Sodium Bicarbonate for Chronic Kidney Disease

(Senergy-CKD Trial)

Recruiting at 1 trial location

Overseen By Baback Roshanravan, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of California, Davis

Must not be taking: Insulin

Disqualifiers: Diabetes, Hyperkalemia, Heart disease, others

Prior Safety Data This treatment has passed at least one previous human trial

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

Compensation: Varies

Number of Visits: 8

Duration: 16 weeks

80 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you have type 2 diabetes managed with insulin, you cannot participate in the trial.

What data supports the effectiveness of the drug Sodium Bicarbonate for Chronic Kidney Disease?

Sodium bicarbonate is commonly used to treat metabolic acidosis (a condition where the body produces too much acid or the kidneys are not removing enough acid) in chronic kidney disease. It is considered a mainstay treatment for this condition, although concerns exist about administering sodium to patients with high blood pressure or sodium retention issues. ^{1 2 3 4 5}

Is sodium bicarbonate safe for use in humans?

The research articles provided do not contain specific safety data on sodium bicarbonate for chronic kidney disease or other conditions. ^{6 7 8 9 10}

How is the drug sodium bicarbonate unique in treating chronic kidney disease?

Sodium bicarbonate is unique in treating chronic kidney disease because it helps correct metabolic acidosis (a condition where the body produces too much acid or the kidneys do not remove enough acid) by increasing bicarbonate levels in the blood. It is often administered orally in a form that resists stomach acid, which helps prevent early release and potential side effects. ^{1 5 11 12 13}

What is the purpose of this trial?

Skeletal muscle metabolic health is critical for mobility and an underrecognized target of metabolic acidosis in chronic kidney disease. Impaired muscle mitochondrial metabolism underlies poor physical endurance increasing the risk of mobility disability. The proposed project will use precise in vivo tools to study the pathophysiology of poor physical endurance in a clinical trial treating metabolic acidosis among persons living with chronic kidney disease.

Research Team

Jorge Gamboa, MD PhD

Principal Investigator

Vanderbilt University

Baback Roshanravan, MD

Principal Investigator

UC Davis

Eligibility Criteria

This trial is for adults aged 21-85 with moderate to severe chronic kidney disease (CKD) and metabolic acidosis. Participants must have a confirmed eGFR <50ml/min per 1.73m2 and bicarbonate levels below 24 on two occasions. It's not open to those with end-stage liver disease, uncontrolled diabetes or heart issues, mobility disabilities, dementia, non-English speakers, or certain medical implants.

Inclusion Criteria

My kidney function is low, confirmed by tests.

Your blood has low levels of bicarbonate on two separate tests.

I am between 21 and 85 years old.

Exclusion Criteria

You have had an organ transplant in the past.

You have a history of high potassium levels (K>5.4).

I cannot walk without someone helping me.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive sodium bicarbonate or placebo for 16 weeks to assess muscle metabolic health and physical endurance

16 weeks

Visits every 8 weeks for capsule dispensing

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Sodium Bicarbonate

Trial Overview The study tests whether sodium bicarbonate can improve muscle mitochondrial metabolism and physical endurance in CKD patients by treating metabolic acidosis. Participants will receive either sodium bicarbonate or a placebo to compare effects on their skeletal muscle health.

Participant Groups

Group I: Sodium bicarbonate 16 weeks Experimental Treatment 1 Intervention

Sodium bicarbonate will be dosed at 0.8meq per kilogram of ideal body weight daily (1meq is approximately 84mg). We will use the Devine formula to determine ideal body weight. Investigational Drug Services at both UC Davis and Vanderbilt will compound the sodium bicarbonate. Sodium bicarbonate 650 mg tablets will be over-encapsulated and matching placebo capsules will be prepared. Participants will be limited to a maximum of 9 capsules daily (maximum dose = 5850mg of sodium bicarbonate). Capsules will be dispensed to patients in two separate 8-week allotments. The dose will be rounded to the nearest whole capsule and depending on participant preference may be divided into portions taken twice or thrice daily. Given the high probability of interruption in sodium bicarbonate supply and availability, we may need to change brands of sodium bicarbonate intermittently.

Group II: placebo 16 weeks Placebo Group 1 Intervention

Microcrystalline cellulose

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?

University of California, Davis

Lead Sponsor

Trials

958

Recruited

4,816,000+

Vanderbilt University Medical Center

Collaborator

Trials

922

Recruited

939,000+

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Collaborator

Trials

2,513

Recruited

4,366,000+

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]

Veverimer is a novel treatment for metabolic acidosis in chronic kidney disease that increases serum bicarbonate levels without adding sodium, making it safer for patients with hypertension or sodium retention.

The drug has shown positive effects on physical functioning and a good safety profile, but some unexpected results, such as a lack of dose dependency in bicarbonate increase and an isochloremic effect, suggest that further research is needed to fully understand its mechanism of action.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Veverimer: An Emerging Potential Treatment Option for Managing the Metabolic Acidosis of CKD. Adrogué, HJ., Madias, NE.[2020]

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]

In a study of 72 frail elderly patients undergoing CT colonography with sodium picosulphate-magnesium citrate (SPS-MC), no significant changes in key renal function markers or electrolytes were observed post-procedure, indicating safety in this population.

While a mild increase in serum magnesium was noted in some patients, it did not lead to any clinical issues, suggesting that CTC with SPS-MC is effective for bowel preparation, though caution is advised for those with decreased renal function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bowel preparation in CT colonography: electrolyte and renal function disturbances in the frail and elderly patient. Mc Laughlin, P., Eustace, J., Mc Sweeney, S., et al.[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]

In a study of 173 patients undergoing colonoscopy, the novel 1-L PEG+Asc bowel preparation was found to be non-inferior to the standard PEG+SPMC preparation, with 89% of patients achieving successful bowel preparation compared to 85.4% in the PEG+SPMC group.

While more patients using 1-L PEG+Asc reported moderate to severe nausea, overall tolerability was similar between the two preparations, suggesting that 1-L PEG+Asc is an effective alternative for bowel preparation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Split-dose 1 L polyethylene glycol (PEG) with ascorbate is non-inferior to split-dose PEG with sodium picosulfate and magnesium citrate with similar tolerability: a randomized study. Nalankilli, K., Gibson, DJ., Anwar, S., et al.[2022]

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]

In a study of 144 chronic kidney disease (CKD) patients, 34% were found to have metabolic acidosis (MA-CKD), indicating a significant prevalence of this condition among those with advanced CKD.

Only 16% of patients with MA-CKD were prescribed oral sodium bicarbonate (OSB) for treatment, while the majority were managed with dietary changes, highlighting a need for greater awareness of the benefits of OSB in managing MA-CKD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Prevalence and Management of Metabolic Acidosis of Chronic Kidney Disease Ahmed, AR., Satti, MM., Abdalla, AE., et al.[2020]

In a study involving 20 patients with end-stage renal failure undergoing chronic acetate hemodialysis, oral administration of 6-9 g of sodium bicarbonate for 6 weeks successfully corrected chronic renal acidosis.

The treatment normalized the acid-base status between dialysis sessions without causing major side effects, indicating it is a safe and effective intervention for managing acidosis in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Effects of improved levels of plasma bicarbonates in terminal renal failure]. Melamed, J., Kramer, I., Kuhlencordt, M., et al.[2013]

In a study involving 300 older adults with advanced chronic kidney disease, oral sodium bicarbonate did not show significant improvements in physical function or quality of life compared to a placebo after 12 months.

The treatment was associated with higher costs and more adverse events, suggesting that oral sodium bicarbonate is unlikely to be cost-effective for this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sodium bicarbonate to improve physical function in patients over 60 years with advanced chronic kidney disease: the BiCARB RCT. Witham, MD., Band, M., Chong, H., et al.[2021]

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

Veverimer: An Emerging Potential Treatment Option for Managing the Metabolic Acidosis of CKD. [2020]

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. Germany pubmed.ncbi.nlm.nih.gov

Bowel preparation in CT colonography: electrolyte and renal function disturbances in the frail and elderly 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. Australia pubmed.ncbi.nlm.nih.gov

Split-dose 1 L polyethylene glycol (PEG) with ascorbate is non-inferior to split-dose PEG with sodium picosulfate and magnesium citrate with similar tolerability: a randomized study. [2022]

9. Switzerland pubmed.ncbi.nlm.nih.gov

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

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

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

11. Ireland pubmed.ncbi.nlm.nih.gov

The Prevalence and Management of Metabolic Acidosis of Chronic Kidney Disease [2020]

12. Switzerland pubmed.ncbi.nlm.nih.gov

[Effects of improved levels of plasma bicarbonates in terminal renal failure]. [2013]

13. England pubmed.ncbi.nlm.nih.gov

Sodium bicarbonate to improve physical function in patients over 60 years with advanced chronic kidney disease: the BiCARB RCT. [2021]