Clinical trial NCT04651088: Comparing Alkalinizing Agents Efficacy on Stone Risk in Patients on a Metabolically Controlled Diet
Official title: Evaluation of Multiple Alkalinizing Agents on Urinary Stone Risk Parameters in Stone and Non-stone Formers on a Metabolically Controlled Diet
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: EARLY_PHASE1
Conditions: Kidney Stone
Lead sponsor: University of Texas Southwestern Medical Center
Sponsor class: OTHER
First posted: 2020-12-03
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: 24 hour urine volume
timeFrame: Change from baseline (Day 4) to initial start on treatment (Day 5)
measure: 24 hour urine volume
timeFrame: Change from baseline (Day 4) to end of study (day 12)
measure: 24 hour urine creatinine
timeFrame: Change from baseline (Day 4) to initial start on treatment (Day 5)
measure: 24 hour urine creatinine
timeFrame: Change from baseline (Day 4) to end of study (day 12)
measure: 24 hour urine calcium
timeFrame: Change from baseline (Day 4) to initial start on treatment (Day 5)
measure: 24 hour urine calcium
timeFrame: Change from baseline (Day 4) to end of study (day 12)
measure: 24 hour urine potassium
timeFrame: Change from baseline (Day 4) to initial start on treatment (Day 5)
measure: 24 hour urine potassium
timeFrame: Change from baseline (Day 4) to end of study (day 12)
measure: 24 hour urine sodium
timeFrame: Change from baseline (Day 4) to initial start on treatment (Day 5)
measure: 24 hours urine sodium
timeFrame: Change from baseline (Day 4) to end of study (day 12)
measure: 24 hours urine citrate
timeFrame: Change from baseline (Day 4) to initial start on treatment (Day 5)
measure: 24 hours urine citrate
timeFrame: Change from baseline (Day 4) to end of study (day 12)
measure: 24 hours urine uric acid
timeFrame: Change from baseline (Day 4) to initial start on treatment (Day 5)
measure: 24 hours urine uric acid
timeFrame: Change from baseline (Day 4) to end of study (day 12)
measure: 24 hours urine oxalate
timeFrame: Change from baseline (Day 4) to initial start on treatment (Day 5)
measure: 24 hours urine oxalate
timeFrame: Change from baseline (Day 4) to end of study (day 12)
measure: 24 hours urine magnesium
timeFrame: Change from baseline (Day 4) to initial start on treatment (Day 5)
measure: 24 hours urine magnesium
timeFrame: Change from baseline (Day 4) to end of study (day 12)
measure: 24 hours urine ammonia
timeFrame: Change from baseline (Day 4) to initial start on treatment (Day 5)
measure: 24 hours urine ammonia
timeFrame: Change from baseline (Day 4) to end of study (day 12)
measure: 24 Hour Urine pH
timeFrame: Change from baseline (Day 4) to initial start on treatment (Day 5)
measure: 24 Hour Urine pH
timeFrame: Change from baseline (Day 4) to end of study (day 12)
measure: 24 hour urine phosphorus
timeFrame: Change from baseline (Day 4) to initial start on treatment (Day 5)
measure: 24 hour urine phosphorus
timeFrame: Change from baseline (Day 4) to end of study (day 12)
measure: 24 hour urine sulfate
timeFrame: Change from baseline (Day 4) to initial start on treatment (Day 5)
measure: 24 hour urine sulfate
timeFrame: Change from baseline (Day 4) to end of study (day 12)
Secondary outcomes:
measure: # of patient who adherence to 100% Medication
timeFrame: At the end of study approximately 10 weeks after start of study.
measure: Total out of pocket cost
timeFrame: At the end of study approximately 10 weeks after start of study.
measure: Patient's Satisfaction Survey
timeFrame: At the end of study approximately 10 weeks after start of study.
measure: Patient's GI Distress
timeFrame: At the end of study approximately 10 weeks after start of study.
Other outcomes:
Locations:
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
Study officials:
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.