Pharmacological Therapy for Calcium Phosphate Urolithiasis

Study ID
STU 032012-058

Cancer Related
No

Healthy Volunteers
No

Study Sites

Contact
Ashlei Johnson-Wilder
214-648-0394
ashlei.johnson@utsouthwestern.edu

Principal Investigator
Naim Maalouf

Summary

aim 1:
Study protocol: in this double-blind, placebo-controlled, crossover study, each subject will undergo 3 phases, the order of which will be randomized by a simple randomization scheme. The 3 phases will be Placebo (PBo), Citric acid (Cita), and Potassium Citrate (KCit). each phase will be 1 week in duration, during which subjects will take assigned study medications. a 1-week washout period is imposed between phases. During the first 2 days of each phase, subjects will be instructed to adhere to a diet at home with a daily composition of 800 mg calcium, 100 meq sodium, 800 mg phosphorus, 50 meq potassium and 2 liters of total fluids daily. on the last 5 days of each phase, subjects will be kept on a constant metabolic diet of the same composition provided by the Clinical and Translational Research Center (CTRC). During the final two study days (days 6-7), subjects will be admitted to the CTRC where a 24-hr urine will be collected on day 6 under mineral oil to measure urine chemistries (stone risk factors) and acid-base parameters, and on day 7 for crystallization studies. Fasting blood will be obtained at the end of each urine collection.

aim 2:
Study protocol: in this double-blind, placebo-controlled crossover study, each hypercalciuric CaP stone former will undergo 3 phases, the order of which will be randomized by a simple randomization scheme. The 3 phases will be indapamide+KCl+PBo, indapamide+KCl+Cita, and indapamide+KCit+PBo. The dose of indapamide will be fixed at 1.25 mg/day in each subject, the amount of potassium provided as KCit or KCl will be kept constant at 20 meq BiD, and the amount of Citrate provided either as KCit or Cita will be 20 meq BiD. This will allow for direct assessment of effects of KCl vs. KCl+Cita vs. KCit. Subjects will be studied in the same experimental protocol described in aim 1.

Participant Eligibility

Aim 1:
Hypocitraturic CaP stone formers with elevated urine pH will be >21 years, of either gender, any race and ethnicity. Hypocitraturia will be defined as 24-hr urine citrate < 320 mg/d and elevated pH as 24-hr urine pH above 6.406, 7 in the absence of urinary tract infection. CaP stone disease will be defined based on most recent available stone composition with CaP constituting over 70% of overall stone components.

Aim 2:
Hypercalciuric CaP stone formers with elevated urine pH will be >21 years, of either gender, any race and ethnicity. Hypercalciuria will be defined as 24-hr urine calc ium > 250 mg/d in women and > 300 mg/d in men prior to indapamide use, and high pH as >6.40 in the absence of urinary tract infection. CaP stone disease will be defined based on most recent available stone composition with CaP constituting over 70% of overall stone components. Subjects will be included irrespective of urinary citrate