Hydroxycitrate for Kidney Stones

Overseen By Naim M Maalouf, MD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: University of Texas Southwestern Medical Center

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

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

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

25 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if hydroxycitrate can reduce the recurrence of calcium phosphate kidney stones. Researchers compare hydroxycitrate (OHCit) at low and standard doses, potassium citrate, and a placebo to identify the most effective prevention method. Individuals who have formed calcium phosphate kidney stones and do not frequently experience urinary tract infections may be suitable for this study. As a Phase 4 trial, this research explores how an already FDA-approved and effective treatment can benefit more patients.

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 is the safety track record for these treatments?

Research has shown that hydroxycitrate (OHCit) is generally safe for people. In several studies, participants took up to 2800 mg of hydroxycitrate daily without experiencing related side effects. These findings suggest that hydroxycitrate is safe for humans at these doses. While these results are encouraging, monitoring for any side effects during clinical trials remains important. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Most treatments for kidney stones, like Potassium Citrate, work by increasing the levels of citrate in the urine to prevent stone formation. But Hydroxycitrate (OHCit) offers a fresh approach. It not only increases citrate levels but also directly dissolves calcium deposits, which are the building blocks of most kidney stones. Researchers are excited about OHCit because this dual action could potentially lead to more effective prevention and even reduction of existing stones. Additionally, OHCit is derived from a natural source, making it an attractive option for those seeking treatments with natural origins.

What evidence suggests that this trial's treatments could be effective for kidney stones?

Research has shown that hydroxycitrate, similar to citrate, can help prevent kidney stones. Studies have found that it stops calcium crystals from forming, a main cause of kidney stones. One study discovered that hydroxycitrate improved key blood and urine indicators related to stone formation and reduced kidney damage caused by these crystals. Additionally, hydroxycitrate has been observed to lower the risk of mineral build-up in kidney tissues. This trial will evaluate different doses of hydroxycitrate, with some participants receiving a low dose and others a standard dose, to assess its effectiveness in reducing the recurrence of kidney stones. ^{5 6 7 8 9}

Who Is on the Research Team?

Naim M Maalouf, MD

Principal Investigator

University of Texas Southwestern Medical Center

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• OHCit- low dose
• OHCit- standard dose
• Placebo
• Potassium Citrate

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.

How Is the Trial Designed?

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

OHCit- low dose is already approved in United States, European Union for the following indications:

Approved in United States as Hydroxycitric Acid for:

• Weight loss
• Exercise performance

Approved in European Union as Hydroxycitric Acid for:

• Weight loss
• Exercise performance

Who Is Running the Clinical Trial?

University of Texas Southwestern Medical Center

Lead Sponsor

Trials

1,102

Recruited

1,077,000+

Published Research Related to This 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 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]

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]

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]

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]

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 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]

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]

(-)-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]

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]

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]

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