Title

Use of an Herbal Preparation to Prevent and Dissolve Kidney Stones
Cystone for Treatment of Nephrolithiasis
  • Phase

    Phase 1/Phase 2
  • Study Type

    Interventional
  • Intervention/Treatment

    cystone ...
  • Study Participants

    20
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.
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.
Study Started
Apr 30
2006
Primary Completion
Sep 30
2009
Study Completion
Jun 30
2010
Results Posted
Aug 06
2012
Estimate
Last Update
Feb 04
2016
Estimate

Drug Cystone

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.

  • Other names: Uricare

Drug Sugar Pill (Placebo)

Participants will take 2 pills, 2 times a day for 6 weeks.

Open-label Cystone Experimental

All subjects will receive Cystone for 46 weeks in the open-label period.

Cystone then sugar pill Active Comparator

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 Placebo Comparator

Subject will take sugar pill for 6 weeks, then a 1 week wash out followed by the Cystone for another 6 weeks

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

Summary

Calcium Stone Subjects

Cystine Stone Subjects

All Events

Event Type Organ System Event Term

Volume of Kidney Stones as Measured on Computerized Tomography

Measurement of kidney stone volume in cubic millimeters.

Calcium Stone Subjects

52 Week Left Kidney Stone Volume

174.25
mm^3 (Mean)
Standard Deviation: 265.73

52 Week Right Kidney Stone Volume

52.75
mm^3 (Mean)
Standard Deviation: 66.44

Baseline Left Kidney Stone Volume

141.25
mm^3 (Mean)
Standard Deviation: 198.98

Baseline Right Kidney Stone Volume

45.5
mm^3 (Mean)
Standard Deviation: 52.03

Cystine Stone Subjects

52 Week Left Kidney Stone Volume

52 Week Right Kidney Stone Volume

Baseline Left Kidney Stone Volume

301.0
mm^3 (Mean)
Standard Deviation: 422

Baseline Right Kidney Stone Volume

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.

Calcium Stone Subjects

Brushite after Cystone (6 wks)

0.38
KJoules/mol (Mean)
Standard Deviation: 0.98

Brushite after placebo (6 wks)

0.73
KJoules/mol (Mean)
Standard Deviation: 0.83

Brushite at Baseline

0.35
KJoules/mol (Mean)
Standard Deviation: 1.04

Brushite at end of Cystone (46 weeks)

0.09
KJoules/mol (Mean)
Standard Deviation: 1.29

Cystine Stone Subjects

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.

Calcium Stone Subjects

Hydroxyapatite after Cystone (6 wks)

4.65
KJoules/mol (Mean)
Standard Deviation: 1.86

Hydroxyapatite after placebo (6 wks)

5.03
KJoules/mol (Mean)
Standard Deviation: 1.23

Hydroxyapatite at Baseline

4.25
KJoules/mol (Mean)
Standard Deviation: 2.02

Hydroxyapatite at end of Cystone (46 weeks)

4.09
KJoules/mol (Mean)
Standard Deviation: 2.06

Cystine Stone Subjects

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.

Calcium Stone Subjects

CaOx after Cystone (6 wks)

1.87
KJoules/mol (Mean)
Standard Deviation: 0.43

CaOx after placebo (6 wks)

1.83
KJoules/mol (Mean)
Standard Deviation: 0.42

CaOx at Baseline

1.83
KJoules/mol (Mean)
Standard Deviation: 0.28

CaOx at end of Cystone (46 weeks)

1.78
KJoules/mol (Mean)
Standard Deviation: 0.47

Cystine Stone Subjects

24 Hour Urinary Cystine Excretion

Calcium Stone Subjects

Cystine Stone Subjects

Cystine after Cystone (6 wks)

2948.0
mcmol/24 hours (Mean)
Standard Deviation: 2021

Cystine after placebo (6 wks)

3183.0
mcmol/24 hours (Mean)
Standard Deviation: 1898

Cystine at Baseline

2770.0
mcmol/24 hours (Mean)
Standard Deviation: 947

Cystine at end of Cystone (46 weeks)

4140.0
mcmol/24 hours (Mean)
Standard Deviation: 2398

Stone Density as Measured by Agatston Score Via Computerized Tomography

Agatston results are a measure of calcium typically used for measuring coronary artery calcification.

Calcium Stone Subjects

52 week Left Kidney Agatston Score

247.71
Agatston Score (Mean)
Standard Deviation: 371.46

52 week Right Kidney Agatston Score

56.13
Agatston Score (Mean)
Standard Deviation: 74.23

Baseline Left Kidney Agatston Score

166.13
Agatston Score (Mean)
Standard Deviation: 143.16

Baseline Right Kidney Agatston Score

49.75
Agatston Score (Mean)
Standard Deviation: 60.24

Cystine Stone Subjects

52 week Left Kidney Agatston Score

52 week Right Kidney Agatston Score

Baseline Left Kidney Agatston Score

383.0
Agatston Score (Mean)
Standard Deviation: 560

Baseline Right Kidney Agatston Score

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.

Calcium Stone Subjects

Left kidney no change in stone burden

2.0
Kidneys

Left kidney stone burden decreased

1.0
Kidneys

Left kidney stone burden increased

6.0
Kidneys

Right kidney no change in stone burden

6.0
Kidneys

Right kidney stone burden decreased

1.0
Kidneys

Right kidney stone burden increased

2.0
Kidneys

Cystine Stone Subjects

Left kidney no change in stone burden

2.0
Kidneys

Left kidney stone burden decreased

2.0
Kidneys

Left kidney stone burden increased

5.0
Kidneys

Right kidney no change in stone burden

7.0
Kidneys

Right kidney stone burden decreased

Right kidney stone burden increased

2.0
Kidneys

Total

20
Participants

Total

20
Participants

Age, Categorical

Region of Enrollment

Sex: Female, Male

First Intervention

Calcium Stone Subjects

Cystine Stone Subjects

Wash Out

Calcium Stone Subjects

Cystine Stone Subjects

Second Intervention

Calcium Stone Subjects

Cystine Stone Subjects

Open-label

Calcium Stone Subjects

Cystine Stone Subjects

Drop/Withdrawal Reasons

Cystine Stone Subjects