Hydroxycitrate: A Novel Therapy for Calcium Phosphate Urinary Stones

Sponsor

University of Texas Southwestern Medical Center (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT06003348

Collaborator

(none)

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Calcium Phosphate Kidney Stones	Dietary Supplement: OHCit- standard dose Drug: Potassium Citrate Drug: Placebo Dietary Supplement: OHCit- low dose	Phase 4

Detailed Description

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, KCit, or Super CitriMax. Study tablets will be prepared by a compounding pharmacy, with placebo tablets similar in appearance and size to the active medication tablets.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

25 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

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, OHCit low dose, OHCit standard dose, or Citrate. Randomization will be stratified based on sex, concomitant thiazide use, and concomitant alkali use.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, OHCit low dose, OHCit standard dose, or Citrate. Randomization will be stratified based on sex, concomitant thiazide use, and concomitant alkali use.

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Prevention

Official Title:

Hydroxycitrate: A Novel Therapy for Calcium Phosphate Urinary Stones

Anticipated Study Start Date :

Sep 1, 2023

Anticipated Primary Completion Date :

May 31, 2028

Anticipated Study Completion Date :

Aug 31, 2028

Arms and Interventions

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
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 Citramax
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 Citramax
Placebo Comparator: Placebo Placebo 3 tablets twice daily Total Daily Dose: None	Drug: Placebo Placebo

Outcome Measures

Primary Outcome Measures

Formation product for Calcium Phosphate [After 1 week of treatment]
FP is obtained by adding increasing amounts of CaCl2 to a series of urine aliquots maintained at constant pH for 2 hours, and is identified by the point at which CaP precipitates as detected by an absorbance microplate reader. Calculated supersaturation using [Ca] and [P] at that point represents FP.

Secondary Outcome Measures

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 [Ca]×[P] after seeding signifies crystal growth, while a [Ca]×[P] increment represents crystal dissolution.
Calcium Phosphate supersaturation [Supersaturation of calcium phosphate will be assessed by JESS.]
After 1 week of treatment

Eligibility Criteria

Criteria

Ages Eligible for Study:

21 Years to 99 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

CaP stone formers

Exclusion Criteria:

History of recurrent urinary tract infections
Chronic diarrhea
eGFR < 45 ml/min/1.73 m2
History of primary hyperparathyroidism
Hypokalemia
Hyperkalemia
Pregnancy

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

University of Texas Southwestern Medical Center

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Naim Maalouf, Professor, Internal Medicine, University of Texas Southwestern Medical Center

ClinicalTrials.gov Identifier:

NCT06003348

Other Study ID Numbers:

2023-0339

First Posted:

Aug 21, 2023

Last Update Posted:

Aug 21, 2023

Last Verified:

Aug 1, 2023

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Product Manufactured in and Exported from the U.S.:

Yes

Keywords provided by Naim Maalouf, Professor, Internal Medicine, University of Texas Southwestern Medical Center

Additional relevant MeSH terms:

Study Results

No Results Posted as of Aug 21, 2023