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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Kidney Stone

Intervention / Treatment
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* Drug: Potassium citrate
* Drug: Sodium bicarbonate
* Dietary Supplement: Litholyte
* Dietary Supplement: Crystal Lite
* Drug: Potassium Bicarbonate


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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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. |