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| ID | Type | Description | Link |
|---|---|---|---|
| P50DK083007 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| Himalaya Herbal Healthcare | UNKNOWN |
| National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) | NIH |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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 |
|
| Open-label Cystone | Experimental | All subjects will receive Cystone for 46 weeks in the open-label period. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Cystone | Drug | 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. |
| 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 |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Stephen B. Erickson, M.D. | Mayo Clinic | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Mayo Clinic | Rochester | Minnesota | 55905 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 21419606 | Result | Abdollahiasl A, Kebriaeezadeh A, Nikfar S, Farshchi A, Ghiasi G, Abdollahi M. Patterns of antibiotic consumption in Iran during 2000-2009. Int J Antimicrob Agents. 2011 May;37(5):489-90. doi: 10.1016/j.ijantimicag.2011.01.022. Epub 2011 Mar 17. No abstract available. | |
| 21161651 | Result | Erickson SB, Vrtiska TJ, Canzanello VJ, Lieske JC. Cystone(R) for 1 year did not change urine chemistry or decrease stone burden in cystine stone formers. Urol Res. 2011 Jun;39(3):197-203. doi: 10.1007/s00240-010-0334-x. Epub 2010 Dec 16. |
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Patients with recurring and analytically confirmed kidney stones were recruited from the Mayo Stone Clinic in Rochester, MN.
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| ID | Title | Description |
|---|---|---|
| FG000 | Calcium Stone Subjects | Subjects with confirmed calcium kidney stone(s) |
| FG001 | Cystine Stone Subjects | Subjects with confirmed cystine kidney stone(s) |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| First Intervention |
| |||||||||||||
| Wash Out |
| |||||||||||||
| Second Intervention |
| |||||||||||||
| Open-label |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Calcium Stone Subjects | Subjects with confirmed calcium kidney stone(s) |
| BG001 | Cystine Stone Subjects | Subjects with confirmed cystine kidney stone(s) |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | CaOx was not analyzed for the Cystine Stone subjects. | Posted | Apr 2011 | Mean | Standard Deviation | KJoules/mol | baseline, after 6 weeks treatment on placebo, after 6 weeks treatment on cystone, at end of 46 weeks of open label cystone treatment |
|
1 year
Subject self reported any adverse effects.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Calcium Stone Subjects | Subjects with confirmed calcium kidney stone(s) |
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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.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Beverly Tietje, Study Coordinator | Mayo Clinic | 507-255-0401 | tietje.beverly@mayo.edu |
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| ID | Term |
|---|---|
| D003555 | Cystinuria |
| C563477 | Nephrolithiasis, Calcium Oxalate |
| D007669 | Kidney Calculi |
| D053040 | Nephrolithiasis |
| ID | Term |
|---|---|
| D000608 | Renal Aminoacidurias |
| D015499 | Renal Tubular Transport, Inborn Errors |
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
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| ID | Term |
|---|---|
| C041060 | cystone |
| D000073893 | Sugars |
| ID | Term |
|---|---|
| D002241 | Carbohydrates |
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|
|
| Sugar Pill (Placebo) | Drug | Participants will take 2 pills, 2 times a day for 6 weeks. |
|
| 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 |
| NOT COMPLETED |
|
|
| NOT COMPLETED |
|
| NOT COMPLETED |
|
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG001 | Cystine Stone Subjects | Subjects with confirmed cystine kidney stone(s) |
|
|
|
| Primary | 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. | Brushite was not analyzed for the Cystine Stone subjects. | Posted | Mean | Standard Deviation | KJoules/mol | baseline, after 6 weeks treatment on placebo, after 6 weeks treatment on cystone, at end of 46 weeks of open label cystone treatment |
|
|
|
|
| Primary | 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. | Hydroxyapatite was not analyzed for the Cystine Stone subjects. | Posted | Mean | Standard Deviation | KJoules/mol | baseline, after 6 weeks treatment on placebo, after 6 weeks treatment on cystone, at end of 46 weeks of open label cystone treatment |
|
|
|
| Secondary | 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. | One subject in the Calcium group was excluded from the CT analysis because of bilateral stone removal surgery during the study. | Posted | Number | Kidneys | Baseline, approximately 52 weeks after baseline |
|
|
|
| Primary | 24 Hour Urinary Cystine Excretion | Cystine excretion was not applicable to the Calcium Stone subjects. | Posted | Mean | Standard Deviation | mcmol/24 hours | baseline, after 6 weeks treatment on placebo, after 6 weeks treatment on cystone, at end of 46 weeks of open label cystone treatment |
|
|
|
|
| Primary | Stone Density as Measured by Agatston Score Via Computerized Tomography | Agatston results are a measure of calcium typically used for measuring coronary artery calcification. | One subject was excluded from CT analysis because of bilateral stone removal surgery during the study | Posted | May 2011 | Mean | Standard Deviation | Agatston Score | Baseline, approximately 52 weeks after baseline |
|
|
|
|
| Primary | Volume of Kidney Stones as Measured on Computerized Tomography | Measurement of kidney stone volume in cubic millimeters. | One subject was excluded from CT analysis because of bilateral stone removal surgery during the study. | Posted | Mean | Standard Deviation | mm^3 | Baseline, approximately 52 weeks after baseline |
|
|
|
|
| 0 |
| 10 |
| 0 |
| 10 |
| EG001 | Cystine Stone Subjects | Subjects with confirmed cystine kidney stone(s) | 0 | 10 | 0 | 10 |
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| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D052878 | Urolithiasis |
| D014545 | Urinary Calculi |
| D002137 | Calculi |
| D020763 | Pathological Conditions, Anatomical |
| D013568 | Pathological Conditions, Signs and Symptoms |
| Title | Measurements |
|---|---|
|
| Brushite at end of Cystone (46 weeks) |
|
| t-test, 1 sided |
| 0.64 |
| 95 |
| No |
| Superiority or Other |
| Paired t test for supersaturation of Brushite between six weeks' treatment on cystone and 6 weeks' treatment on placebo. | t-test, 1 sided | 0.72 | 95 | No | Superiority or Other |
| Paired t test for supersaturation of Brushite between baseline and after 46 weeks' treatment on cystone. | t-test, 1 sided | 0.84 | 95 | No | Superiority or Other |
|
| Hydroxyapatite at end of Cystone (46 weeks) |
|
| Right kidney stone burden decreased |
|
| Left kidney no change in stone burden |
|
| Left kidney stone burden increased |
|
| Left kidney stone burden decreased |
|
| Title | Measurements |
|---|---|
|
| Cystine at end of Cystone (46 weeks) |
|
| 0.25 |
| 95 |
| No |
| Superiority or Other |
| Paired t test for urinary cystine between six weeks' treatment on cystone and 6 weeks' treatment on placebo. | t-test, 1 sided | 0.15 | 95 | No | Superiority or Other |
| Paired t test for urinary cystine between baseline and after 46 weeks' treatment on cystone. | t-test, 1 sided | 0.20 | 95 | No | Superiority or Other |
| Baseline Left Kidney Agatston Score |
|
| 52 week Left Kidney Agatston Score |
|
| 0.63 |
| 95 |
| No |
| Superiority or Other |
| Right Kidney Stone Density; P-value comparing one year to baseline | t-test, 2 sided | 0.97 | 95 | No | Superiority or Other |
| Left Kidney Stone Density; P-value comparing one year to baseline | t-test, 2 sided | 0.15 | 95 | No | Superiority or Other |
| Baseline Left Kidney Stone Volume |
|
| 52 Week Left Kidney Stone Volume |
|
| 0.78 |
| 95 |
| No |
| Superiority or Other |
| Right Kidney Stone Volume; P-value comparing one year to baseline | t-test, 2 sided | 0.96 | 95 | No | Superiority or Other |
| Left Kidney Stone Volume; P-value comparing one year to baseline | t-test, 2 sided | 0.13 | 95 | No | Superiority or Other |