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Use of an Herbal Preparation to Prevent and Dissolve Kidney Stones

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ClinicalTrials.gov Identifier: NCT00381849
Recruitment Status : Completed
First Posted : September 28, 2006
Results First Posted : August 6, 2012
Last Update Posted : February 4, 2016
Sponsor:
Collaborators:
Himalaya Herbal Healthcare
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by (Responsible Party):
Stephen B. Erickson, M.D., Mayo Clinic

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Conditions Cystinuria
Nephrolithiasis, Calcium Oxalate
Interventions Drug: Cystone
Drug: Sugar Pill (Placebo)
Enrollment 20

Recruitment Details Patients with recurring and analytically confirmed kidney stones were recruited from the Mayo Stone Clinic in Rochester, MN.
Pre-assignment Details  
Arm/Group Title Calcium Stone Subjects Cystine Stone Subjects
Hide Arm/Group Description Subjects with confirmed calcium kidney stone(s) Subjects with confirmed cystine kidney stone(s)
Period Title: First Intervention
Started 10 10
Completed 10 10
Not Completed 0 0
Period Title: Wash Out
Started 10 10
Completed 10 9
Not Completed 0 1
Reason Not Completed
Withdrawal by Subject             0             1
Period Title: Second Intervention
Started 10 9
Completed 10 9
Not Completed 0 0
Period Title: Open-label
Started 10 9
Completed 10 9
Not Completed 0 0
Arm/Group Title Calcium Stone Subjects Cystine Stone Subjects Total
Hide Arm/Group Description Subjects with confirmed calcium kidney stone(s) Subjects with confirmed cystine kidney stone(s) Total of all reporting groups
Overall Number of Baseline Participants 10 10 20
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants 10 participants 20 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
8
  80.0%
9
  90.0%
17
  85.0%
>=65 years
2
  20.0%
1
  10.0%
3
  15.0%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants 10 participants 20 participants
Female
6
  60.0%
4
  40.0%
10
  50.0%
Male
4
  40.0%
6
  60.0%
10
  50.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 10 participants 10 participants 20 participants
10 10 20
1.Primary Outcome
Title 24 Hour Urine Supersaturation of Calcium Oxalate (CaOx)
Hide Description 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.
Time Frame baseline, after 6 weeks treatment on placebo, after 6 weeks treatment on cystone, at end of 46 weeks of open label cystone treatment
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
CaOx was not analyzed for the Cystine Stone subjects.
Arm/Group Title Calcium Stone Subjects Cystine Stone Subjects
Hide Arm/Group Description:
Subjects with confirmed calcium kidney stone(s)
Subjects with confirmed cystine kidney stone(s)
Overall Number of Participants Analyzed 10 0
Mean (Standard Deviation)
Unit of Measure: KJoules/mol
CaOx at Baseline 1.83  (0.28)
CaOx after placebo (6 wks) 1.83  (0.42)
CaOx after Cystone (6 wks) 1.87  (0.43)
CaOx at end of Cystone (46 weeks) 1.78  (0.47)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Calcium Stone Subjects
Comments Paired t test for supersaturation of CaOx between baseline and after 6 weeks' treatment on placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.32
Comments [Not Specified]
Method t-test, 1 sided
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Calcium Stone Subjects
Comments Paired t test for supersaturation of CaOx between baseline and after 6 weeks' treatment on cystone.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.23
Comments [Not Specified]
Method t-test, 1 sided
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Calcium Stone Subjects
Comments Paired t test for supersaturation of CaOx between six weeks' treatment on cystone and 6 weeks' treatment on placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.41
Comments [Not Specified]
Method t-test, 1 sided
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Calcium Stone Subjects
Comments Paired t test for supersaturation of CaOx between baseline and after 46 weeks' treatment on cystone.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.32
Comments [Not Specified]
Method t-test, 1 sided
Comments [Not Specified]
2.Primary Outcome
Title 24 Hour Urine Supersaturation of Calcium Phosphate (Brushite)
Hide Description 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.
Time Frame baseline, after 6 weeks treatment on placebo, after 6 weeks treatment on cystone, at end of 46 weeks of open label cystone treatment
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Brushite was not analyzed for the Cystine Stone subjects.
Arm/Group Title Calcium Stone Subjects Cystine Stone Subjects
Hide Arm/Group Description:
Subjects with confirmed calcium kidney stone(s)
Subjects with confirmed cystine kidney stone(s)
Overall Number of Participants Analyzed 10 0
Mean (Standard Deviation)
Unit of Measure: KJoules/mol
Brushite at Baseline 0.35  (1.04)
Brushite after placebo (6 wks) 0.73  (0.83)
Brushite after Cystone (6 wks) 0.38  (0.98)
Brushite at end of Cystone (46 weeks) 0.09  (1.29)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Calcium Stone Subjects
Comments Paired t test for supersaturation of Brushite between baseline and after 6 weeks' treatment on placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.49
Comments [Not Specified]
Method t-test, 1 sided
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Calcium Stone Subjects
Comments Paired t test for supersaturation of Brushite between baseline and after 6 weeks' treatment on cystone.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.64
Comments [Not Specified]
Method t-test, 1 sided
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Calcium Stone Subjects
Comments Paired t test for supersaturation of Brushite between six weeks' treatment on cystone and 6 weeks' treatment on placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.72
Comments [Not Specified]
Method t-test, 1 sided
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Calcium Stone Subjects
Comments Paired t test for supersaturation of Brushite between baseline and after 46 weeks' treatment on cystone.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.84
Comments [Not Specified]
Method t-test, 1 sided
Comments [Not Specified]
3.Primary Outcome
Title 24 Hour Urine Supersaturation of Calcium Phosphate (Hydroxyapatite)
Hide Description 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.
Time Frame baseline, after 6 weeks treatment on placebo, after 6 weeks treatment on cystone, at end of 46 weeks of open label cystone treatment
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Hydroxyapatite was not analyzed for the Cystine Stone subjects.
Arm/Group Title Calcium Stone Subjects Cystine Stone Subjects
Hide Arm/Group Description:
Subjects with confirmed calcium kidney stone(s)
Subjects with confirmed cystine kidney stone(s)
Overall Number of Participants Analyzed 10 0
Mean (Standard Deviation)
Unit of Measure: KJoules/mol
Hydroxyapatite at Baseline 4.25  (2.02)
Hydroxyapatite after placebo (6 wks) 5.03  (1.23)
Hydroxyapatite after Cystone (6 wks) 4.65  (1.86)
Hydroxyapatite at end of Cystone (46 weeks) 4.09  (2.06)
4.Primary Outcome
Title 24 Hour Urinary Cystine Excretion
Hide Description [Not Specified]
Time Frame baseline, after 6 weeks treatment on placebo, after 6 weeks treatment on cystone, at end of 46 weeks of open label cystone treatment
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Cystine excretion was not applicable to the Calcium Stone subjects.
Arm/Group Title Calcium Stone Subjects Cystine Stone Subjects
Hide Arm/Group Description:
Subjects with confirmed calcium kidney stone(s)
Subjects with confirmed cystine kidney stone(s)
Overall Number of Participants Analyzed 0 10
Mean (Standard Deviation)
Unit of Measure: mcmol/24 hours
Cystine at Baseline 2770  (947)
Cystine after placebo (6 wks) 3183  (1898)
Cystine after Cystone (6 wks) 2948  (2021)
Cystine at end of Cystone (46 weeks) 4140  (2398)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cystine Stone Subjects
Comments Paired t test for urinary cystine between baseline and after 6 weeks' treatment on placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.69
Comments [Not Specified]
Method t-test, 1 sided
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cystine Stone Subjects
Comments Paired t test for urinary cystine between baseline and after 6 weeks' treatment on cystone.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.25
Comments [Not Specified]
Method t-test, 1 sided
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Cystine Stone Subjects
Comments Paired t test for urinary cystine between six weeks' treatment on cystone and 6 weeks' treatment on placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.15
Comments [Not Specified]
Method t-test, 1 sided
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Cystine Stone Subjects
Comments Paired t test for urinary cystine between baseline and after 46 weeks' treatment on cystone.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.20
Comments [Not Specified]
Method t-test, 1 sided
Comments [Not Specified]
5.Primary Outcome
Title Stone Density as Measured by Agatston Score Via Computerized Tomography
Hide Description Agatston results are a measure of calcium typically used for measuring coronary artery calcification.
Time Frame Baseline, approximately 52 weeks after baseline
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
One subject was excluded from CT analysis because of bilateral stone removal surgery during the study
Arm/Group Title Calcium Stone Subjects Cystine Stone Subjects
Hide Arm/Group Description:
Subjects with confirmed calcium kidney stone(s)
Subjects with confirmed cystine kidney stone(s)
Overall Number of Participants Analyzed 9 10
Mean (Standard Deviation)
Unit of Measure: Agatston Score
Baseline Right Kidney Agatston Score 49.75  (60.24) 2,107  (4,417)
52 week Right Kidney Agatston Score 56.13  (74.23) 2,183  (4,157)
Baseline Left Kidney Agatston Score 166.13  (143.16) 383  (560)
52 week Left Kidney Agatston Score 247.71  (371.46) 1,801  (2,741)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Calcium Stone Subjects
Comments Right Kidney Stone Density; P-value comparing one year to baseline
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.85
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Calcium Stone Subjects
Comments Left Kidney Stone Density; P-value comparing one year to baseline
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.63
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Cystine Stone Subjects
Comments Right Kidney Stone Density; P-value comparing one year to baseline
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.97
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Cystine Stone Subjects
Comments Left Kidney Stone Density; P-value comparing one year to baseline
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.15
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
6.Primary Outcome
Title Volume of Kidney Stones as Measured on Computerized Tomography
Hide Description Measurement of kidney stone volume in cubic millimeters.
Time Frame Baseline, approximately 52 weeks after baseline
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
One subject was excluded from CT analysis because of bilateral stone removal surgery during the study.
Arm/Group Title Calcium Stone Subjects Cystine Stone Subjects
Hide Arm/Group Description:
Subjects with confirmed calcium kidney stone(s)
Subjects with confirmed cystine kidney stone(s)
Overall Number of Participants Analyzed 9 10
Mean (Standard Deviation)
Unit of Measure: mm^3
Baseline Right Kidney Stone Volume 45.5  (52.03) 1,602  (3,335)
52 Week Right Kidney Stone Volume 52.75  (66.44) 1,677  (3,139)
Baseline Left Kidney Stone Volume 141.25  (198.98) 301  (422)
52 Week Left Kidney Stone Volume 174.25  (265.73) 2,064  (688)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Calcium Stone Subjects
Comments Right Kidney Stone Volume; P-value comparing one year to baseline
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.81
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Calcium Stone Subjects
Comments Left Kidney Stone Volume; P-value comparing one year to baseline
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.78
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Cystine Stone Subjects
Comments Right Kidney Stone Volume; P-value comparing one year to baseline
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.96
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Cystine Stone Subjects
Comments Left Kidney Stone Volume; P-value comparing one year to baseline
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.13
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
7.Secondary Outcome
Title Change in Stone Burden as Assessed by Radiologist at One Year
Hide Description 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.
Time Frame Baseline, approximately 52 weeks after baseline
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
One subject in the Calcium group was excluded from the CT analysis because of bilateral stone removal surgery during the study.
Arm/Group Title Calcium Stone Subjects Cystine Stone Subjects
Hide Arm/Group Description:
Subjects with confirmed calcium kidney stone(s)
Subjects with confirmed cystine kidney stone(s)
Overall Number of Participants Analyzed 9 9
Measure Type: Number
Unit of Measure: Kidneys
Right kidney no change in stone burden 6 7
Right kidney stone burden increased 2 2
Right kidney stone burden decreased 1 0
Left kidney no change in stone burden 2 2
Left kidney stone burden increased 6 5
Left kidney stone burden decreased 1 2
Time Frame 1 year
Adverse Event Reporting Description Subject self reported any adverse effects.
 
Arm/Group Title Calcium Stone Subjects Cystine Stone Subjects
Hide Arm/Group Description Subjects with confirmed calcium kidney stone(s) Subjects with confirmed cystine kidney stone(s)
All-Cause Mortality
Calcium Stone Subjects Cystine Stone Subjects
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Calcium Stone Subjects Cystine Stone Subjects
Affected / at Risk (%) Affected / at Risk (%)
Total   0/10 (0.00%)   0/10 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Calcium Stone Subjects Cystine Stone Subjects
Affected / at Risk (%) Affected / at Risk (%)
Total   0/10 (0.00%)   0/10 (0.00%) 
There were no serious adverse events and no adverse events. Power of the study was diminished by failure of patients to return all required 24 hour urine samples. The botanical authenticity of Cystone was not documented.
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Name/Title: Beverly Tietje, Study Coordinator
Organization: Mayo Clinic
Phone: 507-255-0401
Responsible Party: Stephen B. Erickson, M.D., Mayo Clinic
ClinicalTrials.gov Identifier: NCT00381849     History of Changes
Other Study ID Numbers: 2115-05
P50DK083007 ( U.S. NIH Grant/Contract )
First Submitted: September 27, 2006
First Posted: September 28, 2006
Results First Submitted: April 12, 2011
Results First Posted: August 6, 2012
Last Update Posted: February 4, 2016