Potassium Citrate for Kidney Disease

(BICARb Trial)

Recruiting at 2 trial locations

Overseen By Kimberly L Reidy, MD

Age: Any Age

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Albert Einstein College of Medicine

Must not be taking: Bisphosphonates, Denosumab, others

Disqualifiers: Hyperkalemia, Acid-base imbalance, others

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

Compensation: Varies

Number of Visits: 3

Duration: 6 months

103 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether potassium citrate can improve bone health in people with chronic kidney disease. Researchers aim to determine if it strengthens bones and how it affects skeletal health. Participants will take either potassium citrate or a placebo (a pill with no active ingredients) for six months. Those with chronic kidney disease who manage related health issues, such as maintaining specific vitamin D levels, might be suitable for this trial. As a Phase 2, Phase 3 trial, this research measures the treatment's effectiveness in an initial, smaller group and represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking advancements in treatment.

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 a potassium-lowering agent or certain bone-related medications like bisphosphonates or hormone replacement therapies. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that potassium citrate is usually safe for most people. One study found it helped prevent kidney stones without causing serious side effects. However, it can sometimes raise potassium levels in the blood, particularly in individuals with kidney problems, potentially leading to hyperkalemia, which means having too much potassium in the blood.

People with conditions like heart disease or diabetes should exercise caution when using potassium citrate. Some may experience minor side effects, such as an upset stomach. Participants should be aware of these possible issues. It is important to consult a healthcare provider about any concerns before considering joining a trial involving potassium citrate. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for kidney disease, which often include dietary changes and medications like ACE inhibitors or ARBs, potassium citrate offers a new approach by directly addressing the body's acid-base balance. This treatment is unique because it uses an extended-release tablet or an oral solution to provide consistent dosing throughout the day, which could potentially reduce the acid load on the kidneys. Researchers are excited about potassium citrate because it may help slow the progression of kidney disease by targeting a different mechanism compared to current options, offering hope for improved kidney function and patient outcomes.

What evidence suggests that potassium citrate might be an effective treatment for chronic kidney disease?

Research has shown that potassium citrate can help prevent certain kidney stones from forming. Studies indicate that people taking potassium citrate have a 70-75% chance of avoiding kidney stones within a year. In this trial, participants will receive either potassium citrate or a placebo. Although the study primarily focuses on bone health for those with chronic kidney disease, potassium citrate has been found to improve citrate levels in urine, potentially benefiting bone health. It also appears to increase magnesium in urine, which could support bone strength. These findings suggest that potassium citrate might improve bone quality and strength, but researchers are still gathering more direct evidence. ^{4 5 6 7 8}

Who Is on the Research Team?

Kimberly Reidy, MD

Principal Investigator

Albert Einstein College of Medicine

Are You a Good Fit for This Trial?

This trial is for adults and children over 5 with chronic kidney disease who have normal PTH, phosphorus, and vitamin D levels. Women must use contraception and not be pregnant or breastfeeding. Participants can't join if they have certain metabolic bone diseases, high potassium levels, heart risks on ECG, severe other illnesses affecting acid-base balance, a history of kidney stones or limb amputations.

Inclusion Criteria

Women of childbearing potential must be willing to use one form of effective contraception over the course of the study

My child's kidney function is moderately reduced but not severely.

I have had a menstrual period in the last month.

Exclusion Criteria

I have had a solid or liquid organ transplant.

I have had fractures in both my wrists and shins.

My potassium levels are high or I've had high potassium in the last 6 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Run-in Period

Participants take study pills for 4-6 weeks to ensure safety

4-6 weeks

Treatment

Participants take either potassium citrate or placebo for 6 months during the blinded portion of the study

6 months

3 visits (in-person) for blood, urine, and health/diet assessments; 2 visits (in-person) for advanced bone imaging

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• Potassium citrate

Trial Overview

The study tests if potassium citrate improves bone health in those with chronic kidney disease by comparing it to a placebo. Over 8 months, participants will take pills for safety checks then either the treatment or placebo for 6 months while undergoing blood tests, diet surveys, and advanced bone scans.

How Is the Trial Designed?

Group I: Potassium Citrate Experimental Treatment 2 Interventions

Potassium Citrate extended-release tablets 30 mEq twice daily. 1 mEq/kg/day divided into two doses for children to a maximum dose of 30 mEq twice daily. OR (for children who cannot take pills): Potassium citrate and citric acid for oral solution 1 mEq/kg/day divided into two doses to a maximum dose of 30 mEq twice daily

Group II: Placebo Placebo Group 1 Intervention

Placebo capsules identical to the active capsules.

Who Is Running the Clinical Trial?

Albert Einstein College of Medicine

Lead Sponsor

Trials

302

Recruited

11,690,000+

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

Collaborator

Trials

2,513

Recruited

4,366,000+

University of Utah

Collaborator

Trials

1,169

Recruited

1,623,000+

University of Pittsburgh Medical Center

Collaborator

Trials

78

Recruited

77,600+

Columbia University

Collaborator

Trials

1,529

Recruited

2,832,000+

Published Research Related to This Trial

In a study of 9 patients with incomplete distal renal tubular acidosis, oral potassium citrate therapy significantly increased urinary pH and citrate levels while decreasing urinary calcium, which helps prevent kidney stone formation.

Over a mean treatment period of 34 months, none of the patients developed new kidney stones, demonstrating the long-term efficacy of potassium citrate in managing calcium nephrolithiasis associated with this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prevention of recurrent calcium stone formation with potassium citrate therapy in patients with distal renal tubular acidosis. Preminger, GM., Sakhaee, K., Skurla, C., et al.[2022]

Potassium citrate is effective in preventing the formation and relapse of certain types of kidney stones, with a one-year remission rate of 70-75% in patients treated for stone disease.

It is generally safe when used at therapeutic doses, causing only mild transient metabolic alkalosis and no significant changes in blood biochemical parameters, while effectively reducing urine calcium and increasing oxalate calcium phosphate excretion.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Therapeutic use of potassium citrate]. Zmonarski, SC., Klinger, M., Puziewicz-Zmonarska, A., et al.[2022]

Potassium citrate therapy significantly reduced new stone formation in patients with mild to moderately severe stone disease, achieving a remission rate of 96% (from 0.52 to 0.02 stones per patient per year, p < 0.001).

In contrast, conservative measures or placebo trials only decreased new stone formation by 54% (from 0.54 to 0.25 stones per patient per year), indicating that potassium citrate provides a more effective treatment beyond standard conservative approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative efficacy of "specific" potassium citrate therapy versus conservative management in nephrolithiasis of mild to moderate severity. Preminger, GM., Harvey, JA., Pak, CY.[2019]

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]

In a study of 15 patients treated with granulated potassium citrate for one month, significant biochemical changes were observed, including improvements in serum potassium, creatinine, and urinary pH, citrate, and potassium levels.

The treatment was well tolerated, confirming that potassium citrate is an effective and user-friendly option for preventing oxalocalcium kidney stones.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Granulated potassium citrate in the prevention of calcium oxalate lithiasis]. Campoy Martínez, P., Arrabal Martín, M., Quintero Rodríguez, R., et al.[2013]

In a study of 8 pediatric patients with distal renal tubular acidosis (RTA), potassium citrate at a dosage of 4 mEq/kg/d effectively corrected most urinary abnormalities associated with nephrolithiasis, particularly reducing elevated urinary saturation for calcium oxalate.

The study found that while potassium citrate normalized several urinary ratios, the elevated urinary saturation for calcium phosphate could not be corrected, indicating that while potassium citrate is beneficial, it may not address all urinary issues in distal RTA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dosage of potassium citrate in the correction of urinary abnormalities in pediatric distal renal tubular acidosis patients. Domrongkitchaiporn, S., Khositseth, S., Stitchantrakul, W., et al.[2013]

ADV7103, a new prolonged-release formulation for treating distal renal tubular acidosis (dRTA), demonstrated good safety and tolerability over a 24-month study with only 9 mild gastrointestinal adverse events related to the treatment, and no discontinuations due to adverse effects.

The treatment effectively maintained normal plasma bicarbonate and potassium levels in 69-86% and 83-93% of patients, respectively, while achieving a high adherence rate of over 75% in 79% of participants and an impressive 89% improvement in quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, efficacy, and acceptability of ADV7103 during 24 months of treatment: an open-label study in pediatric and adult patients with distal renal tubular acidosis. Bertholet-Thomas, A., Guittet, C., Manso-Silván, MA., et al.[2021]

Potassium citrate is an effective treatment for managing various types of kidney stones, including calcium stones associated with renal tubular acidosis and hypocitraturic calcium oxalate nephrolithiasis.

It also helps in treating uric acid stones, demonstrating its broad utility in stone disease management, particularly for patients with specific underlying conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Citrate and renal calculi. Pak, CY.[2013]

In a study involving 43 participants (22 normal volunteers and 21 patients with kidney stones), a slow-release potassium citrate preparation effectively increased urinary citrate levels for up to 12 hours after a single dose, helping to maintain higher citrate levels throughout the day.

Potassium citrate at a dosage of 60 meq/day was able to restore normal urinary citrate levels in most patients with low citrate levels, which is beneficial for preventing kidney stone formation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Augmentation of renal citrate excretion by oral potassium citrate administration: time course, dose frequency schedule, and dose-response relationship. Pak, CY., Skurla, C., Brinkley, L., et al.[2019]

The 'K+ in CKD' study is a randomized, double-blind trial involving 399 patients with chronic kidney disease (CKD) to investigate the effects of potassium supplementation on kidney function over 2 years.

The study aims to determine if potassium supplementation can protect kidney function and improve cardiovascular outcomes, with safety measures in place to monitor for hyperkalemia during the trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rationale and Design of a Randomized Placebo-Controlled Clinical Trial Assessing the Renoprotective Effects of Potassium Supplementation in Chronic Kidney Disease. Gritter, M., Vogt, L., Yeung, SMH., et al.[2023]

Citations

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Efficacy and tolerability of potassium citrate sachet versus

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Impact of potassium citrate on urinary risk profile, glucose and ...

Treatment with potassium citrate was associated with a significantly higher mean change in urinary citrate (P = 0.010) and urinary magnesium (P = 0.020)

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clinicaltrials.gov

clinicaltrials.gov/study/NCT03007160

A Study on the Effection of Potassium Citrate Extended ...

This study takes "Rate of stone recurrence" as primary outcome measure, by random, blank control, and multicenter clinical trial design method, assess the ...

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withpower.com

withpower.com/trial/phase-2-and-3-kidney-diseases-6-2023-d17df

Potassium Citrate for Kidney Disease (BICARb Trial)

Potassium citrate is effective in preventing the formation and relapse of certain types of kidney stones, with a one-year remission rate of 70-75% in patients ...

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC5662332/

Safety of potassium-bearing citrate in patients with renal ...

The application of PSHC may increase the risk of hyperkalemia in patients undergoing renal transplantation. Physicians should keep a watchful ...

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mayoclinic.org

mayoclinic.org/drugs-supplements/potassium-citrate-oral-route/description/drg-20074773

Potassium citrate (oral route) - Side effects & dosage

Heart disease or; Kidney disease—Use with caution. May make these conditions worse. Adrenal problems or; Dehydration or; Diabetes mellitus ...

8.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC7769539/

Impact of potassium citrate on urinary risk profile, glucose ...

Treatment with potassium citrate was associated with a significantly higher mean change in urinary citrate (P = 0.010) and urinary magnesium (P ...