Exercise Intervention for Carotid Stenosis and Mobility Impairment

(ACCOF-Ex Trial)

Overseen By Sarasijhaa K Desikan, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: VA Office of Research and Development

Must not be taking: Sedatives

Disqualifiers: Stroke, Severe stenosis, Dementia, others

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

Compensation: Varies

Number of Visits: 36

Duration: 12 weeks

50 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, if you are taking sedative medications, you may be excluded from participating.

What data supports the effectiveness of the treatment Exercise Intervention, Physical Activity Intervention, Exercise Program, Aerobic and Resistance Training for Carotid Stenosis and Mobility Impairment?

Research shows that exercise programs, including aerobic and resistance training, can improve exercise capacity and quality of life in patients with heart and vascular conditions. These benefits suggest that similar exercise interventions might help people with carotid stenosis and mobility issues by enhancing their physical function and overall well-being. ^{1 2 3 4 5}

Is exercise intervention safe for people with cardiovascular conditions?

Exercise interventions, including high-intensity interval training and resistance exercises, have been shown to be generally safe for people with cardiovascular conditions when done under supervision. Some studies reported a low rate of adverse events, and no significant risks were found with resistance exercises, making them a safe option for improving physical fitness. ^{6 7 8 9 10}

How is the Exercise Intervention treatment for Carotid Stenosis and Mobility Impairment different from other treatments?

The Exercise Intervention treatment is unique because it combines aerobic and resistance training to improve mobility and cardiovascular health, which can help manage symptoms and slow disease progression without medication. This approach is particularly beneficial as it addresses both physical fitness and cardiovascular risk factors, unlike standard treatments that may focus solely on medication or surgery. ^{11 12 13 14 15}

What is the purpose of this trial?

Moderate (50-69%) asymptomatic carotid artery stenosis (ACAS) is an important and under-appreciated contributor to balance and mobility dysfunction. This is significant because declines in balance and mobility are a significant predictor of falls, disability, loss of independence, and death in older adults. Further, falls and fall-related injuries in older adults cost approximately 50 billion dollars annually in the United States, and are the leading cause of adverse events reported by the Veterans Health Administration. This proposal seeks to: 1) investigate the impact of a supervised aerobic and challenging balance exercise program on balance and mobility function in patients with moderate ACAS; and 2) elucidate whether these changes are related to changes in cerebral perfusion. With 830,000 Veterans estimated to have moderate ACAS and at risk for balance and mobility dysfunction and increased falls, the findings from this study could have significant impacts on the clinical management, quality of life, and functional independence of Veterans with moderate ACAS.

Research Team

Sarasijhaa Desikan, MD

Principal Investigator

Baltimore VA Medical Center VA Maryland Health Care System, Baltimore, MD

Eligibility Criteria

This trial is for adults over 18 with moderate (50-69%) asymptomatic carotid artery stenosis, confirmed by medical history and imaging tests. It's not for those with Parkinson's, severe depression, recent strokes or TIA, planned carotid surgery, exercise restrictions from doctors, or who already do regular structured aerobic exercise.

Inclusion Criteria

The severity of narrowing in the blood vessels will be checked using ultrasound, magnetic resonance angiography, or CT angiography.

I have no symptoms of carotid stenosis, confirmed by medical exams and the NIH Stroke Scale.

I am 18 or older with a partially blocked carotid artery but no symptoms.

Exclusion Criteria

I experience significant drops in blood pressure when standing up.

I have a blocked or severely narrowed artery in my neck.

I can stand on one leg for 10 seconds without losing balance.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo 12 weeks of supervised aerobic and balance exercises (AeroBal) or standard-of-care vascular risk factor modification

12 weeks

Approximately 36 visits (in-person for exercise group), weekly phone calls for control group

Follow-up

Participants are monitored for changes in balance, mobility, and cerebral perfusion

4 weeks

Treatment Details

Interventions

• Exercise Intervention

Trial Overview The study tests how a supervised program of aerobic and balance exercises affects balance and mobility in patients with moderate asymptomatic carotid stenosis. It also examines if these changes correlate with alterations in brain blood flow.

Participant Groups

Group I: Exercise Intervention Experimental Treatment 1 Intervention

The exercise intervention group will undergo 12 weeks of AeroBal exercise training (approximately 3 times/week). Each exercise session will consist of a 5-minute warm-up walk, approximately 30 minutes of aerobic exercise at a goal of 60-75% HRmax, 15 minutes of balance exercises, and a 5-minute cool-down walk.

Group II: Control Active Control 1 Intervention

The control group will undergo standard-of-care vascular risk factor modification. Control participants will be contacted via telephone on a weekly basis to discuss the importance of vascular risk factor management and adherence to prescribed medical management.

Who Is Running the Clinical Trial?

VA Office of Research and Development

Lead Sponsor

Trials

1,691

Recruited

3,759,000+

Findings from Research

A 12-week home-based cardiac exercise program (HBCEP) significantly improved exercise capacity, serum lipid levels, and self-efficacy in 30 coronary heart disease patients in Turkey, compared to a control group.

The improvements in health outcomes suggest that enhancing self-efficacy through educational sessions and goal-setting strategies may play a crucial role in helping patients adhere to exercise programs and reduce cardiac risk factors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of home-based cardiac exercise program on the exercise tolerance, serum lipid values and self-efficacy of coronary patients. Senuzun, F., Fadiloglu, C., Burke, LE., et al.[2019]

In a study of 104 patients with intermittent claudication, both upper-limb and lower-limb aerobic exercise training significantly improved disease-specific functional status and health-related quality of life compared to a non-exercise control group.

After 24 weeks, the upper-limb exercise group showed improvements in all domains of the Walking Impairment Questionnaire, while the lower-limb group showed improvements in three out of four domains, indicating that both forms of exercise can be effective in managing symptoms of claudication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Upper- versus lower-limb aerobic exercise training on health-related quality of life in patients with symptomatic peripheral arterial disease. Saxton, JM., Zwierska, I., Blagojevic, M., et al.[2015]

In a study of 28 heart failure patients, both low-volume time-based resistance exercise training (TRE) and aerobic moderate-intensity cycling (AMC) significantly improved exercise capacity and health-related quality of life after 6 weeks, with no differences between the two methods.

TRE required less time and energy expenditure compared to AMC, suggesting it could be a more time-efficient option for encouraging exercise adherence in patients with heart failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative Effectiveness of Low-Volume Time-Efficient Resistance Training Versus Endurance Training in Patients With Heart Failure. Munch, GW., Rosenmeier, JB., Petersen, M., et al.[2019]

Both low-intensity and high-intensity exercise rehabilitation programs significantly improved physical function and health-related quality of life in patients with peripheral arterial disease (PAD), with similar outcomes after 6 months of training.

Patients in both groups experienced a remarkable increase in claudication distance (over 100% improvement), indicating that low-intensity exercise can be as effective as high-intensity exercise for enhancing functional independence in PAD patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of exercise intensity on the response to exercise rehabilitation in patients with intermittent claudication. Gardner, AW., Montgomery, PS., Flinn, WR., et al.[2022]

In a study of 35 patients with intermittent claudication, 12 weeks of treadmill-only exercise training led to an increase in homocysteine levels, indicating a potential negative impact on systemic inflammation, while the combination of treadmill and resistance training did not show this increase.

The combination training group exhibited a rise in neutrophil elastase levels, suggesting a different inflammatory response, and showed varying cytokine expressions compared to the treadmill-only group, highlighting the complex immune-modulatory effects of different exercise regimens on inflammation in patients with atherosclerosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomised controlled trial of two supervised exercise regimens and their impact on inflammatory burden in patients with intermittent claudication. Delaney, CL., Spark, JI.[2017]

High-intensity interval training (HIIT) is as effective, if not more so, than traditional moderate-intensity continuous training (MICT) for patients with cardiovascular disease, based on a systematic review of 23 studies involving 1117 participants.

The safety profile of HIIT in cardiac rehabilitation is promising, with only one major cardiovascular adverse event reported per 17,083 training sessions, indicating that HIIT can be safely implemented in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-Intensity Interval Training for Patients With Cardiovascular Disease-Is It Safe? A Systematic Review. Wewege, MA., Ahn, D., Yu, J., et al.[2021]

A 10-week circuit weight training program was found to be safe for patients aged 35 to 70 with coronary artery disease, showing no adverse cardiovascular events during the study.

Participants in the circuit weight training group significantly improved their treadmill performance and strength, with treadmill time increasing from 619 to 694 seconds and an average strength increase of 24%, while the control group showed no changes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Circuit weight training in cardiac patients. Kelemen, MH., Stewart, KJ., Gillilan, RE., et al.[2019]

A systematic review of 11 studies involving 156 clinically stable patients with cardiometabolic diseases found that high-intensity interval exercise (HIIE) can lead to adverse responses in about 8% of individuals, indicating a higher risk compared to moderate-intensity exercise.

It is recommended that patients with cardiometabolic diseases who wish to engage in HIIE should be clinically stable, have prior experience with moderate-intensity exercise, and exercise under supervision to ensure safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

What Doesn't Kill You Makes You Fitter: A Systematic Review of High-Intensity Interval Exercise for Patients with Cardiovascular and Metabolic Diseases. Levinger, I., Shaw, CS., Stepto, NK., et al.[2022]

A mixed interval-type aerobic and strength training program (MIAST) significantly improved physical fitness in patients with stable coronary artery disease (CAD), with notable increases in peak oxygen uptake (6.9%) and exercise time (11.2%) after 12 weeks of training.

The MIAST program was safe and well-tolerated, showing no adverse effects, while also enhancing muscle strength (19.9%) and potentially improving metabolic health by decreasing inflammation-related gene expression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of aerobic and strength training on aerobic capacity, muscle strength, and gene expression of lymphomonocytes in patients with stable CAD. Lehti, M., Valkeinen, H., Sipilä, S., et al.[2020]

Resistance exercises are safe and effective for patients with coronary artery disease (CAD), post-myocardial infarction (MI), and those who have undergone coronary artery bypass grafting (CABG), as shown in a review of 11 studies from 1997 to 2007.

The benefits of resistance training include improved muscular strength, increased physical capacity, and enhanced emotional well-being and quality of life, with no reported risks associated with the exercises.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Resistance exercises for health promotion in coronary patients: evidence of benefits and risks. Oliveira, JL., Galvão, CM., Rocha, SM.[2011]

A review of 13 trials involving 1440 participants identified that successful exercise interventions for neurogenic claudication due to lumbar spinal stenosis often included components like stretches, strength training, and aerobic exercises, particularly cycling.

Most interventions featured supervision and flexion-based exercises, but balance exercises were rarely included, suggesting that a diverse approach may enhance the effectiveness of treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exercise treatments for lumbar spinal stenosis: A systematic review and intervention component analysis of randomised controlled trials. Comer, C., Williamson, E., McIlroy, S., et al.[2023]

A short-course supervised physical training program significantly improved walking distances and reduced recovery times in patients with intermittent claudication, with notable increases in initial and absolute claudication distances after just 18 days of training.

The training protocol was cost-effective, achieving similar benefits to longer programs while minimizing costs, demonstrating that tailored exercise can effectively manage intermittent claudication without increasing the risk of inflammation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness and costs of a short-course supervised training program in claudicants: proposal for a shared protocol with aerobic working load. Andreozzi, GM., Leone, A., Martini, R., et al.[2008]

Incorporating lifestyle interventions, particularly moderate-intensity exercise, alongside pharmacological therapy is crucial for preventing further cardiovascular diseases, as recommended by the American Heart Association and American College of Sports Medicine.

Regular exercise (30-40 minutes, four to five times a week) can significantly improve cardiovascular health by enhancing risk factors like dyslipoproteinemia and insulin resistance, normalizing endothelial function, and slowing down atherosclerosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Physical exercise in secondary prevention of coronary heart disease]. Shutt, A., Bolotova, EV., Khalle, M.[2017]

In a study of 26 patients recovering from heart surgeries, subjective measures of exercise tolerance improved consistently over 12 weeks, while objective measures like power output showed slower recovery, taking up to 21 weeks to reach 85% of predicted levels.

The findings highlight the importance of assessing both objective (like power output) and subjective (like self-efficacy and quality of life) measures in rehabilitation programs, as their recovery timelines differ significantly.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Time course of recovery during cardiac rehabilitation. Foster, C., Oldridge, NB., Dion, W., et al.[2019]

A six-month supervised exercise program combining aerobic and resistance training significantly improved walking ability and lower limb body composition in patients with peripheral arterial disease (PAD) and intermittent claudication, compared to a control group.

Patients in the exercise program experienced major improvements in claudication onset time and distance, as well as increases in fat-free mass and predicted muscle mass, highlighting the efficacy of this combined exercise approach in managing PAD symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Six-month effects of supervised exercise on walking ability and health-related factors in peripheral arterial disease: a pilot study. Machado, I., Ferreira, J., Magalhães, C., et al.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

Effects of home-based cardiac exercise program on the exercise tolerance, serum lipid values and self-efficacy of coronary patients. [2019]

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

Upper- versus lower-limb aerobic exercise training on health-related quality of life in patients with symptomatic peripheral arterial disease. [2015]

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

Comparative Effectiveness of Low-Volume Time-Efficient Resistance Training Versus Endurance Training in Patients With Heart Failure. [2019]

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

The effect of exercise intensity on the response to exercise rehabilitation in patients with intermittent claudication. [2022]

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

A randomised controlled trial of two supervised exercise regimens and their impact on inflammatory burden in patients with intermittent claudication. [2017]

6. England pubmed.ncbi.nlm.nih.gov

High-Intensity Interval Training for Patients With Cardiovascular Disease-Is It Safe? A Systematic Review. [2021]

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

Circuit weight training in cardiac patients. [2019]

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

What Doesn't Kill You Makes You Fitter: A Systematic Review of High-Intensity Interval Exercise for Patients with Cardiovascular and Metabolic Diseases. [2022]

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

Effects of aerobic and strength training on aerobic capacity, muscle strength, and gene expression of lymphomonocytes in patients with stable CAD. [2020]

10. Australia pubmed.ncbi.nlm.nih.gov

Resistance exercises for health promotion in coronary patients: evidence of benefits and risks. [2011]

11. England pubmed.ncbi.nlm.nih.gov

Exercise treatments for lumbar spinal stenosis: A systematic review and intervention component analysis of randomised controlled trials. [2023]

12. Italy pubmed.ncbi.nlm.nih.gov

Effectiveness and costs of a short-course supervised training program in claudicants: proposal for a shared protocol with aerobic working load. [2008]

13. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Physical exercise in secondary prevention of coronary heart disease]. [2017]

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

Time course of recovery during cardiac rehabilitation. [2019]

15. Italy pubmed.ncbi.nlm.nih.gov

Six-month effects of supervised exercise on walking ability and health-related factors in peripheral arterial disease: a pilot study. [2023]