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Determine the benefit of oral vancomycin therapy for Primary Sclerosing Cholangitis.
The purpose of this study is to evaluate changes in the fecal and salivary/urinary microbiota during vancomycin treatment of children and adults with Primary Sclerosing Cholangitis (PSC), identify features of the host microbiota that are associated with disease activity and/or response to treatment and further delineate the immunological effects of oral vancomycin treatment of PSC. This study will correlate changes in microbiota with the immunological effects of oral vancomycin in children and adults with PSC. The results of this proposal will lead to new and validated targets for diagnosis and treatment of PSC that will have high impact in the short and long term for patients and their families.
Interim results were published in Abarbanel et al, J Clin Immunol 2013 (see References).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Oral Vancomycin | Experimental | 1) For children who weight < or = 30 kg, the vancomycin dose will be 50 mg/kg/day given orally 3 times per day for the 1st month and continue with the same dose for subsequent months if the clinical laboratory studies improved and are normal. If the laboratory studies are not normal the dose will be increased to 75 mg/kg/day given orally 3 times per day for the 2nd month and 100mg/kg/day given orally 3 times per day the 3rd month. If the laboratory studies do not improve by the end of the 3rd month since starting the vancomycin, the vancomycin will be stopped and the child will not continue the study. 2) For adults and children who weigh >30 kg, the vancomycin dose will be 500 mg given orally 3 times per day for the 1st month and continue with this dose if the clinical laboratory studies improve and are normal. If the laboratory studies are not normal the dose will be increased to 750 mg 3 times per day for the 2nd month and 1000 mg 3 times per day the 3rd month. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Oral Vancomycin | Drug |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| Count of Participants With Elevated Alanine Aminotransferase (ALT) at Baseline and With Clinically Significant Improvement at Month 3 | Clinically significant improvement was determined by investigator assessment per participant based on their medical history and disease stage. Elevated ALT was any value greater than the upper limit of the standard reference range used by patient's laboratory. | Baseline; Month 3 |
| Count of Participants With Elevated Gamma-glutamyltransferase (GGT) at Baseline and With Clinically Significant Improvement at Month 3 | Clinically significant improvement was determined by investigator assessment per participant based on their medical history and disease stage. Elevated GGT was any value greater than the upper limit of the standard reference range used by patient's laboratory. | Baseline; Month 3 |
| Count of Participants With Elevated ALT and/or GGT at Baseline and With Clinically Significant Improvement at Month 3 | Clinically significant improvement was determined by investigator assessment per participant based on their medical history and disease stage. Elevated ALT (and GGT) was any value greater than the upper limit of the standard reference range used by patient's laboratory. | Baseline; Month 3 |
| Count of Participants With Abnormal Magnetic Resonance Cholangiopancreatography (MRCP) Imaging at Baseline and With Clinically Significant Improvement at Year 1 | Clinically significant improvement was determined by investigator assessment per participant based on their medical history and disease stage. MRCP imaging was abnormal if it included biliary beading, biliary strictures, dilated bile duct, and/or liver fibrosis. | Baseline; Year 1 |
| Count of Participants With Abnormal Liver Biopsies at Baseline and With Clinically Significant Improvement at Year 1 |
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Inclusion Criteria:
PSC Diagnosis: Liver biopsy and/or imaging (MRCP, ERCP, CT, or US
Colonoscopy within 1 year or starting of study
2 groups:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Kenneth Cox, MD | Stanford University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Stanford University Medical Center | Palo Alto | California | 94304 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 23054338 | Result | Abarbanel DN, Seki SM, Davies Y, Marlen N, Benavides JA, Cox K, Nadeau KC, Cox KL. Immunomodulatory effect of vancomycin on Treg in pediatric inflammatory bowel disease and primary sclerosing cholangitis. J Clin Immunol. 2013 Feb;33(2):397-406. doi: 10.1007/s10875-012-9801-1. Epub 2012 Oct 9. | |
| 32633158 | Derived |
| Label | URL |
|---|---|
| Stanford Clinical Trials | View source |
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Two participants in the adult cohort completed the study but were not analyzed for outcomes (1 post-liver transplant patient; 1 completed the study but followed a diet that could influence results analysis). Two adult participants who consented but withdrew prior to treatment were not analyzed for outcomes.
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| ID | Title | Description |
|---|---|---|
| FG000 | Oral Vancomycin-Children | For children who weight < or = 30 kg, the vancomycin dose will be 50 mg/kg/day given orally 3 times per day for the 1st month and continue with the same dose for subsequent months if the clinical laboratory studies improved and are normal. If the laboratory studies are not normal the dose will be increased to 75 mg/kg/day given orally 3 times per day for the 2nd month and 100mg/kg/day given orally 3 times per day the 3rd month. If the laboratory studies do not improve by the end of the 3rd month since starting the vancomycin, the vancomycin will be stopped and the child will not continue the study. Oral Vancomycin |
| FG001 | Oral Vancomycin-Adults | For adults and children who weigh >30 kg, the vancomycin dose will be 500 mg given orally 3 times per day for the 1st month and continue with this dose if the clinical laboratory studies improve and are normal. If the laboratory studies are not normal the dose will be increased to 750 mg 3 times per day for the 2nd month and 1000 mg 3 times per day the 3rd month. Oral Vancomycin |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Participants who completed the protocol are included in the analysis
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| ID | Title | Description |
|---|---|---|
| BG000 | Oral Vancomycin-Children | For children who weight < or = 30 kg, the vancomycin dose will be 50 mg/kg/day given orally 3 times per day for the 1st month and continue with the same dose for subsequent months if the clinical laboratory studies improved and are normal. If the laboratory studies are not normal the dose will be increased to 75 mg/kg/day given orally 3 times per day for the 2nd month and 100mg/kg/day given orally 3 times per day the 3rd month. If the laboratory studies do not improve by the end of the 3rd month since starting the vancomycin, the vancomycin will be stopped and the child will not continue the study. Oral Vancomycin |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | 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 | Count of Participants With Elevated Alanine Aminotransferase (ALT) at Baseline and With Clinically Significant Improvement at Month 3 | Clinically significant improvement was determined by investigator assessment per participant based on their medical history and disease stage. Elevated ALT was any value greater than the upper limit of the standard reference range used by patient's laboratory. | Participants with ALT elevated at baseline are included in the analysis. | Posted | Count of Participants | Participants | Baseline; Month 3 |
|
Up to 2 years
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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 | Oral Vancomycin-Children | For children who weight < or = 30 kg, the vancomycin dose will be 50 mg/kg/day given orally 3 times per day for the 1st month and continue with the same dose for subsequent months if the clinical laboratory studies improved and are normal. If the laboratory studies are not normal the dose will be increased to 75 mg/kg/day given orally 3 times per day for the 2nd month and 100mg/kg/day given orally 3 times per day the 3rd month. If the laboratory studies do not improve by the end of the 3rd month since starting the vancomycin, the vancomycin will be stopped and the child will not continue the study. Oral Vancomycin |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Biliary stricture requiring stent | Hepatobiliary disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Kenneth Cox | Stanford University | (650) 723-5070 | KCox@stanfordchildrens.org |
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| ID | Term |
|---|---|
| D015209 | Cholangitis, Sclerosing |
| D001733 | Bites and Stings |
| ID | Term |
|---|---|
| D002761 | Cholangitis |
| D001649 | Bile Duct Diseases |
| D001660 | Biliary Tract Diseases |
| D004066 | Digestive System Diseases |
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| ID | Term |
|---|---|
| D014640 | Vancomycin |
| ID | Term |
|---|---|
| D006020 | Glycopeptides |
| D006001 | Glycoconjugates |
| D002241 | Carbohydrates |
| D010455 | Peptides |
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Clinically significant improvement was determined by investigator assessment per participant based on their medical history and disease stage. Liver pathology was considered abnormal if the biopsy was S1 or greater on the liver fibrosis staging scale (S0 no fibrosis, S1 mild fibrosis, S2 moderate fibrosis, S3 sever fibrosis, S4 cirrhosis). |
| Baseline; Year 1 |
| Count of Participants With Abnormal MRCP and/or Liver Biopsy at Baseline and With Clinically Significant Improvement at Year 1 | Clinically significant improvement was determined by investigator assessment per participant based on their medical history and disease stage. MRCP imaging was abnormal if it included biliary beading, biliary strictures, dilated bile duct, and/or liver fibrosis. Liver pathology was considered abnormal if the biopsy was S1 or greater on the liver fibrosis staging scale (S0 no fibrosis, S1 mild fibrosis, S2 moderate fibrosis, S3 sever fibrosis, S4 cirrhosis). | Baseline; Year 1 |
| Ali AH, Damman J, Shah SB, Davies Y, Hurwitz M, Stephen M, Lemos LM, Carey EJ, Lindor KD, Buness CW, Alrabadi L, Berquist WE, Cox KL. Open-label prospective therapeutic clinical trials: oral vancomycin in children and adults with primary sclerosing cholangitis. Scand J Gastroenterol. 2020 Aug;55(8):941-950. doi: 10.1080/00365521.2020.1787501. Epub 2020 Jul 7. |
| Withdrawal by Subject |
|
| Physician Decision |
|
| BG001 | Oral Vancomycin-Adults | For adults and children who weigh >30 kg, the vancomycin dose will be 500 mg given orally 3 times per day for the 1st month and continue with this dose if the clinical laboratory studies improve and are normal. If the laboratory studies are not normal the dose will be increased to 750 mg 3 times per day for the 2nd month and 1000 mg 3 times per day the 3rd month. Oral Vancomycin |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| OG001 | Oral Vancomycin-Adults | For adults and children who weigh >30 kg, the vancomycin dose will be 500 mg given orally 3 times per day for the 1st month and continue with this dose if the clinical laboratory studies improve and are normal. If the laboratory studies are not normal the dose will be increased to 750 mg 3 times per day for the 2nd month and 1000 mg 3 times per day the 3rd month. Oral Vancomycin |
|
|
| Primary | Count of Participants With Elevated Gamma-glutamyltransferase (GGT) at Baseline and With Clinically Significant Improvement at Month 3 | Clinically significant improvement was determined by investigator assessment per participant based on their medical history and disease stage. Elevated GGT was any value greater than the upper limit of the standard reference range used by patient's laboratory. | Participants with GGT elevated at baseline are included in the analysis. | Posted | Count of Participants | Participants | Baseline; Month 3 |
|
|
|
| Primary | Count of Participants With Elevated ALT and/or GGT at Baseline and With Clinically Significant Improvement at Month 3 | Clinically significant improvement was determined by investigator assessment per participant based on their medical history and disease stage. Elevated ALT (and GGT) was any value greater than the upper limit of the standard reference range used by patient's laboratory. | Participants with ALT and/or GGT elevated at baseline are included in the analysis. | Posted | Count of Participants | Participants | Baseline; Month 3 |
|
|
|
| Primary | Count of Participants With Abnormal Magnetic Resonance Cholangiopancreatography (MRCP) Imaging at Baseline and With Clinically Significant Improvement at Year 1 | Clinically significant improvement was determined by investigator assessment per participant based on their medical history and disease stage. MRCP imaging was abnormal if it included biliary beading, biliary strictures, dilated bile duct, and/or liver fibrosis. | Participants with abnormal MRCP at baseline are included in the analysis. | Posted | Count of Participants | Participants | Baseline; Year 1 |
|
|
|
| Primary | Count of Participants With Abnormal Liver Biopsies at Baseline and With Clinically Significant Improvement at Year 1 | Clinically significant improvement was determined by investigator assessment per participant based on their medical history and disease stage. Liver pathology was considered abnormal if the biopsy was S1 or greater on the liver fibrosis staging scale (S0 no fibrosis, S1 mild fibrosis, S2 moderate fibrosis, S3 sever fibrosis, S4 cirrhosis). | Participants with abnormal liver biopsy at baseline and who had a post-treatment liver biopsy are included in the analysis. | Posted | Count of Participants | Participants | Baseline; Year 1 |
|
|
|
| Primary | Count of Participants With Abnormal MRCP and/or Liver Biopsy at Baseline and With Clinically Significant Improvement at Year 1 | Clinically significant improvement was determined by investigator assessment per participant based on their medical history and disease stage. MRCP imaging was abnormal if it included biliary beading, biliary strictures, dilated bile duct, and/or liver fibrosis. Liver pathology was considered abnormal if the biopsy was S1 or greater on the liver fibrosis staging scale (S0 no fibrosis, S1 mild fibrosis, S2 moderate fibrosis, S3 sever fibrosis, S4 cirrhosis). | Participants with abnormal MRCP and/or liver biopsy at baseline are included in the analysis. | Posted | Count of Participants | Participants | Baseline; Year 1 |
|
|
|
| 0 |
| 14 |
| 1 |
| 14 |
| 0 |
| 14 |
| EG001 | Oral Vancomycin-Adults | For adults and children who weigh >30 kg, the vancomycin dose will be 500 mg given orally 3 times per day for the 1st month and continue with this dose if the clinical laboratory studies improve and are normal. If the laboratory studies are not normal the dose will be increased to 750 mg 3 times per day for the 2nd month and 1000 mg 3 times per day the 3rd month. Oral Vancomycin | 0 | 20 | 0 | 20 | 0 | 20 |
| Progression of PSC | Hepatobiliary disorders | Systematic Assessment |
|
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| D011041 |
| Poisoning |
| D064419 | Chemically-Induced Disorders |
| D014947 | Wounds and Injuries |
| D000602 |
| Amino Acids, Peptides, and Proteins |