Exercise for Stroke Recovery

(AMPLIFI Trial)

Overseen By Sarah Bruton, BS

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Alabama at Birmingham

Must not be taking: CNS medications

Disqualifiers: Epilepsy, Substance abuse, Cardiovascular, others

Compensation: Varies

Number of Visits: 8

Duration: 2-3 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to understand how different types of exercise affect brain health, movement, and memory in older adults and stroke survivors. Participants will engage in either high-intensity aerobic exercise (cycling to increase lactate levels, a substance produced during exercise that might benefit the brain), low-intensity cycling, or health education sessions. Researchers will assess the impact of exercise on brain function using simple motor learning tasks and a safe brain stimulation test. Suitable candidates are right-handed, English-speaking individuals who can safely perform moderate exercise and have no metal in their skull or history of seizures. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research on exercise and brain health.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, younger adults cannot be on medications that affect the central nervous system.

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

Research has shown that aerobic exercise, especially when it raises lactate levels, is generally safe for people recovering from a stroke. Studies have found that this type of exercise can improve brain function and movement. For example, lactate might aid in better brain control.

Aerobic exercise also reduces heart-related risks and enhances the quality of life for stroke survivors. It is often recommended during stroke recovery to boost fitness and recovery. This exercise can be tailored to fit a person's fitness level, making it safer and more effective over time.

Overall, aerobic exercise at different intensities has proven to be a safe option for stroke recovery, benefiting both brain and body health. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using aerobic exercise for stroke recovery because it offers a unique approach by directly engaging neuromodulatory pathways associated with brain plasticity. Unlike traditional rehabilitation methods that focus primarily on physical therapy and medication, aerobic exercise at the lactate threshold induces metabolic stress, which may enhance the brain's ability to relearn and adapt. This technique could potentially accelerate recovery and improve motor learning outcomes more effectively than low-intensity exercises or passive educational sessions.

What evidence suggests that this trial's exercise interventions could be effective for stroke recovery?

This trial will compare different approaches to aerobic exercise for stroke recovery. Research has shown that aerobic exercise can significantly aid stroke recovery. Studies have found that exercise lowers blood pressure and boosts fitness levels in stroke patients. Starting aerobic exercise within six months after a stroke may improve movement and balance. Early evidence suggests that reaching a certain level of effort during exercise might enhance brain function by improving self-control. These benefits for movement and brain health make exercise a promising option for stroke recovery. Participants in this trial will join one of three groups: Aerobic Exercise at Lactate Threshold, Low-Intensity Aerobic Exercise, or an Education Control group. ^{1 6 7 8 9}

Are You a Good Fit for This Trial?

The AMPLIFI study is for older adults and stroke survivors interested in how exercise affects brain health. Participants should be able to perform physical tasks and attend multiple sessions. Those with certain medical conditions or taking specific medications that affect brain plasticity may not qualify.

Inclusion Criteria

For All Participants: Able to provide informed consent

For All Participants: Right-handed (for TMS consistency)

For All Participants: Clearance for moderate-intensity aerobic exercise

Exclusion Criteria

Contraindications to TMS or exercise testing (e.g., implanted neurostimulators, severe hypertension)

Pregnancy

Participation in another interventional trial within the past 30 days

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-3 weeks

1 visit (in-person)

Baseline Assessment

Participants undergo baseline assessments including VO2 max testing, cognitive and motor testing, and blood draws

1 week

1 visit (in-person)

Treatment

Participants complete five sessions of either aerobic exercise or health education, with TMS and motor learning tasks conducted pre- and post-intervention

2-3 weeks

5 visits (in-person)

Follow-up

Participants are monitored for changes in cortical inhibition, motor learning, and executive function

1 week

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Aerobic Exercise

Trial Overview This trial tests the effects of different intensities of cycling exercises versus health education on brain function, movement, and memory. It involves motor learning tasks and non-invasive brain stimulation testing to measure the impact of exercise on neuroplasticity.

How Is the Trial Designed?

Group I: Aerobic Exercise at Lactate Threshold Experimental Treatment 1 Intervention

Participants complete a 20-minute aerobic cycling session at individually prescribed intensity to achieve lactate threshold, based on VO2 max and blood lactate data. This condition is designed to induce metabolic stress and engage neuromodulatory pathways related to cortical plasticity. Participants complete TMS and motor learning tasks before and after the intervention.

Group II: Low-Intensity Aerobic Exercise Active Control 1 Intervention

Participants complete a 20-minute cycling session at a light workload, below lactate threshold. This condition controls for movement and engagement without significant metabolic challenge. TMS and motor learning outcomes are assessed pre- and post-intervention.

Group III: Education Control Placebo Group 1 Intervention

Participants engage in a 20-minute health education session instead of exercise. This arm serves as a non-exercise control to isolate the effects of physical exertion on neuroplasticity. All outcome measures are collected similarly to the exercise groups.

Who Is Running the Clinical Trial?

University of Alabama at Birmingham

Lead Sponsor

Trials

1,677

Recruited

2,458,000+

Published Research Related to This Trial

In a study of 195 stroke patients undergoing submaximal exercise testing, only 2.1% showed significant ECG abnormalities, suggesting that most patients can safely engage in aerobic exercise early in rehabilitation without constant ECG monitoring.

The study indicates that using symptom monitoring and conservative heart rate limits can help physical therapists prescribe safe exercise intensities for stroke patients, even when ECG testing is not available.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Determining Safe Participation in Aerobic Exercise Early After Stroke Through a Graded Submaximal Exercise Test. Inness, EL., Aqui, A., Foster, E., et al.[2021]

Aerobic exercise is crucial for improving cardiovascular health and overall quality of life in stroke survivors, yet it is often underutilized in rehabilitation plans.

The review emphasizes the FITT principle (frequency, intensity, time, type) for exercise prescription and highlights the potential benefits of high-intensity interval training in reaching higher target heart rates for stroke patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Does aerobic exercise and the FITT principle fit into stroke recovery? Billinger, SA., Boyne, P., Coughenour, E., et al.[2018]

A scoping review of 13 studies involving 452 participants found that submaximal aerobic exercise testing protocols for individuals post-stroke can be safely implemented without serious adverse events, addressing concerns about cardiovascular risks.

The most common comorbidities among participants included hypertension (41%), diabetes (31%), and dyslipidemia (27%), indicating that these factors should be considered when designing exercise protocols for stroke rehabilitation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse Events During Submaximal Aerobic Exercise Testing in People With Subacute Stroke: A Scoping Review. Legasto-Mulvale, JM., Inness, EL., Thompson, AN., et al.[2023]

In a study of 200 patients with moderate to severe subacute stroke, those who underwent aerobic training experienced a higher rate of serious adverse events compared to those in the relaxation control group, with an incident rate ratio of 1.70.

The occurrence of serious adverse events in the aerobic training group was significantly influenced by pre-existing conditions such as diabetes mellitus and atrial fibrillation, indicating that these factors may increase risk and warrant further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Physical Fitness Training in Patients with Subacute Stroke (PHYS-STROKE): Safety analyses of a randomized clinical trial. Rackoll, T., Nave, AH., Ebinger, M., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11973393/

Current exercise-based rehabilitation impacts on poststroke ... Overall, current exercise-based rehabilitation programs significantly improve blood pressure and exercise capacity in patients with stroke at discharge.

2. ahajournals.org ahajournals.org/doi/10.1161/JAHA.121.022588

Associations Between Time After Stroke and Exercise ... There may be a clinically meaningful benefit to mobility outcomes when exercise is initiated within 3 months and up to 6 months after stroke.

3. scirp.org scirp.org/journal/paperinformation?paperid=137506

Aerobic vs. Anaerobic Training in Post-Stroke Rehabilitation Both TAE and TAN contribute to post-stroke recovery, with TAN excelling in walking and balance improvements, and TAE showing advantages in functional mobility ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10776819/

Aerobic exercise improves cortical inhibitory function after stroke Our findings show preliminary evidence that lactate may play a role in exercise-induced improvements in inhibitory control after stroke.

5. mdpi.com mdpi.com/2077-0383/14/10/3327

Efficacy of Physical Therapy Rehabilitation in the ... The ideal time to commence aerobic training rehabilitation was found to be six months post-stroke.

6. ahajournals.org ahajournals.org/doi/10.1161/strokeaha.117.017962

Effects of High- Versus Moderate-Intensity Training on ... This study was designed to compare the effects of high-intensity interval training (HIT) and moderate-intensity aerobic training (MOD) on functional recovery ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4560458/

Does Aerobic Exercise and the FITT Principle Fit into ... Aerobic exercise has the potential to reduce cardiovascular risk factors and improve functional capacity and quality of life in people after stroke.

8. frontiersin.org frontiersin.org/journals/neurology/articles/10.3389/fneur.2019.01187/full

Aerobic Training and Mobilization Early Post-stroke Aerobic exercise can ideally increase in intensity as a function of elapsed time post-stroke and should be guided based on cardiopulmonary fitness measures ...

9. trialsjournal.biomedcentral.com trialsjournal.biomedcentral.com/articles/10.1186/s13063-021-05419-x

Moderate-intensity exercise versus high-intensity interval ... Current exercise recommendations and stroke rehabilitation guidelines recommend moderate-intensity aerobic training post-stroke. Locomotor high- ...