Calcium Phosphate Kidney Stones
Conditions
Keywords
Urolithiasis, Calcium phosphate, Citrate, Acid-base
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.
Interventions
DIETARY_SUPPLEMENTOHCit- standard dose
Hydroxycitrate Over-the-counter supplement, not FDA approved or regulated.
10 mEq Extended-release tablets for oral use
DRUGPlacebo
Placebo
DIETARY_SUPPLEMENTOHCit- low dose
Hydroxycitrate Over-the-counter supplement, not FDA approved or regulated.
Sponsors
University of Texas Southwestern Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention 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.
Eligibility
Sex/Gender
ALL
Age
21 Years to 99 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| Calcium Phosphate supersaturation | After 1 week of treatment | Supersaturation of calcium phosphate will be assessed by Joint Expert Speciation System (JESS). |
Countries
United States
Contacts
Primary ContactNAIM M MAALOUF, MD
Backup ContactMiranda King
Outcome results
None listed