Use of an Herbal Preparation to Prevent and Dissolve Kidney Stones

Phase 1

Completed

Conditions: Cystinuria
Nephrolithiasis, Calcium Oxalate

Interventions: Drug: Cystone
Drug: Sugar Pill (Placebo)

Registration Number: NCT00381849

Lead Sponsor: Mayo Clinic

Brief Summary: We will investigate the safety and effectiveness of a mixture of 9 east Indian herbs known as Cystone regarding their ability to dissolve existing kidney stones and prevent formation of new ones. Cystine and calcium stone formers will be recruited for a 59 week trial. The first phase of the study will be two 6 weeks periods during which each subject will receive Cystone or placebo in random order (with a one-week wash out between 6 week treatment periods). The remaining 46 weeks, each subject will receive Cystone. End points are changes in urinary chemistries and stone burden by Computerized Tomography (CT) scanning.

Detailed Description: Cystone will be used in proven cystine and calcium stone forming adults who are not pregnant. Subjects must have a measurable stone by CT. The first phase is a double blind, randomized, placebo controlled cross-over of Cystone and placebo for 6 weeks each separated by a 1 week washout. Entry, 6 and 12 week 24 hour urine supersaturations or cystine, pH and sodium determinations will be collected. Then all patients enter an open label phase of 46 weeks, ensuring a 52-week total exposure to Cystone during the 59 week study. Baseline and 1 year stone quantification CT scans will be performed. End points will be changes in urine chemistry/supersaturation and stone burden. Stone burden was measured by CT, quantitatively for stone density and volume. All CT images were also reviewed in a blinded fashion by a radiologist to score each kidney as increased, no change or decreased stone burden.

Statistics and Randomization: Randomization was accomplished using a table provided by the department of statistics to the study coordinator who was blinded as to whether the patients received placebo or Cystone®. Biochemical and supersaturation results were analyzed via a matched pair analysis using the JMP software package (SAS Instituted, Inc.); P values \< 0.05 were deemed significant.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 20

Inclusion Criteria

Written informed consent In the cystine arm, all patients will have the diagnosis of cystinuria, made on the basis of a 24-hour urine cystine containing more than 1500 umol of cystine, or a stone compositional analysis of cystine
Presence of an existing cystine stone in one or both kidneys In the calcium arm, all patients will have a history of a calcium stone as determined by laboratory analysis.
Medically effective birth control if fertile female
Able to comply with protocol

Exclusion Criteria

Pregnant
Subjects under age 18 years
Obstructing stones
Urinary Tract Infection that cannot be cleared with single course of antibiotic
Subjects who decline to provide informed consent

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Cystone then sugar pill	Sugar Pill (Placebo)	Subject will take Cystone for 6 weeks, then have a 1 week wash out period followed by the sugar pill for another 6 weeks
Sugar pill then Cystone	Sugar Pill (Placebo)	Subject will take sugar pill for 6 weeks, then a 1 week wash out followed by the Cystone for another 6 weeks
Cystone then sugar pill	Cystone	Subject will take Cystone for 6 weeks, then have a 1 week wash out period followed by the sugar pill for another 6 weeks
Sugar pill then Cystone	Cystone	Subject will take sugar pill for 6 weeks, then a 1 week wash out followed by the Cystone for another 6 weeks
Open-label Cystone	Cystone	All subjects will receive Cystone for 46 weeks in the open-label period.

Primary Outcome Measures

Name	Time	Method
24 Hour Urine Supersaturation of Calcium Oxalate (CaOx)	baseline, after 6 weeks treatment on placebo, after 6 weeks treatment on cystone, at end of 46 weeks of open label cystone treatment	Urine is often supersaturated, which favors precipitation of crystalline phases such as calcium oxalate. However, crystals do not always form in supersaturated urine because supersaturation is balanced by crystallization inhibitors that are also present. Supersaturation is calculated by measuring the concentration of all the ions that can interact. Once these concentrations are known, a computer program can calculate the theoretical supersaturation with respect to the important crystalline phases, eg, calcium oxalate.
24 Hour Urine Supersaturation of Calcium Phosphate (Brushite)	baseline, after 6 weeks treatment on placebo, after 6 weeks treatment on cystone, at end of 46 weeks of open label cystone treatment	Urine is often supersaturated, which favors precipitation of crystalline phases such as calcium oxalate. However, crystals do not always form in supersaturated urine because supersaturation is balanced by crystallization inhibitors that are also present. Supersaturation is calculated by measuring the concentration of all the ions that can interact. Once these concentrations are known, a computer program can calculate the theoretical supersaturation with respect to the important crystalline phases, eg, calcium oxalate.
24 Hour Urine Supersaturation of Calcium Phosphate (Hydroxyapatite)	baseline, after 6 weeks treatment on placebo, after 6 weeks treatment on cystone, at end of 46 weeks of open label cystone treatment	Urine is often supersaturated, which favors precipitation of crystalline phases such as calcium oxalate. However, crystals do not always form in supersaturated urine because supersaturation is balanced by crystallization inhibitors that are also present. Supersaturation is calculated by measuring the concentration of all the ions that can interact. Once these concentrations are known, a computer program can calculate the theoretical supersaturation with respect to the important crystalline phases, eg, calcium oxalate.
24 Hour Urinary Cystine Excretion	baseline, after 6 weeks treatment on placebo, after 6 weeks treatment on cystone, at end of 46 weeks of open label cystone treatment
Stone Density as Measured by Agatston Score Via Computerized Tomography	Baseline, approximately 52 weeks after baseline	Agatston results are a measure of calcium typically used for measuring coronary artery calcification.
Volume of Kidney Stones as Measured on Computerized Tomography	Baseline, approximately 52 weeks after baseline	Measurement of kidney stone volume in cubic millimeters.

Secondary Outcome Measures

Name	Time	Method
Change in Stone Burden as Assessed by Radiologist at One Year	Baseline, approximately 52 weeks after baseline	Stone burden will be quantitated using the stone quantification protocol currently available at Mayo that quantitates kidney stones both by volume and by density measured in Agatston units.