Hydroxycitrate: A Novel Therapy for Calcium Phosphate Urinary Stones
- Conditions
- Calcium Phosphate Kidney Stones
- Interventions
- Dietary Supplement: OHCit- low doseDrug: PlaceboDietary Supplement: OHCit- standard dose
- Registration Number
- NCT06003348
- Lead Sponsor
- University of Texas Southwestern Medical Center
- Brief Summary
This study tests whether hydroxycitrate, a molecule closely related to citrate, can reduce calcium phosphate stone recurrence.
- Detailed 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 (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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 25
- Calcium Phosphate stone formers
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Super CitriMax; OHCit-low dose OHCit- low dose Super CitriMax 7 mEq 2 tabs, twice daily And Placebo 1 tab, twice daily Total Daily Dose: OHCit 28 mEq/d Placebo Placebo Placebo 3 tablets twice daily Total Daily Dose: None Super CitriMax; OHCit-standard dose OHCit- standard dose Super CitriMax 7 mEq 3 tabs, twice daily Total Daily Dose: OHCit 42 mEq/d Potassium Citrate (Urocit®-K) Potassium Citrate Potassium Citrate KCit 10 mEq 2 tabs, twice daily and Placebo 1 tab, twice daily Total Daily Dose: Citrate 40 mEq/d
- Primary Outcome Measures
Name Time Method Formation product (FP) for Calcium Phosphate After 1 week of treatment 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.
- Secondary Outcome Measures
Name Time Method Calcium Phosphate supersaturation After 1 week of treatment Supersaturation of calcium phosphate will be assessed by Joint Expert Speciation System (JESS).
Crystal growth of Calcium Phosphate After 1 week of treatment 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.
Trial Locations
- Locations (1)
UT Southwestern Medical Center
🇺🇸Dallas, Texas, United States