Exercise for Chronic Kidney Disease

(Sym-CKD Trial)

Overseen By Jeanie Park, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Emory University

Must not be taking: Central alpha agonists, MAOIs

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 6-12 weeks

110 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, specifically central alpha agonists like clonidine and monoamine oxidase inhibitors (MAOIs).

What data supports the effectiveness of sodium bicarbonate as a drug for chronic kidney disease?

Research indicates that sodium bicarbonate is used as an oral medication for chronic kidney disease and is considered a physiological alkalinizing agent, which can help manage metabolic acidosis, a common issue in kidney disease. ^{1 2 3 4 5}

Is exercise generally safe for people with chronic kidney disease?

The research articles provided do not contain specific safety information about exercise for chronic kidney disease. However, they discuss the safety of polyethylene glycol solutions used for colonoscopy preparation, which are generally safe but can cause minor side effects like nausea and cramps. Exercise is generally considered safe for most people, but it's always best to consult with a healthcare provider before starting any new exercise program, especially for those with chronic conditions. ^{6 7 8 9 10}

How does the drug Sodium Bicarbonate differ from other treatments for chronic kidney disease?

Sodium Bicarbonate is unique for chronic kidney disease as it helps neutralize acid in the blood, which can be beneficial for kidney function. Unlike other treatments that focus on exercise or physical activity to improve kidney health, Sodium Bicarbonate directly addresses metabolic acidosis, a common issue in chronic kidney disease. ^{11 12 13 14 15}

What is the purpose of this trial?

The purpose of this study is to find out why patients with chronic kidney disease (CKD) have poor exercise capacity and what causes an increase in blood pressure during exercise (i.e. increased adrenaline levels, or decreased ability of blood vessels to dilate).

Research Team

Jeanie Park, MD

Principal Investigator

Emory University

Eligibility Criteria

This trial is for veterans aged 18-75 with Stage III or IV Chronic Kidney Disease who exercise less than 40 minutes per week. It's also open to similar-aged veterans without kidney disease as controls. Participants must be able to follow the study plan and ride a stationary bike, but can't join if they have severe CKD, certain blood chemistry imbalances, drug/alcohol abuse issues, diabetic neuropathy, serious diseases affecting survival chances, severe anemia or heart problems.

Inclusion Criteria

Willing and able to cooperate with the protocol

You exercise for less than 20 minutes, two times a week.

I am a veteran with advanced chronic kidney disease.

Exclusion Criteria

My blood pressure is not higher than 170/100 mmHg.

I am currently taking medication like clonidine.

Your blood pressure is too low, less than 100/50 mmHg.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo exercise training or stretching with sodium bicarbonate or placebo for 6-12 weeks

6-12 weeks

3 visits per week (in-person)

Follow-up

Participants are monitored for changes in muscle interstitial pH and venoconstriction after exercise

4 weeks

Treatment Details

Interventions

• Exercise Training
• Placebo
• Sodium Bicarbonate
• Stretching

Trial Overview The study aims to understand why patients with chronic kidney disease struggle with physical activity and experience high blood pressure during it. It tests how stretching exercises compare against no exercise (control), the effects of sodium bicarbonate supplementation versus placebo, and the benefits of regular exercise training.

Participant Groups

Group I: Control to Exercise (Stretching) plus Sodium Bicarbonate Active Control 2 Interventions

Subjects with CKD will undergo progressive whole body stretching and toning exercises 3 times a week for 20-45 minutes for 6-12 weeks. Additionally, subjects will take 1300-2600 mg (2-4 pills) of sodium bicarbonate prior to each stretching session three times a week.

Group II: Exercise Training plus Sodium Bicarbonate Active Control 2 Interventions

Subjects with CKD will undergo exercise training on a stationary bicycle for 20-45 minutes, 3 times per week, for 6-12 weeks. Additionally, subjects will take 1300-2600 mg (2-4 pills) of sodium bicarbonate prior to each exercise session three times a week.

Group III: Exercise Training plus Placebo Active Control 2 Interventions

Subjects with CKD will undergo exercise training on a stationary bicycle,for 20-45 minutes, 3 times per week, for 6-12 weeks. Additionally, subjects will take 2-4 placebo tablets prior to each exercise session three times a week.

Group IV: Healthy Control Active Control 1 Intervention

Healthy subjects without CKD will not receive any interventions.

Group V: Control to Exercise (Stretching) plus Placebo Placebo Group 2 Interventions

Subjects with CKD will undergo progressive whole body stretching and toning exercises 3 times a week for 20-45 minutes for 6-12 weeks. Additionally, subjects will take 2-4 placebo tablets prior to each exercise session three times a week.

Sodium Bicarbonate is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Sodium Bicarbonate for:

• Metabolic acidosis
• Heartburn
• Acid indigestion
• Upset stomach
• Severe renal disease
• Circulatory insufficiency due to shock

Approved in European Union as Sodium Bicarbonate for:

• Metabolic acidosis
• Heartburn
• Acid indigestion
• Upset stomach
• Severe renal disease
• Circulatory insufficiency due to shock

Approved in Canada as Sodium Bicarbonate for:

• Metabolic acidosis
• Heartburn
• Acid indigestion
• Upset stomach
• Severe renal disease
• Circulatory insufficiency due to shock

Who Is Running the Clinical Trial?

Emory University

Lead Sponsor

Trials

1,735

Recruited

2,605,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Findings from Research

Sodium bicarbonate products, including bicaNorm and Nephrotrans, are of sufficient pharmaceutical quality, but they release the drug differently at various pH levels, which can lead to potential dose dumping and adverse effects due to carbon dioxide production.

The soft capsule formulation (Nephrotrans) demonstrated the least sodium bicarbonate release at low pH, suggesting it may be a safer and more effective option compared to enteric-coated tablets and pellet formulations, aligning with reports of adverse effects in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enteric-coated solid dosage forms containing sodium bicarbonate as a drug substance: an exception from the rule? Breitkreutz, J., Gan, TG., Schneider, B., et al.[2014]

In a study of 16 well-nourished patients on maintenance hemodialysis, sevelamer hydrochloride was found to significantly lower serum bicarbonate levels compared to calcium carbonate, indicating a potential worsening of metabolic acidosis during sevelamer treatment.

While both sevelamer and calcium carbonate effectively controlled serum phosphate levels, calcium carbonate maintained serum bicarbonate concentrations within target levels, highlighting its advantage in managing metabolic acidosis in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sevelamer worsens metabolic acidosis in hemodialysis patients. De Santo, NG., Frangiosa, A., Anastasio, P., et al.[2015]

In a study of 32,686 dialysis patients, those treated with sevelamer hydrochloride showed a significantly higher prevalence of severe metabolic acidosis (bicarbonate <15.8 mmol/L), with 16.1% affected at doses of 5.25 g/day or more, compared to only 4.5% in patients not treated with sevelamer.

The analysis revealed a strong negative correlation between the daily dose of sevelamer hydrochloride and serum bicarbonate levels, indicating that higher doses are associated with increased risk of severe acidosis, highlighting the need for careful monitoring of bicarbonate levels in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sevelamer hydrochloride dose-dependent increase in prevalence of severe acidosis in hemodialysis patients: analysis of nationwide statistical survey in Japan. Oka, Y., Miyazaki, M., Matsuda, H., et al.[2015]

In a study involving dogs with induced hemorrhagic shock, a new bicarbonated Ringer's solution (BRS) significantly improved blood base excess values more effectively than lactated Ringer's (LRS) and Ringer's (RS) solutions, indicating its potential for treating metabolic acidosis.

BRS also maintained serum magnesium levels better than other solutions tested, suggesting it is a suitable option for managing electrolyte balance during perioperative care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacological study of BRS, a new bicarbonated Ringer's solution, in haemorrhagic shock dogs. Satoh, K., Ohtawa, M., Katoh, M., et al.[2019]

A proposed study will involve 600 patients with chronic kidney disease (CKD) stages 3b and 4 to assess whether sodium bicarbonate can effectively reduce renal death and cardiovascular mortality by correcting metabolic acidosis.

The study aims to compare outcomes between a bicarbonate treatment group and a usual-treatment group, providing crucial data on the potential benefits and risks of alkalinizing agents in pre-end-stage renal disease patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A prospective, multicenter, randomized, controlled study: the correction of metabolic acidosis with use of bicarbonate in Chronic Renal Insufficiency (UBI) Study. Di Iorio, B., Aucella, F., Conte, G., et al.[2013]

Polyethylene glycol with electrolytes (PEG-ELS, Golytely) is generally safe for use in both adults and children for colonic preparation and treatment of severe chronic constipation, with minimal side effects like nausea and abdominal cramps.

However, a case report highlights a serious risk when Golytely is improperly prepared for pediatric patients, leading to severe electrolyte disturbances and a tragic outcome, emphasizing the importance of correct preparation and administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lethal Complication From Inappropriately Prepared Polyethylene Glycol (Golytely) in a Pediatric Patient. Skaff, C., Alayed, T.[2021]

In a study involving 136 patients, the combination of 238 g of polyethylene glycol (PEG) with 1.9 L of Gatorade was found to be as effective as the traditional 4 L PEG with electrolytes for colonoscopy preparation, with no significant differences in bowel preparation quality.

Patients reported higher satisfaction and experienced fewer adverse effects with the PEG + Gatorade preparation, making it a safer and more tolerable option for those who struggle with the standard PEG-ELS preparation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Colonoscopy preparation: polyethylene glycol with Gatorade is as safe and efficacious as four liters of polyethylene glycol with balanced electrolytes. McKenna, T., Macgill, A., Porat, G., et al.[2021]

Sodium phosphate (NaP) is often considered more effective and better tolerated for bowel preparation before colonoscopy, but it carries significant risks, including severe electrolyte disturbances and potential irreversible renal failure (phosphate nephropathy).

Due to these serious safety concerns, NaP should be prescribed with caution and is recommended to be banned for patients with certain risk factors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Phosphate nephropathy: how to avoid it?]. Bourquin, V., Ponte, B., Zellweger, M., et al.[2013]

Adding two packages of lemon-flavored Kool-Aid drink mix sweetened with aspartame to polyethylene glycol (PEG) colonic lavage solution significantly improved its taste, making it more palatable for patients.

The addition of the drink mix did not significantly alter the osmolality of the PEG solution, ensuring it remained effective for bowel cleansing as per manufacturer specifications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Palatability of colonic lavage solution is improved by the addition of artificially sweetened flavored drink mixes. Gruber, M., Fay, D., Pudhorodsky, T., et al.[2019]

A 1-day bowel preparation using PEG-3350 in pediatric patients for colonoscopy is considered safe, with no clinically significant changes in electrolyte levels or renal function observed in the majority of cases.

However, 24% of patients experienced mild hypokalemia post-prep, and younger children (7 years or younger) showed a higher risk of hypoglycemia, indicating a need for careful monitoring in this age group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of a 1-Day Polyethylene Glycol 3350 Bowel Preparation for Colonoscopy in Children. Sahn, B., Chen-Lim, ML., Ciavardone, D., et al.[2018]

An 8-week intradialytic exercise program for hemodialysis patients led to significant reductions in serum phosphate (by 1.84 mg/dL) and potassium levels (by 0.69 mg/dL), indicating improved electrolyte balance.

The exercise program was found to be safe, with no reported side effects, and serves as an effective complementary treatment for patients with end-stage renal disease undergoing dialysis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of intradialytic aerobic exercise on serum electrolytes levels in hemodialysis patients. Makhlough, A., Ilali, E., Mohseni, R., et al.[2012]

A randomized clinical trial involving 39 hemodialysis patients showed that a cycle ergometer training program significantly improved respiratory function and functional capacity after 24 sessions over eight weeks.

Patients in the treatment group experienced better outcomes in key measures such as forced vital capacity, peak expiratory flow, and performance on the six-minute walk test, indicating that exercise during hemodialysis can enhance overall health in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Functional and Respiratory Capacity of Patients with Chronic Kidney Disease Undergoing Cycle Ergometer Training during Hemodialysis Sessions: A Randomized Clinical Trial. Fernandes, AO., Sens, YADS., Xavier, VB., et al.[2022]

Chronic running exercise significantly improved kidney function in Zucker diabetic fatty (ZDF) rats, evidenced by reduced hyperglycemia, increased insulin secretion, decreased albumin excretion, and normalized creatinine clearance over an 8-week period.

The protective effects of exercise on the kidneys were linked to increased expression of nitric oxide synthase (NOS) and decreased oxidative stress markers, suggesting that regular aerobic exercise could be a beneficial non-drug treatment for early diabetic nephropathy in type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chronic Running Exercise Alleviates Early Progression of Nephropathy with Upregulation of Nitric Oxide Synthases and Suppression of Glycation in Zucker Diabetic Rats. Ito, D., Cao, P., Kakihana, T., et al.[2018]

This nonrandomized trial aims to improve the physical function and quality of life in patients with end-stage kidney disease (ESKD) through various low-intensity exercise programs, highlighting the importance of patient choice in their exercise regimen.

The study will assess the feasibility, safety, and adherence to these exercise interventions over three months, with outcomes including aerobic capacity, quality of life, and long-term clinical results, providing valuable insights into effective strategies for increasing physical activity in ESKD patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Personalized Patient-Centered Intervention to Empower through Physical Activity the Patient in the Dialysis Center: Study Protocol for a Pragmatic Nonrandomized Clinical Trial. Manfredini, F., Lamberti, N., Battaglia, Y., et al.[2021]

The 12-week intradialysis yoga intervention was feasible and safe for patients with end-stage renal disease, with no adverse events reported and a participation frequency of 70%.

While the yoga group had a lower completion rate (72%) compared to the educational program (100%), the study successfully demonstrated the potential for promoting physical activity in this sedentary population, providing important data for future trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility and Safety of Intradialysis Yoga and Education in Maintenance Hemodialysis Patients. Birdee, GS., Rothman, RL., Sohl, SJ., et al.[2018]

References

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

Enteric-coated solid dosage forms containing sodium bicarbonate as a drug substance: an exception from the rule? [2014]

2. Italy pubmed.ncbi.nlm.nih.gov

Sevelamer worsens metabolic acidosis in hemodialysis patients. [2015]

3. Australia pubmed.ncbi.nlm.nih.gov

Sevelamer hydrochloride dose-dependent increase in prevalence of severe acidosis in hemodialysis patients: analysis of nationwide statistical survey in Japan. [2015]

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

Pharmacological study of BRS, a new bicarbonated Ringer's solution, in haemorrhagic shock dogs. [2019]

5. Italy pubmed.ncbi.nlm.nih.gov

A prospective, multicenter, randomized, controlled study: the correction of metabolic acidosis with use of bicarbonate in Chronic Renal Insufficiency (UBI) Study. [2013]

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

Lethal Complication From Inappropriately Prepared Polyethylene Glycol (Golytely) in a Pediatric Patient. [2021]

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

Colonoscopy preparation: polyethylene glycol with Gatorade is as safe and efficacious as four liters of polyethylene glycol with balanced electrolytes. [2021]

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

[Phosphate nephropathy: how to avoid it?]. [2013]

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

Palatability of colonic lavage solution is improved by the addition of artificially sweetened flavored drink mixes. [2019]

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

Safety of a 1-Day Polyethylene Glycol 3350 Bowel Preparation for Colonoscopy in Children. [2018]

11. Iran pubmed.ncbi.nlm.nih.gov

Effect of intradialytic aerobic exercise on serum electrolytes levels in hemodialysis patients. [2012]

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

Functional and Respiratory Capacity of Patients with Chronic Kidney Disease Undergoing Cycle Ergometer Training during Hemodialysis Sessions: A Randomized Clinical Trial. [2022]

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

Chronic Running Exercise Alleviates Early Progression of Nephropathy with Upregulation of Nitric Oxide Synthases and Suppression of Glycation in Zucker Diabetic Rats. [2018]

14. Switzerland pubmed.ncbi.nlm.nih.gov

A Personalized Patient-Centered Intervention to Empower through Physical Activity the Patient in the Dialysis Center: Study Protocol for a Pragmatic Nonrandomized Clinical Trial. [2021]

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

Feasibility and Safety of Intradialysis Yoga and Education in Maintenance Hemodialysis Patients. [2018]