Use of an Herbal Preparation to Prevent and Dissolve Kidney Stones

Study Overview
=================
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.

Official Title
-----------------
Cystone for Treatment of Nephrolithiasis

Conditions
-----------------
Cystinuria, Nephrolithiasis, Calcium Oxalate

Intervention / Treatment
-----------------
* Drug: Cystone
* Drug: Sugar Pill (Placebo)


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Cystone then sugar pill<br>Subject will take Cystone for 6 weeks, then have a 1 week wash out period followed by the sugar pill for another 6 weeks | Drug: Cystone<br>* Participants will take 2 pills, 2 times a day. Each tablet of Cystone contains: Shilapushpha (Didymocarpus pedicellata) 130 mg, Pasanabheda (Saxifraga ligulata Syn. Bergenia ligulata/cilata) 98 mg, Indian madder/ Manjishtha (Rubia cordifolia) 32 mg, Umbrella's edge/ Nagarmusta (Cyperus scariosus) 32 mg, Prickly chaff flower/ Apamarga (Achyranthes aspera) 32 mg, Sedge/ Gojiha (Onosma bracteatum) 32 mg, Purple fleabane/ Sahadeve (Veronoia Cinerea) 32 mg, Lime silicate calx/ Hajrul yahood Bhasma/ Badrashma bhasma) 32 mg, Shilajit 26 mg.<br>* Other names: Uricare;Drug: Sugar Pill (Placebo)<br>* Participants will take 2 pills, 2 times a day for 6 weeks.<br>|
| Placebo Comparator: Sugar pill then Cystone<br>Subject will take sugar pill for 6 weeks, then a 1 week wash out followed by the Cystone for another 6 weeks | Drug: Cystone<br>* Participants will take 2 pills, 2 times a day. Each tablet of Cystone contains: Shilapushpha (Didymocarpus pedicellata) 130 mg, Pasanabheda (Saxifraga ligulata Syn. Bergenia ligulata/cilata) 98 mg, Indian madder/ Manjishtha (Rubia cordifolia) 32 mg, Umbrella's edge/ Nagarmusta (Cyperus scariosus) 32 mg, Prickly chaff flower/ Apamarga (Achyranthes aspera) 32 mg, Sedge/ Gojiha (Onosma bracteatum) 32 mg, Purple fleabane/ Sahadeve (Veronoia Cinerea) 32 mg, Lime silicate calx/ Hajrul yahood Bhasma/ Badrashma bhasma) 32 mg, Shilajit 26 mg.<br>* Other names: Uricare;Drug: Sugar Pill (Placebo)<br>* Participants will take 2 pills, 2 times a day for 6 weeks.<br>|
| Experimental: Open-label Cystone<br>All subjects will receive Cystone for 46 weeks in the open-label period. | Drug: Cystone<br>* Participants will take 2 pills, 2 times a day. Each tablet of Cystone contains: Shilapushpha (Didymocarpus pedicellata) 130 mg, Pasanabheda (Saxifraga ligulata Syn. Bergenia ligulata/cilata) 98 mg, Indian madder/ Manjishtha (Rubia cordifolia) 32 mg, Umbrella's edge/ Nagarmusta (Cyperus scariosus) 32 mg, Prickly chaff flower/ Apamarga (Achyranthes aspera) 32 mg, Sedge/ Gojiha (Onosma bracteatum) 32 mg, Purple fleabane/ Sahadeve (Veronoia Cinerea) 32 mg, Lime silicate calx/ Hajrul yahood Bhasma/ Badrashma bhasma) 32 mg, Shilajit 26 mg.<br>* Other names: Uricare;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 24 Hour Urine Supersaturation of Calcium Oxalate (CaOx) | 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. | baseline, after 6 weeks treatment on placebo, after 6 weeks treatment on cystone, at end of 46 weeks of open label cystone treatment | 
| 24 Hour Urine Supersaturation of Calcium Phosphate (Brushite) | 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. | baseline, after 6 weeks treatment on placebo, after 6 weeks treatment on cystone, at end of 46 weeks of open label cystone treatment | 
| 24 Hour Urine Supersaturation of Calcium Phosphate (Hydroxyapatite) | 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. | baseline, after 6 weeks treatment on placebo, after 6 weeks treatment on cystone, at end of 46 weeks of open label cystone treatment | 
| 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 | Agatston results are a measure of calcium typically used for measuring coronary artery calcification. | Baseline, approximately 52 weeks after baseline | 
| Volume of Kidney Stones as Measured on Computerized Tomography | Measurement of kidney stone volume in cubic millimeters. | Baseline, approximately 52 weeks after baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Stone Burden as Assessed by Radiologist at One Year | 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. | Baseline, approximately 52 weeks after baseline | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Supersaturation, Cystone, Uricare, Computerized tomography, Kidney calculi, Nephrolithiasis, Quantitative CT