Comparing Alkalinizing Agents Efficacy on Stone Risk in Patients on a Metabolically Controlled Diet

Evaluation of Multiple Alkalinizing Agents on Urinary Stone Risk Parameters in Stone and Non-stone Formers on a Metabolically Controlled Diet

The purpose of this study is to compare over the counter and alternative prescription urinary alkalinizing agents to slow release potassium citrate in their ability to modify urinary parameters associated with stone formation.

Study Overview

• Status: Not yet recruiting
• Conditions: Kidney Stone
• Intervention / Treatment: Drug: Potassium citrate; Drug: Sodium bicarbonate; Dietary supplement: Litholyte; Dietary supplement: Crystal Lite; Drug: Potassium Bicarbonate

Detailed Description

Kidney stones are a common medical problem, occurring in almost 10% of people in the United States1. Furthermore, 50% of patients will recur within 10 years2. Metabolic testing is advised in recurrent stone formers, as well as those considered high risk, to assess for a specific abnormality which may prompt intervention to prevent future stone formation. Non-surgical interventions include both dietary counselling, as well as pharmacotherapy.

One of the most commonly prescribed class of pharmacotherapies is alkali therapy which can be used to both increase the urinary pH and raise the urine citrate levels. This is particularly useful as correction of very acidic urinary pH (<5.5) can counteract uric acid crystallization thereby preventing or even dissolving uric acid stones3. Further, citrate has been shown to be a potent inhibitor of calcium stones by binding to the calcium directly4 and inhibiting crystal nucleation, thereby reducing calcium stone formation5,6.

The most commonly utilized preparation of alkali therapy is potassium citrate which has been shown to prevent stone formation better than sodium citrate7. Unfortunately, some forms of potassium citrate (crystal packets) have become unavailable, and the slow release form of potassium citrate (UroCit-K) now exceeds $15/day in cost8. There have been multiple alternative alkali therapies that have been used in place of potassium citrate, including both medical foods and prescription medications, but with little evidence to support their use. A pilot study in order to quantify the metabolic effects of these agents and compare them to potassium citrate will be performed.

• Study Type: Interventional
• Enrollment (Estimated): 15
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Margaret Pearle; Phone Number: 214-648-6853; Email: margaret.pearle@utsouthwestern.edu
• Study Contact Backup: Name: Jessica Dai; Email: jessica.dai@utsouthwestern.edu

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern Medical Center
      • Contact: Margaret Pearle; Phone Number: 214-648-6853; Email: margaret.pearle@utsouthwestern.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 88 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Adults aged 18 and older.
• with or without a history of stone disease.

Exclusion Criteria:

• They are unable to take any of the medications due to health reasons.
• Participants are pregnant or nursing.
• Participants are unable to adhere to the metabolic diet.
• Participants had a prior adverse event from one or more of the medications.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Sodium Bicarbonate	Drug: Potassium citrate; Slow release potassium citrate UroCit-K. Participants will take 20mEq twice daily.; Drug: Sodium bicarbonate; 650mg tabs. Take 3 tabs twice daily.; Dietary supplement: Litholyte; One packet is taken with 170ml of water. Two packets daily.; Dietary supplement: Crystal Lite; The classic lemonade contains 21.7mEq/liter of alkali Therefore, patients will take 2 litres daily to have the 40mEq of alkali daily needed.; Drug: Potassium Bicarbonate; 20 mEq tablets, one tablet twice daily
Placebo Comparator: Metabolic diet; Controlled metabolic diet arm.	Drug: Potassium citrate; Slow release potassium citrate UroCit-K. Participants will take 20mEq twice daily.; Drug: Sodium bicarbonate; 650mg tabs. Take 3 tabs twice daily.; Dietary supplement: Litholyte; One packet is taken with 170ml of water. Two packets daily.; Dietary supplement: Crystal Lite; The classic lemonade contains 21.7mEq/liter of alkali Therefore, patients will take 2 litres daily to have the 40mEq of alkali daily needed.; Drug: Potassium Bicarbonate; 20 mEq tablets, one tablet twice daily
Active Comparator: Potassium citrate	Drug: Potassium citrate; Slow release potassium citrate UroCit-K. Participants will take 20mEq twice daily.; Drug: Sodium bicarbonate; 650mg tabs. Take 3 tabs twice daily.; Dietary supplement: Litholyte; One packet is taken with 170ml of water. Two packets daily.; Dietary supplement: Crystal Lite; The classic lemonade contains 21.7mEq/liter of alkali Therefore, patients will take 2 litres daily to have the 40mEq of alkali daily needed.; Drug: Potassium Bicarbonate; 20 mEq tablets, one tablet twice daily
Active Comparator: Litholyte arm	Drug: Potassium citrate; Slow release potassium citrate UroCit-K. Participants will take 20mEq twice daily.; Drug: Sodium bicarbonate; 650mg tabs. Take 3 tabs twice daily.; Dietary supplement: Litholyte; One packet is taken with 170ml of water. Two packets daily.; Dietary supplement: Crystal Lite; The classic lemonade contains 21.7mEq/liter of alkali Therefore, patients will take 2 litres daily to have the 40mEq of alkali daily needed.; Drug: Potassium Bicarbonate; 20 mEq tablets, one tablet twice daily
Active Comparator: Crystal Lite	Drug: Potassium citrate; Slow release potassium citrate UroCit-K. Participants will take 20mEq twice daily.; Drug: Sodium bicarbonate; 650mg tabs. Take 3 tabs twice daily.; Dietary supplement: Litholyte; One packet is taken with 170ml of water. Two packets daily.; Dietary supplement: Crystal Lite; The classic lemonade contains 21.7mEq/liter of alkali Therefore, patients will take 2 litres daily to have the 40mEq of alkali daily needed.; Drug: Potassium Bicarbonate; 20 mEq tablets, one tablet twice daily
Active Comparator: Potassium Bicarbonate	Drug: Potassium citrate; Slow release potassium citrate UroCit-K. Participants will take 20mEq twice daily.; Drug: Sodium bicarbonate; 650mg tabs. Take 3 tabs twice daily.; Dietary supplement: Litholyte; One packet is taken with 170ml of water. Two packets daily.; Dietary supplement: Crystal Lite; The classic lemonade contains 21.7mEq/liter of alkali Therefore, patients will take 2 litres daily to have the 40mEq of alkali daily needed.; Drug: Potassium Bicarbonate; 20 mEq tablets, one tablet twice daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
24 hour urine volume	Total urine volume	Change from baseline (Day 4) to initial start on treatment (Day 5)
24 hour urine volume	Total urine volume	Change from baseline (Day 4) to end of study (day 12)
24 hour urine creatinine	Urine creatinine	Change from baseline (Day 4) to initial start on treatment (Day 5)
24 hour urine creatinine	Urine creatinine	Change from baseline (Day 4) to end of study (day 12)
24 hour urine calcium	urine calcium	Change from baseline (Day 4) to initial start on treatment (Day 5)
24 hour urine calcium	urine calcium	Change from baseline (Day 4) to end of study (day 12)
24 hour urine potassium	Urine potassium	Change from baseline (Day 4) to initial start on treatment (Day 5)
24 hour urine potassium	Urine potassium	Change from baseline (Day 4) to end of study (day 12)
24 hour urine sodium	Urine sodium	Change from baseline (Day 4) to initial start on treatment (Day 5)
24 hours urine sodium	Urine sodium	Change from baseline (Day 4) to end of study (day 12)
24 hours urine citrate	Urine citrate	Change from baseline (Day 4) to initial start on treatment (Day 5)
24 hours urine citrate	Urine citrate	Change from baseline (Day 4) to end of study (day 12)
24 hours urine uric acid	Urine uric acid	Change from baseline (Day 4) to initial start on treatment (Day 5)
24 hours urine uric acid	Urine Uric Acid	Change from baseline (Day 4) to end of study (day 12)
24 hours urine oxalate	Urine oxalate	Change from baseline (Day 4) to initial start on treatment (Day 5)
24 hours urine oxalate	Urine oxalate	Change from baseline (Day 4) to end of study (day 12)
24 hours urine magnesium	Urine magnesium	Change from baseline (Day 4) to initial start on treatment (Day 5)
24 hours urine magnesium	Urine magnesium	Change from baseline (Day 4) to end of study (day 12)
24 hours urine ammonia	Urine ammonia	Change from baseline (Day 4) to initial start on treatment (Day 5)
24 hours urine ammonia	Urine ammonia	Change from baseline (Day 4) to end of study (day 12)
24 Hour Urine pH	Overal Urine pH from 24h urine sample.	Change from baseline (Day 4) to initial start on treatment (Day 5)
24 Hour Urine pH	Overal Urine pH from 24h urine sample.	Change from baseline (Day 4) to end of study (day 12)
24 hour urine phosphorus	Urine phosphorus	Change from baseline (Day 4) to initial start on treatment (Day 5)
24 hour urine phosphorus	Urine phosphorus	Change from baseline (Day 4) to end of study (day 12)
24 hour urine sulfate	Urine sulfate	Change from baseline (Day 4) to initial start on treatment (Day 5)
24 hour urine sulfate	Urine sulfate	Change from baseline (Day 4) to end of study (day 12)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
# of patient who adherence to 100% Medication	Patient's adherence to medication for duration of study.	At the end of study approximately 10 weeks after start of study.
Total out of pocket cost	Calculate and compare treatment costs for the different interventions (in American dollars).	At the end of study approximately 10 weeks after start of study.
Patient's Satisfaction Survey	Patient satisfaction survey, adapted from the Treatment Satisfaction Questionnaire for Medication-14. Patients are queried on their satisfaction, with 9 questions for each medication.	At the end of study approximately 10 weeks after start of study.
Patient's GI Distress	Patient's GI distress symptom scale measures patients GI distress. There are 18 questions with descriptive answers ranging from "none", "mild", "moderate", "quite a lot" and "unbearable". There are no numerical scores, rather just descriptive scores. "None" means no GI distress, "unbearable" means that you are in a lot of distress from your GI symptoms.	At the end of study approximately 10 weeks after start of study.

Collaborators and Investigators

• Sponsor: University of Texas Southwestern Medical Center

Publications and helpful links

General Publications

• Scales CD Jr, Smith AC, Hanley JM, Saigal CS; Urologic Diseases in America Project. Prevalence of kidney stones in the United States. Eur Urol. 2012 Jul;62(1):160-5. doi: 10.1016/j.eururo.2012.03.052. Epub 2012 Mar 31.
• Ettinger B, Pak CY, Citron JT, Thomas C, Adams-Huet B, Vangessel A. Potassium-magnesium citrate is an effective prophylaxis against recurrent calcium oxalate nephrolithiasis. J Urol. 1997 Dec;158(6):2069-73. doi: 10.1016/s0022-5347(01)68155-2.
• Ryall RL. Urinary inhibitors of calcium oxalate crystallization and their potential role in stone formation. World J Urol. 1997;15(3):155-64. doi: 10.1007/BF02201852. No abstract available.
• Preminger GM, Sakhaee K, Skurla C, Pak CY. Prevention of recurrent calcium stone formation with potassium citrate therapy in patients with distal renal tubular acidosis. J Urol. 1985 Jul;134(1):20-3. doi: 10.1016/s0022-5347(17)46963-1.
• Pak CY, Sakhaee K, Fuller C. Successful management of uric acid nephrolithiasis with potassium citrate. Kidney Int. 1986 Sep;30(3):422-8. doi: 10.1038/ki.1986.201.
• Uribarri J, Oh MS, Carroll HJ. The first kidney stone. Ann Intern Med. 1989 Dec 15;111(12):1006-9. doi: 10.7326/0003-4819-111-12-1006.
• Pearle MS, Goldfarb DS, Assimos DG, Curhan G, Denu-Ciocca CJ, Matlaga BR, Monga M, Penniston KL, Preminger GM, Turk TM, White JR; American Urological Assocation. Medical management of kidney stones: AUA guideline. J Urol. 2014 Aug;192(2):316-24. doi: 10.1016/j.juro.2014.05.006. Epub 2014 May 20.
• Preminger GM, Sakhaee K, Pak CY. Alkali action on the urinary crystallization of calcium salts: contrasting responses to sodium citrate and potassium citrate. J Urol. 1988 Feb;139(2):240-2. doi: 10.1016/s0022-5347(17)42374-3.
• Stern KL, Canvasser N, Borofsky M, Gleason VM, Kamphuis G, El Tayeb MM, Hsi R, Scotland KB. Alkalinizing Agents: A Review of Prescription, Over-the-Counter, and Medical Food Supplements. J Endourol. 2020 Jan;34(1):1-6. doi: 10.1089/end.2019.0292. Epub 2019 Sep 25.

Study record dates

Study Major Dates

• Study Start (Estimated): December 1, 2024
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): July 1, 2026

Study Registration Dates

• First Submitted: November 4, 2020
• First Submitted That Met QC Criteria: November 24, 2020
• First Posted (Actual): December 3, 2020

Study Record Updates

• Last Update Posted (Actual): March 1, 2024
• Last Update Submitted That Met QC Criteria: February 29, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Pathological Conditions, Anatomical; Urolithiasis; Urinary Calculi; Calculi; Nephrolithiasis; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Calculi; Physiological Effects of Drugs; Natriuretic Agents; Diuretics; Respiratory System Agents; Expectorants; Potassium Citrate
• Other Study ID Numbers: STU-2020-0613

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