Hydroxycitrate for Kidney Stones

Overseen by Naim M Maalouf, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 4

Recruiting

Sponsor: University of Texas Southwestern Medical Center

Disqualifiers: Recurrent UTIs, Chronic diarrhea, eGFR < 45, others

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial tests whether hydroxycitrate can reduce the recurrence of kidney stones in patients who frequently get them. It compares hydroxycitrate to potassium citrate. The treatment works by preventing the formation of crystals that cause kidney stones. Hydroxycitrate is a derivative of citric acid and has shown the ability to inhibit the formation of calcium oxalate crystals in vitro.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications.

What data supports the effectiveness of the drug Hydroxycitrate for treating kidney stones?

Research shows that potassium citrate, a component of Hydroxycitrate, is effective in preventing kidney stones by increasing urinary citrate and pH levels, which reduces stone formation. ^{1 2 3 4 5}

Is Hydroxycitrate safe for humans?

Potassium citrate, a compound similar to Hydroxycitrate, is generally considered safe when used at therapeutic doses. It does not cause significant changes in blood chemistry, except for mild and temporary metabolic alkalosis (a condition where the body becomes too alkaline). ^{1 2 5 6 7}

How does the drug Hydroxycitrate work for kidney stones?

Hydroxycitrate, derived from Garcinia cambogia, is unique because it can dissolve calcium oxalate crystals, which are a common component of kidney stones. This makes it a potentially effective treatment for preventing and removing kidney stones, unlike other treatments that may not directly dissolve the stones. ^{8 9 10 11 12}

Research Team

Naim M Maalouf, MD

Principal Investigator

University of Texas Southwestern Medical Center

Eligibility Criteria

This trial is for people who form calcium phosphate kidney stones. It's not suitable for pregnant individuals, those with low potassium levels, frequent urinary infections, chronic diarrhea, poor kidney function (eGFR < 45), or a history of overactive parathyroid glands.

Inclusion Criteria

I form calcium phosphate kidney stones.

Exclusion Criteria

I have had multiple urinary tract infections.

Pregnancy

Low levels of potassium in your blood.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo four randomized phases: Placebo, Super CitriMax (OHCit) low dose, OHCit standard dose, or Potassium Citrate, each lasting 1 week with a 1-week washout period between phases.

4 weeks

Weekly visits for medication administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• OHCit- low dose (Dietary Supplement)
• OHCit- standard dose (Dietary Supplement)
• Placebo (Drug)
• Potassium Citrate (Drug)

Trial Overview The study is testing hydroxycitrate (OHCit) in two different doses to see if it can prevent new kidney stones from forming. Participants will also receive either Potassium Citrate or a placebo as part of the treatment comparison.

Participant Groups

Group I: Super CitriMax; OHCit-standard dose Experimental Treatment 1 Intervention

Super CitriMax 7 mEq 3 tabs, twice daily Total Daily Dose: OHCit 42 mEq/d

Group II: Super CitriMax; OHCit-low dose Experimental Treatment 1 Intervention

Super CitriMax 7 mEq 2 tabs, twice daily And Placebo 1 tab, twice daily Total Daily Dose: OHCit 28 mEq/d

Group III: Potassium Citrate (Urocit®-K) Active Control 1 Intervention

Potassium Citrate KCit 10 mEq 2 tabs, twice daily and Placebo 1 tab, twice daily Total Daily Dose: Citrate 40 mEq/d

Group IV: Placebo Placebo Group 1 Intervention

Placebo 3 tablets twice daily Total Daily Dose: None

Who Is Running the Clinical Trial?

University of Texas Southwestern Medical Center

Lead Sponsor

Trials

1,102

Recruited

1,077,000+

Daniel K. Podolsky

University of Texas Southwestern Medical Center

Chief Executive Officer since 2008

MD from Harvard Medical School

Robert L. Bass

University of Texas Southwestern Medical Center

Chief Medical Officer since 2019

MD from University of Texas Southwestern Medical School

Findings from Research

In a study of 176 children aged 5 to 18 with kidney stones, Polycitra-K was found to significantly reduce the occurrence of bladder stones compared to Bicitra, with 18.2% of Polycitra-K patients developing bladder stones versus 33% in the Bicitra group (p = 0.025).

Polycitra-K also led to a higher rate of stone passage, with 65.9% of patients in the Polycitra-K group successfully passing their stones compared to 40.9% in the Bicitra group, indicating its effectiveness in treating kidney stones through urine alkalization.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Polycitra-K and Bicitra in the Treatment of Pediatric Nephrolithiasis: A Double-Blind Randomized Trial. Razavi, MR., Vahedian, M., Motharinejad, F., et al.[2022]

K-CITEK, a new potassium-citrate regimen, was found to be equally effective as UROCIT-K in preventing kidney stones, based on a study of 104 patients.

Both treatments showed no significant differences in urinary citrate levels, stone burden, or the frequency of kidney stone events, indicating that K-CITEK is a viable alternative to UROCIT-K.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[A COMPARISON BETWEEN TWO POTASSIUM CITRATE REGIMENS FOR THE TREATMENT OF NEPHROLITHIASIS]. Drori, T., Abu-Ghanem, Y., Kleinmann, N., et al.[2020]

Potassium citrate therapy (60 mEq/day) significantly increased urinary pH and reduced urinary calcium levels in patients with uric acid stones, suggesting it may help prevent calcium nephrolithiasis complications.

Both potassium and sodium citrate effectively raised urinary pH to prevent uric acid stone formation, but potassium citrate showed additional benefits by lowering urinary calcium and enhancing the prevention of calcium oxalate precipitation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Contrasting effects of potassium citrate and sodium citrate therapies on urinary chemistries and crystallization of stone-forming salts. Sakhaee, K., Nicar, M., Hill, K., et al.[2022]

In a study involving five calcium oxalate stone formers, the ingestion of minimum doses of potassium citrate significantly increased citraturia and crystallization inhibitory capacity in urine samples.

The most effective timing for taking potassium citrate was after dinner, suggesting that this method could help reduce the risk of kidney stone formation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chronopharmacological studies on potassium citrate treatment of oxalocalcic urolithiasis. Grases, F., Conte, A., March, JG., et al.[2019]

Potassium citrate therapy significantly reduces the formation of kidney stones in patients, with a decrease in stone passage rates from 5.14-7.41 stones per patient per year to just 0.66-1.33 stones during treatment, achieving remission in 75.0-91.7% of patients.

The treatment effectively increases urinary citrate levels and pH, lowers calcium oxalate saturation, and decreases the likelihood of calcium oxalate nucleation, demonstrating its efficacy in preventing new stone formation across various patient groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Physiological and physiochemical correction and prevention of calcium stone formation by potassium citrate therapy. Pak, CY., Sakhaee, K., Fuller, CJ.[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]

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]

(-)-Hydroxycitric acid (HCA) from Garcinia fruit rinds effectively inhibits ATP citrate lyase, an enzyme crucial for converting citrate into acetyl-CoA, thereby limiting fatty acid synthesis and potentially aiding in weight loss.

While extensive animal studies support (-)-HCA's ability to suppress food intake and promote weight loss, clinical studies have shown mixed results, indicating a need for further research to clarify its efficacy in humans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemistry and biochemistry of (-)-hydroxycitric acid from Garcinia. Jena, BS., Jayaprakasha, GK., Singh, RP., et al.[2022]

(-)-Hydroxycitric acid (HCA) from Garcinia cambogia has been shown to inhibit fat synthesis and reduce food intake, with a primary mechanism of action involving the inhibition of the enzyme ATP-citrate lyase, which is crucial for fat and cholesterol production.

Safety studies indicate that HCA-SX, a more bioavailable form of HCA, is unlikely to cause reproductive or developmental effects, and human trials with doses up to 2800 mg/day reported no adverse effects, suggesting it is safe for consumption.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety assessment of (-)-hydroxycitric acid and Super CitriMax, a novel calcium/potassium salt. Soni, MG., Burdock, GA., Preuss, HG., et al.[2012]

Garcinia cambogia extract, particularly its component hydroxycitric acid (HCA), effectively dissolves calcium oxalate kidney stones in a Drosophila model, indicating its potential as a treatment for kidney stone disease.

The study demonstrated that GCE not only prevents the formation of calcium oxalate stones but also aids in their removal, suggesting that it could be a promising clinical option for patients suffering from nephrolithiasis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical-grade Garcinia cambogia extract dissolves calcium oxalate crystals in Drosophila kidney stone models. Fan, QX., Gong, SQ., Hong, XZ., et al.[2021]

In a 12-week study involving 44 participants, Garcinia cambogia extract significantly reduced visceral, subcutaneous, and total fat areas compared to a placebo, indicating its efficacy in targeting abdominal fat accumulation.

The study found no severe adverse effects from Garcinia cambogia, and there was no rebound effect in fat accumulation after the treatment period, suggesting it may be a safe option for managing obesity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of garcinia cambogia (Hydroxycitric Acid) on visceral fat accumulation: a double-blind, randomized, placebo-controlled trial. Hayamizu, K., Ishii, Y., Kaneko, I., et al.[2022]

A study on the teratogenic potential of HCA-SX, a calcium/potassium salt of hydroxycitric acid, found no evidence of maternal toxicity or fetal abnormalities in Sprague-Dawley rats at dietary exposure levels of 1000, 3000, and 10,000 ppm.

Despite a slight reduction in maternal weight gain at the highest dose, the study concluded that HCA-SX is not teratogenic, indicating it may be safe for use during pregnancy at these tested levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of a Novel Calcium/Potassium Saltof (-)-Hydroxycitric Acid (HCA-SX): II.Developmental Toxicity Study in Rats. Deshmukh, NS., Bagchi, M., Yasmin, T., et al.[2009]

References

1. Iran pubmed.ncbi.nlm.nih.gov

Effect of Polycitra-K and Bicitra in the Treatment of Pediatric Nephrolithiasis: A Double-Blind Randomized Trial. [2022]

2. Israel pubmed.ncbi.nlm.nih.gov

[A COMPARISON BETWEEN TWO POTASSIUM CITRATE REGIMENS FOR THE TREATMENT OF NEPHROLITHIASIS]. [2020]

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

Contrasting effects of potassium citrate and sodium citrate therapies on urinary chemistries and crystallization of stone-forming salts. [2022]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Chronopharmacological studies on potassium citrate treatment of oxalocalcic urolithiasis. [2019]

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

Physiological and physiochemical correction and prevention of calcium stone formation by potassium citrate therapy. [2013]

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

Augmentation of renal citrate excretion by oral potassium citrate administration: time course, dose frequency schedule, and dose-response relationship. [2019]

7. Poland pubmed.ncbi.nlm.nih.gov

[Therapeutic use of potassium citrate]. [2022]

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

Chemistry and biochemistry of (-)-hydroxycitric acid from Garcinia. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Safety assessment of (-)-hydroxycitric acid and Super CitriMax, a novel calcium/potassium salt. [2012]

10. Italy pubmed.ncbi.nlm.nih.gov

Clinical-grade Garcinia cambogia extract dissolves calcium oxalate crystals in Drosophila kidney stone models. [2021]

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

Effects of garcinia cambogia (Hydroxycitric Acid) on visceral fat accumulation: a double-blind, randomized, placebo-controlled trial. [2022]

12. England pubmed.ncbi.nlm.nih.gov

Safety of a Novel Calcium/Potassium Saltof (-)-Hydroxycitric Acid (HCA-SX): II.Developmental Toxicity Study in Rats. [2009]