Exercise & Supplements for Chronic Kidney Disease

(NeurovEx Trial)

Recruiting at2 trial locations

Overseen by Joe Nocera, PhD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Emory University

Must not be taking: Central alpha agonists, MAO inhibitors

Disqualifiers: Severe CKD, Drug abuse, Heart disease, others

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial aims to see if regular cycling exercise, a medication called Kuvan, and common sports supplements can help people with chronic kidney disease improve their exercise ability and manage blood pressure during exercise.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are currently taking central alpha agonists (like clonidine) or monoamine oxidase (MAO) inhibitors.

What evidence supports the effectiveness of exercise and supplements as a treatment for chronic kidney disease?

Research shows that aerobic and resistance exercises can help people with chronic kidney disease by reducing inflammation, improving insulin sensitivity, and increasing muscle strength. These exercises may also improve kidney function and overall quality of life, making them beneficial for managing the condition. ^{1 2 3 4 5}

Is exercise and supplementation safe for people with chronic kidney disease?

Exercise, including aerobic and resistance training, appears to be safe for people with chronic kidney disease, as no cardiac events were reported in the studies reviewed. However, combining resistance training with L-arginine supplementation in an animal study did not show the same benefits as exercise alone, suggesting caution with certain supplements. ^{1 3 6 7 8}

How does the treatment of exercise and supplements for chronic kidney disease differ from other treatments?

This treatment is unique because it combines exercise training with supplements like 6R-BH4, histidine, and beta-alanine, which may improve muscle strength, exercise capacity, and overall quality of life in CKD patients. Unlike standard treatments that focus solely on medication, this approach integrates physical activity and nutritional support to address multiple aspects of the disease. ^{1 3 5 9 10}

Research Team

Joe Nocera, PhD

Principal Investigator

Emory University

Eligibility Criteria

This trial is for adults with moderate to severe chronic kidney disease (stages III or IV), which means their kidneys don't filter blood well. They should have stable kidney function without major changes in the last 3 months and not be regular exercisers, working out less than 40 minutes per week.

Inclusion Criteria

My kidney function is moderately to severely reduced.

My kidney function has been stable, with less than a 30% drop in efficiency.

Does not exercise regularly (defined as exercising less than 20 minutes twice per week)

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Baseline Assessment

Measurement of vein constriction response to adrenaline, muscle pH, and muscle oxygenation in CKD patients versus controls

1-2 weeks

1-2 visits (in-person)

Treatment

Participants undergo exercise training or stretching, with or without 6R-BH4 or histidine and beta-alanine supplementation, 3 times per week

6-14 weeks

18-42 visits (in-person)

Follow-up

Participants are monitored for changes in muscle oxygenation, vascular responsiveness, and blood pressure response during exercise

4 weeks

2 visits (in-person)

Treatment Details

Interventions

• 6R-BH4 (Drug)
• Exercise training (Behavioural Intervention)
• Histidine and beta-alanine supplementation (Dietary Supplement)

Trial Overview The study looks at why patients with CKD struggle with exercise and high blood pressure during it. It tests if cycling, a drug called Kuvan (6R-BH4), or supplements like histidine and beta-alanine can help improve these issues. Some participants will receive placebos instead of actual drugs.

Participant Groups

Group I: Exercise training + 6R-BH4 Experimental Treatment 3 Interventions

Participants randomized to this arm will exercise on a stationary bicycle for 20-45 minutes, 3 times per week, for 6-12 weeks. This arm will also take the study drug 6R-BH4.

Group II: Exercise training + histidine and beta-alanine Active Control 2 Interventions

Participants randomized to this arm will exercise on a stationary bicycle for 20-45 minutes, 3 times per week, for 6-12 weeks. This arm will also take histidine and beta-alanine supplementation.

Group III: Exercise training + histidine and beta-alanine placebo Active Control 2 Interventions

Participants randomized to this arm will exercise on a stationary bicycle for 20-45 minutes, 3 times per week, for 6-12 weeks. This arm will also take a placebo to match the histidine and beta-alanine supplementation.

Group IV: Exercise training + 6R-BH4 placebo Active Control 3 Interventions

Participants randomized to this arm will exercise on a stationary bicycle for 20-45 minutes, 3 times per week, for 6-12 weeks. This arm will also take a placebo to match the study drug 6R-BH4.

Group V: Stretching + 6R-BH4 Active Control 3 Interventions

Participants randomized to this arm will do muscle stretching and toning for 20-45 minutes, 3 times per week, for 6-12 weeks. This arm will also take the study drug 6R-BH4.

Group VI: Stretching + placebo Placebo Group 3 Interventions

Participants randomized to this arm will do muscle stretching and toning for 20-45 minutes, 3 times per week, for 6-12 weeks. This arm will also take a placebo instead of the active study drug.

Who Is Running the Clinical Trial?

Emory University

Lead Sponsor

Trials

1,735

Recruited

2,605,000+

Dr. R. Donald Harvey

Emory University

Chief Medical Officer

MD from Emory University School of Medicine

Dr. George Painter

Emory University

Chief Executive Officer since 2013

PhD in Synthetic Organic Chemistry from Emory University

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Dr. Gary H. Gibbons

National Heart, Lung, and Blood Institute (NHLBI)

Chief Executive Officer since 2012

MD from Harvard Medical School

Dr. James P. Kiley

National Heart, Lung, and Blood Institute (NHLBI)

Chief Medical Officer since 2011

MD from University of California, San Francisco

Findings from Research

Aerobic exercise and resistance training can significantly improve health outcomes in chronic kidney disease (CKD) patients by reducing inflammation, increasing insulin sensitivity, and potentially enhancing kidney function, as evidenced by improvements in glomerular filtration rate (GFR) and reductions in microalbuminuria.

Combining both aerobic and resistance training during dialysis has been shown to enhance muscle strength, physical functionality, and overall quality of life, suggesting that exercise could be a vital component in the management and prevention of CKD progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparison of aerobic exercise and resistance training in patients with and without chronic kidney disease. Moinuddin, I., Leehey, DJ.[2022]

Aerobic exercise interventions have been shown to improve physical functioning and performance in patients with chronic kidney disease (CKD), with evidence suggesting benefits for blood pressure control, lipid profiles, and mental health.

Despite the known safety and benefits of exercise for CKD patients, many remain inactive, highlighting the need for better assessment and encouragement of physical activity, particularly through low-intensity resistance and aerobic training programs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exercise and chronic kidney disease: current recommendations. Johansen, KL.[2022]

A 1-year cardiac rehabilitation program showed no overall significant changes in renal function markers for patients with cardiovascular disease, but those with mild-to-moderate chronic kidney disease (CKD) experienced a notable improvement in their estimated glomerular filtration rate (eGFR).

This suggests that cardiac rehabilitation may be beneficial for enhancing renal function specifically in patients with mild-to-moderate CKD, highlighting the potential for exercise training as a supportive therapy in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influence of a Cardiac Rehabilitation Program on Renal Function in Patients With Cardiovascular Disease in a One-Year Follow-Up. Fujimi, K., Miura, SI., Matsuda, T., et al.[2020]

Nutritional interventions are well-supported in managing chronic kidney disease (CKD) and are included in many clinical practice guidelines, highlighting their importance in treatment.

Progressive resistance training (PRT) has been shown to be safe and effective in improving clinical and functional outcomes for patients with CKD, despite having a more limited evidence base compared to aerobic exercise.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Progressive resistance training and nutrition in renal failure. Chan, M., Cheema, BS., Fiatarone Singh, MA.[2010]

Patients with chronic kidney disease (CKD) who are on dialysis typically have low exercise capacity and physical functioning, but regular exercise training can significantly improve these aspects.

Despite the clear benefits of exercise for CKD patients, the nephrology community has not yet integrated exercise recommendations into standard care practices, highlighting a need for better implementation of exercise counseling in treatment plans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Implementing exercise: what do we know? Where do we go? Painter, P.[2022]

Aerobic exercise training can enhance exercise capacity in patients with chronic kidney disease (CKD), while resistance training may improve muscle function, based on a review of 6 trials involving 131 participants.

The review found no reported cardiac events during exercise training, indicating that exercise is a safe intervention for individuals with CKD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Exercise Training on Delaying Disease Progression in Patients with Chronic Kidney Disease: a Review of the Literature. Izumi, A., Kitamura, M., Izawa, KP.[2019]

In a study of 26 chronic kidney disease patients, blood flow restriction training led to significant increases in the diameter of the radial artery, indicating potential benefits for vascular health, but did not outperform conventional exercise without blood flow restriction.

Both blood flow restriction and control groups showed increases in cephalic vein diameter, suggesting that physical training is beneficial for vascular adaptations in patients with arteriovenous fistulas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Does blood flow restriction training increase the diameter of forearm vessels in chronic kidney disease patients? A randomized clinical trial. Barbosa, JB., Maia, TO., Alves, PS., et al.[2019]

Resistance training (RT) significantly improved muscle strength, renal function, and reduced renal fibrosis in a rat model of chronic kidney disease (CKD) over a 10-week period.

However, when combined with oral L-arginine (L-arg) supplementation, the benefits of RT were negated, indicating that L-arg may interfere with the positive effects of exercise on CKD outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

l-Arginine supplementation blunts resistance exercise improvement in rats with chronic kidney disease. Souza, MK., Moraes, MR., Rosa, TS., et al.[2019]

Exercise training significantly improves maximal exercise capacity, muscle strength, and endurance in patients with chronic kidney disease (CKD) across all stages, including those on dialysis and post-transplant.

Starting exercise training during the predialysis stage is ideal, as it helps combat muscle catabolism, weight loss, and enhances overall quality of life, making it a crucial part of CKD patient care prescribed by nephrologists.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Physical working capacity and muscle strength in chronic renal failure are improved by exercise]. Clyne, N.[2006]

An exercise program combining supervised training and home-based training significantly improved physical fitness in patients with chronic kidney disease (CKD), as shown by increased metabolic equivalent tasks (METs) and 6-minute walk distance after 10 months.

The study found no serious adverse events related to the exercise training, indicating that this intervention is safe for patients with CKD, although the study was not specifically designed to assess safety outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exercise training in CKD: efficacy, adherence, and safety. Howden, EJ., Coombes, JS., Strand, H., et al.[2022]

References

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

A comparison of aerobic exercise and resistance training in patients with and without chronic kidney disease. [2022]

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

Exercise and chronic kidney disease: current recommendations. [2022]

3. Canada pubmed.ncbi.nlm.nih.gov

Influence of a Cardiac Rehabilitation Program on Renal Function in Patients With Cardiovascular Disease in a One-Year Follow-Up. [2020]

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

Progressive resistance training and nutrition in renal failure. [2010]

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

Implementing exercise: what do we know? Where do we go? [2022]

6. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Effects of Exercise Training on Delaying Disease Progression in Patients with Chronic Kidney Disease: a Review of the Literature. [2019]

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

Does blood flow restriction training increase the diameter of forearm vessels in chronic kidney disease patients? A randomized clinical trial. [2019]

8. Netherlands pubmed.ncbi.nlm.nih.gov

l-Arginine supplementation blunts resistance exercise improvement in rats with chronic kidney disease. [2019]

9. Sweden pubmed.ncbi.nlm.nih.gov

[Physical working capacity and muscle strength in chronic renal failure are improved by exercise]. [2006]

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

Exercise training in CKD: efficacy, adherence, and safety. [2022]