Hydroxycitrate: A Novel Therapy for Calcium Phosphate Urinary Stones

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

Study Overview

• Status: Recruiting
• Conditions: Calcium Phosphate Kidney Stones
• Intervention / Treatment: Drug: Placebo; Drug: Potassium Citrate; Dietary supplement: OHCit- standard dose; Dietary supplement: OHCit- low dose

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.

• Study Type: Interventional
• Enrollment (Estimated): 25
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: NAIM M MAALOUF, MD; Phone Number: 214/648-2954; Email: naim.maalouf@utsouthwestern.edu
• Study Contact Backup: Name: Miranda King; Phone Number: 2146482117; Email: Miranda.King@utsouthwestern.edu

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75390-8885
      • Recruiting
      • UT Southwestern Medical Center
      • Contact: Naim M Maalouf, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Potassium Citrate (Urocit®-K); 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; 10 mEq Extended-release tablets for oral use; Other Names: Urocit®-K
Placebo Comparator: Placebo; Placebo 3 tablets twice daily Total Daily Dose: None	Drug: Placebo; Placebo
Experimental: Super CitriMax; OHCit-standard dose; Super CitriMax 7 mEq 3 tabs, twice daily Total Daily Dose: OHCit 42 mEq/d	Dietary supplement: OHCit- standard dose; Hydroxycitrate Over-the-counter supplement, not FDA approved or regulated.; Other Names: Super Citrimax
Experimental: Super CitriMax; OHCit-low dose; 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; Hydroxycitrate Over-the-counter supplement, not FDA approved or regulated.; Other Names: Super Citrimax

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Texas Southwestern Medical Center
• Investigators: Principal Investigator: NAIM M MAALOUF, University of Texas Southwestern Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): December 13, 2023
• Primary Completion (Estimated): May 31, 2028
• Study Completion (Estimated): August 31, 2028

Study Registration Dates

• First Submitted: August 14, 2023
• First Submitted That Met QC Criteria: August 14, 2023
• First Posted (Actual): August 21, 2023

Study Record Updates

• Last Update Posted (Actual): June 2, 2026
• Last Update Submitted That Met QC Criteria: June 1, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Urolithiasis; Citrate; Calcium phosphate; Acid-base
• Additional Relevant MeSH Terms: Urogenital Diseases; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urolithiasis; Organic Chemicals; Acids, Acyclic; Carboxylic Acids; Citrates; Tricarboxylic Acids; Citric Acid; Potassium Citrate; Super Citrimax
• Other Study ID Numbers: 2023-0339

Drug and device information, study documents

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