Hydroxycitrate: A Novel Therapy for Calcium Phosphate Urinary Stones

Study Overview
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Brief Summary
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This study tests whether hydroxycitrate, a molecule closely related to citrate, can reduce calcium phosphate stone recurrence.

Detailed Description
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In this double-blind, placebo-controlled, randomized, crossover study, each participant will undergo 4 phases of study, with the order randomized by a blocked randomization scheme. The 4 phases will be Placebo, Super CitriMax (hydroxycitrate) OHCit low dose, OHCit standard dose, or Potassium Citrate. Randomization will be stratified based on sex, concomitant thiazide use, and concomitant alkali use. Each phase will be 1 week in duration, during which subjects will take assigned study medications. A minimum 1-week washout period will be imposed between phases. During the first 2 days of each phase, subjects will be instructed to adhere to a prescribed diet. On the last 5 days of each phase, subjects will be kept on a constant metabolic diet. Use of metabolic diet is essential to eliminate confounders that could occur from changes in dietary intake across phases. During the final two study days (days 6-7), two 24-hr urines will be collected for urine biochemistry and crystallization studies. Fasting blood will be obtained at the end of the last urine collection. Study Medications: Subjects will receive three tablets twice daily during each phase. These will consist of either placebo, Potassium Citrate (KCit), or Super CitriMax (OHCit). Study tablets will be prepared by a compounding pharmacy, with placebo tablets similar in appearance and size to the active medication tablets.

Official Title
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Hydroxycitrate: A Novel Therapy for Calcium Phosphate Urinary Stones

Conditions
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Calcium Phosphate Kidney Stones

Intervention / Treatment
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* Dietary Supplement: OHCit- standard dose
* Drug: Potassium Citrate
* Drug: Placebo
* Dietary Supplement: OHCit- low dose


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: - Calcium Phosphate stone formers Exclusion Criteria: History of recurrent urinary tract infections Chronic diarrhea Estimated Glomerular Filtration Rate (eGFR) < 45 ml/min/1.73 m2 History of primary hyperparathyroidism Hypokalemia Hyperkalemia Pregnancy

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: In this double-blind, placebo-controlled, randomized, crossover study, each participant will undergo 4 phases of study, with the order randomized by a blocked randomization scheme. The 4 phases will be Placebo, Super CitriMax (OHCit) low dose, Super CitriMax (OHCit) standard dose, or Potassium Citrate. Randomization will be stratified based on sex, concomitant thiazide use, and concomitant alkali use.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Potassium Citrate (Urocit®-K)<br>Potassium Citrate KCit 10 mEq 2 tabs, twice daily and Placebo 1 tab, twice daily Total Daily Dose: Citrate 40 mEq/d | Drug: Potassium Citrate<br>* 10 mEq Extended-release tablets for oral use<br>* Other names: Urocit®-K;|
| Experimental: Super CitriMax; OHCit-standard dose<br>Super CitriMax 7 mEq 3 tabs, twice daily Total Daily Dose: OHCit 42 mEq/d | Dietary Supplement: OHCit- standard dose<br>* Hydroxycitrate Over-the-counter supplement, not FDA approved or regulated.<br>* Other names: Super Citrimax;|
| Experimental: Super CitriMax; OHCit-low dose<br>Super CitriMax 7 mEq 2 tabs, twice daily And Placebo 1 tab, twice daily Total Daily Dose: OHCit 28 mEq/d | Dietary Supplement: OHCit- low dose<br>* Hydroxycitrate Over-the-counter supplement, not FDA approved or regulated.<br>* Other names: Super Citrimax;|
| Placebo Comparator: Placebo<br>Placebo 3 tablets twice daily Total Daily Dose: None | Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Formation product (FP) for Calcium Phosphate | FP is obtained by adding increasing amounts of Calcium Chloride (CaCl2) to a series of urine aliquots maintained at constant pH for 2 hours, and is identified by the point at which calcium phosphate (CaP) precipitates as detected by an absorbance microplate reader. Calculated supersaturation using [Calcium] and [Phosphate] at that point represents FP. | After 1 week of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Crystal growth of Calcium Phosphate | We will assess crystal growth (CG) of CaP after seeding urine with a small amount of brushite (0.25 mg/ml urine) and incubating at 37°C for 3 hours (representing steady state) under constant stirring. A decrement in [Calcium]×[Phosphate] after seeding signifies crystal growth, while a [Calcium]×[Phosphate] increment represents crystal dissolution. | After 1 week of treatment | 
| Calcium Phosphate supersaturation | Supersaturation of calcium phosphate will be assessed by Joint Expert Speciation System (JESS). | After 1 week of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Urolithiasis, Calcium phosphate, Citrate, Acid-base