Sodium Bicarbonate for Kidney Stones

Overseen By Sohrab N Ali, M.D

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of California, Irvine

Must be taking: Urocit-K

Must not be taking: Thiazides, ACE inhibitors

Disqualifiers: Pregnancy, Diabetes, Renal dysfunction, others

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

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

Compensation: Varies

Number of Visits: 4

100 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires participants to be currently on Urocit-K therapy, so you will not need to stop this medication. However, if you are taking thiazides or ACE inhibitors, you cannot participate in the trial.

What evidence supports the effectiveness of sodium bicarbonate as a drug for kidney stones?

Sodium bicarbonate is commonly used for urinary alkalization, which can help prevent kidney stones by reducing acidity in urine. However, excessive alkalization may increase the risk of kidney stones, so careful monitoring is necessary. ^{1 2 3 4 5}

Is sodium bicarbonate safe for human use?

Sodium bicarbonate is generally considered safe for human use, but some formulations may cause early drug release in the stomach, leading to potential side effects like gas and discomfort. It's important to use the correct formulation to minimize these risks. ^{1 2 3 6 7}

How does sodium bicarbonate differ from other drugs for kidney stones?

Sodium bicarbonate is used to alkalize urine, which can help prevent kidney stones, and is an alternative for those who cannot tolerate potassium citrate due to side effects or cost. Unlike some other treatments, sodium bicarbonate may increase extracellular volume, which can lead to side effects like weight gain and edema. ^{2 8 9 10 11}

What is the purpose of this trial?

The incidence of kidney stone disease continues to rise globally. Although the treatment of kidney stone disease has dramatically improved in recent years, surgical management remains invasive and expensive. Patients who develop kidney stones are at high risk of recurrence during their lifetime; therefore, prevention of stones should be a primary focus. Low levels of citrate and acidic urine are risk factors for the formation of kidney stones such as calcium oxalate and uric acid, respectively. Calcium oxalate stones are the predominant stone composition in the United States, accounting for over 2/3rds of stones. Citrate is a key inhibitor of calcium oxalate crystal formation and thus increasing it in the urine of a calcium oxalate stone former is quite beneficial. Uric acid stones account for approximately 10 percent of all stone types. These stones form primarily due to an acidic urinary environment which is a prerequisite for crystal formation. Common medications for stone formers include potassium citrate which help to make the urine more alkaline. Although effective, these medications have side effects and may prove to be too expensive (upwards of $450/month). Consuming baking soda (sodium bicarbonate) may prove to be an inexpensive ($0.34/month) equally effective alternative with respect to increasing urinary citrate levels and alkalinizing the urine. Investigators hypothesize that twice a day oral baking soda in a liquid medium (e.g., water, orange juice, soda, etc.) can be an effective, and inexpensive alternative to urocit K with regard to alkalinizing the urine and raising urinary citrate levels.

Research Team

Ralph V Clayman, MD

Principal Investigator

University of California, Irvine

Sohrab N Ali, M.D

Principal Investigator

University of California, Irvine

Eligibility Criteria

This trial is for individuals with kidney stones, specifically those who form stones due to low citrate levels or acidic urine. It's not specified who can't join the trial, but typically participants would need to be in stable health and not have conditions that could interfere with the study.

Inclusion Criteria

I have low urine citrate levels and take Urocit-K for my kidney stones.

Exclusion Criteria

Women who are breastfeeding or plan to breastfeed during study period

I am currently on thiazides or ACE inhibitors.

I have kidney problems, UTI, diabetes, or other listed conditions.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2 weeks

Treatment - Urocit-K

Participants take Urocit-K 30 mEq AM and 30 mEq PM for four weeks, with urine collections and blood tests

4 weeks

2 visits (in-person) for urine collection and blood tests

Washout

Participants undergo a washout period after Urocit-K treatment

2 weeks

Treatment - Baking Soda

Participants take Baking Soda dissolved in water, ½ teaspoon AM and PM for four weeks, with urine collections and blood tests

4 weeks

2 visits (in-person) for urine collection and blood tests

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Sodium Bicarbonate

Trial Overview The study tests if baking soda (sodium bicarbonate) taken twice a day is as effective as potassium citrate at increasing urinary citrate levels and making urine less acidic, which may prevent kidney stone formation.

Participant Groups

Group I: Urocit-K, then Baking Soda Experimental Treatment 2 Interventions

After being off Urocit-K for two weeks, participants will collect two 24-hour urine tests to document hypocitraturia or low urine pH for calcium oxalate or uric acid stone formers, respectively. Participants will take Urocit-K 30 mEq AM and 30 mEq PM for four-weeks. During the last two days of the four-week drug period, two 24-hour urine collections will be obtained, and the participants will enter another washout period of two weeks before switching over to Baking Soda dissolved in up to 250 mL of water ½ teaspoon (29.5 mEq) in AM and ½ Teaspoon (29.5 mEq) in PM for four weeks. During the last two days of this study arm, two 24-hour urine collections will be obtained. A basic metabolic panel blood test will be obtained at the end of the study arm.

Group II: Baking Soda, then Urocit-K Experimental Treatment 2 Interventions

After being off Urocit-K for two weeks, participants will collect two 24-hour urine tests to document hypocitraturia or low urine pH for calcium oxalate or uric acid stone formers, respectively. Participants will take Baking Soda dissolved in up to 250 mL of water ½ teaspoon (29.5 mEq) in AM and ½ Teaspoon (29.5 mEq) in PM for four weeks. During the last two days of the four-week drug period, two 24-hour urine collections will be obtained, and the participants will enter another washout period of two weeks before switching over to Urocit-K 30 mEq AM and 30 mEq PM for four weeks. During the last two days of this study arm, two 24-hour urine collections will be obtained. A basic metabolic panel blood test will be obtained at the end of the study arm.

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, Irvine

Lead Sponsor

Trials

580

Recruited

4,943,000+

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 involving 34 healthy volunteers, potassium sodium hydrogen citrate (PSHC) was found to significantly increase urine pH levels compared to sodium bicarbonate (NaHCO3), indicating that PSHC is more effective for urinary alkalization.

The study also revealed a natural circadian rhythm in urine pH, with both PSHC and NaHCO3 elevating urine pH levels without disrupting this rhythm, suggesting that PSHC can be used effectively without adverse effects on the body's natural processes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison potassium sodium hydrogen citrate with sodium bicarbonate in urine alkalization: a prospective crossover-controlled trial. Xue, W., Cheng, J., Zhao, J., et al.[2023]

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]

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 114 patients with chronic kidney disease (CKD) or end-stage renal disease (ESRD), a single 30g dose of sodium polystyrene sulfonate (SPS) significantly reduced serum potassium levels by a median of 0.8 mEq/L within 24 hours, indicating its efficacy in treating hyperkalemia.

While SPS was effective in lowering potassium, gastrointestinal side effects were reported in 5% of patients, raising concerns about potential risks associated with its use in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single-dose sodium polystyrene sulfonate for hyperkalemia in chronic kidney disease or end-stage renal disease. Hunt, TV., DeMott, JM., Ackerbauer, KA., et al.[2023]

Adding Splenda to potassium citrate (KCit) significantly improved the taste of the supplement, making it more palatable for patients, with a taste score increase of 2.5 points (P=0.02).

The addition of Splenda did not change the beneficial effects of KCit on 24-hour urine parameters related to kidney stone risk, ensuring that the treatment remains effective while enhancing compliance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Splenda® improves tolerance of oral potassium citrate supplementation for prevention of stone formation: results of a randomized double-blind trial. Mechlin, C., Kalorin, C., Asplin, J., et al.[2016]

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. Netherlands pubmed.ncbi.nlm.nih.gov

Comparison potassium sodium hydrogen citrate with sodium bicarbonate in urine alkalization: a prospective crossover-controlled trial. [2023]

3. Italy pubmed.ncbi.nlm.nih.gov

Sevelamer worsens metabolic acidosis in hemodialysis patients. [2015]

4. 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]

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

Sodium bicarbonate therapy in patients with metabolic acidosis. [2023]

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

Single-dose sodium polystyrene sulfonate for hyperkalemia in chronic kidney disease or end-stage renal disease. [2023]

7. Germany pubmed.ncbi.nlm.nih.gov

Sevelamer carbonate increases serum bicarbonate in pediatric dialysis patients. [2021]

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

Acetazolamide-induced renal calculi. [2019]

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

The Impact of Alternative Alkalinizing Agents on 24-Hour Urine Parameters. [2022]

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

Splenda® improves tolerance of oral potassium citrate supplementation for prevention of stone formation: results of a randomized double-blind trial. [2016]

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

Sodium Bicarbonate Prescription and Extracellular Volume Increase: Real-world Data Results from the AlcalUN Study. [2022]