Treatment for Calcium Phosphate Kidney Stone Disease

Pharmacological Therapy for Calcium Phosphate Urolithiasis

The investigators will examine in two studies whether citric acid or potassium citrate can reduce calcium phosphate saturation in urine of Calcium Phosphate stone formers.

Study Overview

• Status: Completed
• Conditions: Calcium Phosphate Kidney Stones
• Intervention / Treatment: Dietary supplement: Placebo; Dietary supplement: Citric Acid; Dietary supplement: Potassium Citrate

Detailed Description

We will examine in two short-term placebo-controlled cross-over metabolic studies whether citric acid or potassium citrate can reduce calcium phosphate saturation in urine of CaP stone formers.

The first study will be conducted in hypocitraturic CaP stone formers without hypercalciuria, and will compare the effects of potassium citrate, citric acid and placebo.

The second study will be conducted in hypercalciuric CaP stone formers on a thiazide diuretic who require potassium supplementation, and will compare the effects of potassium chloride alone, potassium chloride + citric acid, and potassium citrate alone. Physicochemical assays will be applied in addition to computer-based stone risk prediction programs to assess risk of stone recurrence.

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75390-8885
      • UT Southwestern Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Aim 1

• Hypocitraturic CaP stone formers
• urine citrate <320mg/d
• elevated pH as 24-hr urine pH above 6.40
• >21 years

Aim 2

• Hypercalciuric CaP stone formers
• 24hr urine calcium >250mg/d in women and >300mg/d in men prior to indapamide use
• high pH as >6.40 in the absence of urinary tract infection
• >21 years

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Placebo, then Citric Acid, then Potassium Citrate; Participants will receive at random, First intervention (1 week), then experience a washout period (1 week) and then receive Second Intervention (1 week) followed by another washout period of 1 week to finally receive the Third Intervention (1 week)	Dietary supplement: Placebo; 3 tablets twice daily of matching placebo during the placebo phase.; Dietary supplement: Citric Acid; 3, 10 mEq tablets of H3Cit twice daily during the H3Cit phase (60 mEq H3Cit per day); Dietary supplement: Potassium Citrate; 2, 10 mEq K3Cit tablets and 1 placebo tablet twice daily during the K3Cit phase (40 mEq K3Cit per day)
Experimental: Placebo, then Potassium Citrate, then Citric Acid; Participants will receive at random, First intervention (1 week), then experience a washout period (1 week) and then receive Second Intervention (1 week) followed by another washout period of 1 week to finally receive the Third Intervention (1 week)	Dietary supplement: Placebo; 3 tablets twice daily of matching placebo during the placebo phase.; Dietary supplement: Citric Acid; 3, 10 mEq tablets of H3Cit twice daily during the H3Cit phase (60 mEq H3Cit per day); Dietary supplement: Potassium Citrate; 2, 10 mEq K3Cit tablets and 1 placebo tablet twice daily during the K3Cit phase (40 mEq K3Cit per day)
Experimental: Potassium Citrate, then Placebo, then Citric Acid; Participants will receive at random, First intervention (1 week), then experience a washout period (1 week) and then receive Second Intervention (1 week) followed by another washout period of 1 week to finally receive the Third Intervention (1 week)	Dietary supplement: Placebo; 3 tablets twice daily of matching placebo during the placebo phase.; Dietary supplement: Citric Acid; 3, 10 mEq tablets of H3Cit twice daily during the H3Cit phase (60 mEq H3Cit per day); Dietary supplement: Potassium Citrate; 2, 10 mEq K3Cit tablets and 1 placebo tablet twice daily during the K3Cit phase (40 mEq K3Cit per day)
Experimental: Potassium Citrate, then Citric Acid, then Placebo; Participants will receive at random, First intervention (1 week), then experience a washout period (1 week) and then receive Second Intervention (1 week) followed by another washout period of 1 week to finally receive the Third Intervention (1 week)	Dietary supplement: Placebo; 3 tablets twice daily of matching placebo during the placebo phase.; Dietary supplement: Citric Acid; 3, 10 mEq tablets of H3Cit twice daily during the H3Cit phase (60 mEq H3Cit per day); Dietary supplement: Potassium Citrate; 2, 10 mEq K3Cit tablets and 1 placebo tablet twice daily during the K3Cit phase (40 mEq K3Cit per day)
Experimental: Citric Acid, then Potassium Citrate, then Placebo; Participants will receive at random, First intervention (1 week), then experience a washout period (1 week) and then receive Second Intervention (1 week) followed by another washout period of 1 week to finally receive the Third Intervention (1 week)	Dietary supplement: Placebo; 3 tablets twice daily of matching placebo during the placebo phase.; Dietary supplement: Citric Acid; 3, 10 mEq tablets of H3Cit twice daily during the H3Cit phase (60 mEq H3Cit per day); Dietary supplement: Potassium Citrate; 2, 10 mEq K3Cit tablets and 1 placebo tablet twice daily during the K3Cit phase (40 mEq K3Cit per day)
Experimental: Citric Acid, then Placebo, then Potassium Citrate; Participants will receive at random, First intervention (1 week), then experience a washout period (1 week) and then receive Second Intervention (1 week) followed by another washout period of 1 week to finally receive the Third Intervention (1 week)	Dietary supplement: Placebo; 3 tablets twice daily of matching placebo during the placebo phase.; Dietary supplement: Citric Acid; 3, 10 mEq tablets of H3Cit twice daily during the H3Cit phase (60 mEq H3Cit per day); Dietary supplement: Potassium Citrate; 2, 10 mEq K3Cit tablets and 1 placebo tablet twice daily during the K3Cit phase (40 mEq K3Cit per day)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Urinary Calcium Phosphate Saturation	This variable represents a ratio of the calcium phosphate saturation in a given urine sample to the calcium phosphate saturation at the point of precipitation and hence this measure has no units.	2 weeks

Collaborators and Investigators

• Sponsor: University of Texas Southwestern Medical Center
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Investigators: Principal Investigator: Naim M Maalouf, MD, UT Southwestern Medical Center

Publications and helpful links

General Publications

• Doizi S, Poindexter JR, Pearle MS, Blanco F, Moe OW, Sakhaee K, Maalouf NM. Impact of Potassium Citrate vs Citric Acid on Urinary Stone Risk in Calcium Phosphate Stone Formers. J Urol. 2018 Dec;200(6):1278-1284. doi: 10.1016/j.juro.2018.07.039. Epub 2018 Jul 20.

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2012
• Primary Completion (Actual): February 16, 2023
• Study Completion (Actual): February 16, 2023

Study Registration Dates

• First Submitted: December 14, 2012
• First Submitted That Met QC Criteria: December 18, 2012
• First Posted (Estimated): December 21, 2012

Study Record Updates

• Last Update Posted (Actual): April 4, 2024
• Last Update Submitted That Met QC Criteria: March 7, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: kidney stones; urolithiasis; calcium phosphate; hypercalciuria
• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Pathological Conditions, Anatomical; Urolithiasis; Urinary Calculi; Calculi; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Calculi; Nephrolithiasis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Natriuretic Agents; Diuretics; Respiratory System Agents; Anticoagulants; Chelating Agents; Sequestering Agents; Expectorants; Calcium Chelating Agents; Citric Acid; Sodium Citrate; Potassium Citrate
• Other Study ID Numbers: 032012-058; R21DK097476-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No