Clinical trial NCT01980004: Potassium Citrate Supplementation vs. Dietary Counseling
Official title: Does Potassium Citrate Supplementation Reduce Stone Recurrence in Calcium Phosphate Stone Formers With Risk Factors?
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Kidney Stone
Lead sponsor: University of North Carolina, Chapel Hill
Sponsor class: OTHER
Collaborators: name: Vanderbilt University
First posted: 2013-11-08
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to compare the role of potassium citrate supplementation with dietary education versus dietary education alone in the reduction of stone risks and events in patients with predominantly calcium phosphate kidney stones.

Detailed description: The prevalence of kidney stone disease in the United States is increasing. Concurrently, an increase in calcium phosphate stone composition is also being observed. Recurrence of kidney stone disease has been reported as high as 50% at five years. Citrate supplementation is widely considered as one of the primary medical cornerstones to decrease kidney stone recurrence. Urinary citrate is a potent inhibitor of calcium stone formation by binding ionic urinary calcium as well as direct inhibition of calcium oxalate formation. Additionally, increased citrate, an alkali, raises urine pH which alters the solubility of certain stone types including uric acid and cystine stones. Potassium citrate supplementation is the primary proven approach to increasing urinary citrate and is a well-established preventive option in stone disease. However, medication treatment can cause epigastric discomfort, frequent large bowel movements and add to the patient's prescription financial burden. Dietary education including lemonade therapy provides natural dietary sources of citrate and may be an alternative to pharmacologic therapy without the associated gastrointestinal symptoms or costs.

The utility of citrate supplementation has not been previously evaluated prospectively in the calcium phosphate stone former. Calcium phosphate stone formation occurs in a more alkaline urine environment. It has been postulated that citrate supplementation could promote calcium phosphate stone occurrence due to its ability to raise urine pH despite the inhibitory effects of increasing urinary citrate. However, this finding has not been observed in limited retrospective studies. The purpose of this investigation is to prospectively evaluate the benefit of citrate supplementation either through potassium citrate treatment with dietary education vs. dietary education alone to reduce stone recurrence in calcium phosphate stone formers with risk factors.

Eligibility criteria: Inclusion Criteria:

1. Patients ≥ 18 years old, being seen at UNC Chapel Hill or Vanderbilt Urology Clinics
2. Documented stone analysis with ≥ 50% calcium phosphate (hydroxyapatite and/or brushite) composition
3. 24 hour urine citrate (≤ 500) on initial evaluation of at least one 24-hour urine study
4. 24 hour urine pH ≥ 6.0 on initial evaluation of at least one 24-hour urine study

Exclusion Criteria:

1. Documented stone analysis with any calcium carbonate or magnesium ammonium phosphate composition
2. Systemic cause for stone disease (primary hyperparathyroidism, complete distal renal tubular acidosis, systemic acidosis, active urinary tract infection)
3. 24 hour urine calcium/kg (\> 4) or 24 hour urine calcium/Cr (\>140) on initial evaluation of at least one 24-hour urine study
4. Concurrent medication therapy (potassium citrate, sodium citrate, sodium bicarbonate, diuretic, angiotensin-converting enzyme inhibitor, angiotensin II receptor antagonist, topiramate, acetazolamide)
5. Renal insufficiency (GFR ≤ 60)
6. Elevated serum potassium level (≥ 4.5) or hyperkalemia
7. Low serum bicarbonate level (\< 24)
8. High serum calcium level (\>10)
9. Pregnancy
10. Inability to obtain informed consent

Primary outcomes:
measure: Change in 24-hour urine parameters
timeFrame: 4-6 weeks from baseline
Secondary outcomes:
Other outcomes:
Locations:
city: Chapel Hill
country: United States
facility: North Carolina Memorial Hospital
state: North Carolina
Study officials:
affiliation: University of North Carolina, Chapel Hill
name: Davis J Viprakasit, MD
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Penniston KL, Steele TH, Nakada SY. Lemonade therapy increases urinary citrate and urine volumes in patients with recurrent calcium oxalate stone formation. Urology. 2007 Nov;70(5):856-60. doi: 10.1016/j.urology.2007.06.1115. Epub 2007 Oct 24.