive impairment by refining exercise prescription: a study protocol of a randomized controlled trial to understand the "what," "for whom," and "how" of exercise to promote cognitive function. [2022]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Effects of cognitive training with additional physical activity compared to pure cognitive training in healthy older adults. [2019]

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

Water-Based Training Programs Improve Functional Capacity, Cognitive and Hemodynamic Outcomes? The ACTIVE Randomized Clinical Trial. [2023]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Effectiveness of Deep Water Running on Improving Cardiorespiratory Fitness, Physical Function and Quality of Life: A Systematic Review. [2022]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Impact of Different Aquatic Exercise Programs on Body Composition, Functional Fitness and Cognitive Function of Non-Institutionalized Elderly Adults: A Randomized Controlled Trial. [2021]

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

Cognitive Improvement Following Physical Exercise and Cognitive Training Intervention for Older Adults With MCI. [2023]

10. Denmark pubmed.ncbi.nlm.nih.gov

Benefits of aquatic exercise in adults with and without chronic disease-A systematic review with meta-analysis. [2022]

11. Germany pubmed.ncbi.nlm.nih.gov

Can physical and cognitive training based on episodic memory be combined in a new protocol for daily training? [2020]