Effect of a High Citrate Beverage on Urine Chemistry in Urinary Stone Disease

NCT04697706 | Completed Early Phase 1 DMC

• 1 other identifier: 20-01153
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

This study will investigate the effect of a patented high citrate beverage on urine chemistry in patients with urinary stone disease (USD). It is a minimal risk study of an over-the-counter beverage called Moonstone, which is commercially available. This study is considered preparatory for the RO-1 and is not intended to produce a definitive outcome regarding kidney stones.

Conditions

Urinary Stone

Outcome Measures

Primary Outcomes (4)

• Urine citrate excretion

  In calcium stone formers, the effect of Moonstone on urine citrate excretion will be compared to that of water in a non-inferiority analysis.

  24 hours

• 24-hour urine volume

  The effects of Moonstone on 24-hour urine volume, calcium excretion and SS will be compared.

  24 hours

• 24-hour urine pH

  The effect of Moonstone on 24-hour urine pH will be compared to that of water in a non-inferiority analysis in both cystine and uric acid stone formers

  24 hours

• Increase in 24-hour urine citrate excretion

  A secondary outcome is an increase in 24-hour urine citrate excretion after Moonstone, compared with a period of water, in calcium stone-forming individuals.

  24 hours

Study Arms (2)

Study period "Water"

ACTIVE COMPARATOR

Participants will take in 1L of tap water per day plus ad lib, self-selected fluids.

Other: Water

Study period "Moonstone"

EXPERIMENTAL

Participants will take one packet of Moonstone powder reconstituted in 500 ml water, twice a day, to total 1 L per day (66 meq of potential alkali/day) plus ad lib fluids. Moonstone packets will be supplied by Dr. Arnie's, Inc.

Dietary Supplement: Moonstone

Interventions

Moonstone DIETARY_SUPPLEMENT

Participants will take one packet of Moonstone powder reconstituted in 500 ml water, twice a day, to total 1 L per day (66 meq of potential alkali/day) plus ad lib fluids. Moonstone packets will be supplied by Dr. Arnie's, Inc. Participants will follow their own self-chosen ad lib diets and complete a diet diary (Appendix) for days 6 and 7 in the first study period. On day 7, a 24-hour urine collection will be performed, and a 50-ml aliquot of urine will be sent to Litholink (Chicago, IL) via FedEx for analysis. Participants will then continue to the second study period and will use the diet diary completed in the first study period on days 6 and 7 to reproduce the identical diets for days 6 and 7 of the subsequent collection period.

Study period "Moonstone"

Water OTHER

Participants will take in 1L of tap water per day plus ad lib, self-selected fluids. Participants will follow their own self-chosen ad lib diets and complete a diet diary (Appendix) for days 6 and 7 in the first study period. On day 7, a 24-hour urine collection will be performed, and a 50-ml aliquot of urine will be sent to Litholink (Chicago, IL) via FedEx for analysis. Participants will then continue to the second study period and will use the diet diary completed in the first study period on days 6 and 7 to reproduce the identical diets for days 6 and 7 of the subsequent collection period.

Study period "Water"

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The study will enroll patients with calcium, cystine and uric acid stone composition. Patients will be at least 18 years of age, with no upper limit of age. Patients will sign an informed consent form (ICF). We will seek participants who have experienced any USD events including renal colic with spontaneous stone passage, emergency room visits, or urological interventions, in the previous 5 years in order to encourage enrollment and adherence to the protocol. We will include all racial and ethnic groups, and both men and women. Besides stone composition, standard demographic data including gender, age, and body mass index will be collected.
• Patients who are taking alkalinizing medications for prevention of USD including KCit, potassium bicarbonate, sodium citrate and sodium bicarbonate will be eligible for participation in the study. The patient's usual dose, however, will be discontinued for the 2 weeks which make up the two study periods. This maneuver will not be an important risk for stones for several reasons: 1) the period off alkali altogether will be one week; 2) the one week of Moonstone will offer a significant amount of alkali, likely as much or more than the patients' usual prescription doses; 3) participants will continue to adhere to fluid intake and dietary prescriptions.
• These data are intended to be included in an RO-1 resubmission due November 5. We will therefore aspire to include 10 patients with calcium stones, 3 patients with cystine stones and 3 patients with uric acid stones.

You may not qualify if:

• Investigators will exclude patients taking thiazides (indapamide, hydrochlorothiazide, and chlorthalidone). Our reasoning is that most calcium stone patients are not taking thiazides and such patients may be total body potassium-depleted (not necessarily reflected by serum potassium. Potassium depletion reduces citrate excretion (through effects on intracellular pH in the proximal tubule) so that patients taking thiazides could start with lower urine citrate excretion and have less of an increment in the Moonstone periods. The order of the periods might affect the magnitude of urine chemistry changes in those two periods.
• Patients with chronic kidney disease tend to have reduced urinary citrate excretion due to mild metabolic acidosis. We will therefore exclude patients with estimated glomerular filtration rates (eGFRs) less than 60 ml/min/1.73 m2 calculated by the CKD-EPI equation. eGFRs will have been measured in the preceding year at a time when urinary tract obstruction due to USD was not present. We will also exclude women who are pregnant or nursing and people with any medical, psychiatric, debilitating disease/disorder, or social condition that in the judgment of the investigator would interfere with or serve as a contraindication to adherence to the study protocol or ability to give informed consent, or affect the overall prognosis of the patient.

Sponsors & Collaborators

• NYU Langone Health: lead

Study Sites (1)

NYU Langone Health

New York, New York, 10016, United States

Location

MeSH Terms

Conditions

Urinary Calculi

Interventions

Water

Condition Hierarchy (Ancestors)

Urolithiasis; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Calculi; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Hydroxides; Alkalies; Inorganic Chemicals; Anions; Ions; Electrolytes; Oxides; Oxygen Compounds

Study Officials

• David Goldfarb, MD

  NYU Langone Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Given the nature of the two arms, it is not possible to blind the participants or investigators.
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: All participants will undergo the same two study periods. The order of the periods will be randomly assigned to each patient in order to eliminate the possibility of a sequence effect. The study periods can be done in non-consecutive weeks, chosen at the patients' discretion. The periods will each be 1 week in duration.

Study Record Dates

• First Submitted: January 4, 2021
• First Posted: January 6, 2021
• Study Start: September 1, 2020
• Primary Completion: December 14, 2020
• Study Completion: December 14, 2020
• Last Updated: January 6, 2021

Record last verified: 2021-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: beginning 9 months and ending 36 months following article publication
• Access Criteria: Requests may be directed to the PI.

Locations

US (1)