Back to resultsA Study Evaluating the Safety and Efficacy of Curcumin in Patients With Primary Sclerosing Cholangitis (PSC)
Primary Purpose
Primary Sclerosing Cholangitis
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Curcumin
Sponsored by
About this trial
This is an interventional treatment trial for Primary Sclerosing Cholangitis
Eligibility Criteria
Inclusion Criteria:
Diagnosis of primary sclerosing cholangitis (PSC) established by all of the following criteria:
- Alkaline phosphatase >1.5x upper limit of normal for at least 6 months prior to study enrollment
- Cholangiography demonstrating intrahepatic and/or extrahepatic biliary dilation, beading, and/or strictures consistent with PSC
- Liver histology (if available for review) consistent with or diagnostic of PSC
- Women of child-bearing potential willing to use birth control for the duration of the study.
Exclusion Criteria:
- Treatment with any investigational agents within three months prior to or during the study
- Treatment with systemic antibiotics, azulfidine, systemic corticosteroids, colchicine, methotrexate, azathioprine, cyclosporine, chlorambucil, budesonide, pentoxifylline, tacrolimus, or vitamin E within three months prior to or during the study.
- Concomitant treatment with NSAIDS, antiplatelet agents, antihyperlipidemics, and anticoagulant warfarin.
- Anticipated need for liver transplant within one year as determined by Mayo PSC risk score (<80% one-year survival without transplant)
- Active drug or alcohol use
- Findings suggestive of liver disease of an alternative or concomitant etiology, such as chronic alcoholic liver disease, chronic hepatitis B or C infection, hemochromatosis, Wilson's disease, α1-antitrypsin deficiency, non-alcoholic steatohepatitis, primary biliary cirrhosis, or secondary sclerosing cholangitis (e.g., post-liver transplantation biliary stricture)
- Pregnancy or lactation
- Any condition that, in the opinion of the investigator, would interfere with the patient's ability to complete the study safely or successfully.
Sites / Locations
- Mayo Clinic
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Curcumin
Arm Description
Subjects will receive one 750 mg softgel by mouth twice a day for 12 weeks. Each each 750 mg CuraMed® softgel supplies 500 mg of highly bioavailable BCM-95 curcumin.
Outcomes
Primary Outcome Measures
Change in Serum Alkaline Phosphatase (SAP)
Number of subjects who experience a reduction of Serum Alkaline Phosphatase (SAP) to less than 1.5 x Upper Limit of Normal or a 40% reduction between baseline and week 12.
Secondary Outcome Measures
Change in Serum Aspartate Aminotransferase (AST)
AST is an enzyme found in high amounts in liver, heart, and muscle cells. This test is mainly done along with other tests such as alkaline phosphatase and bilirubin to diagnose and monitor liver disease. This test evaluates hepatocyte integrity, as serum levels of this enzyme rise in response to a variety of forms of injury to hepatic cells. The normal range is 10 to 40 Unit/Liter (U/L)
Change in Total Bilirubin
Bilirubin is a yellowish pigment found in bile, a fluid made by the liver. A small amount of older red blood cells are replaced by new blood cells every day. Bilirubin is left after these older blood cells are removed. The liver helps break down bilirubin so that it can be removed from the body in the stool. The normal range for total bilirubin is 0.3 to 1.9 milligrams/deciliter (mg/dL)
Change in C-Reactive Protein (CRP)
C-reactive protein is a substance produced by the liver in response to inflammation. Normal CRP levels are below 3.0 milligrams/Liter (mg/L)
Change in Mayo Primary Sclerosing Cholangitis (PSC) Risk Score
The Mayo Risk Score (R) = (0.0295 * (age in years)) + (0.5373 * natural logarithm(total bilirubin in mg/dL)) - (0.8389 * (serum albumin in g/dL)) + (0.5380 * natural logarithm(AST in IU/L) + (1.2426 * (points for variceal bleeding)) where:
AST = serum aspartate aminotransferase level, Points for variceal bleeding: 0 if none, 1 if present. Each unit increase in the Mayo Risk Score (R) is associated with a 2.5-fold increase in the risk of death. Most references to the score round the coefficients to 2 decimal places. The score shows very slight upward slope over time in stable patients, but during the terminal phase it shows an acceleration in progression.
Change in Fatigue Severity
Fatigue will be measured by a Modified Fatigue Impact Scale (MFIS). This instrument provides an assessment of the effects of fatigue in terms of physical, cognitive, and psychosocial functioning. The full-length MFIS consists of 21 items. Subjects rate on a 5-point scale with 0 = never to 4 = almost always. The total score for the MFIS is the sum of the scores for the 21 items ranging from score of 0-84. Higher numbers indicate greater fatigue.
Change in Pruritus
Pruritus will be measured by the 5-D itch Scale. The 5-D itch scale was developed as a brief but multidimensional questionnaire designed to be useful as an outcome measure in clinical trials." The five dimensions are degree, duration, direction, disability and distribution. The duration, degree and direction domains each include one item, while the disability domain has four items. All items of the first four domains were measured on a five-point Likert scale (1 = Not present/resolved/never, 5 = Unbearable/getting worse/always).The distribution domain included 16 potential locations of itch, including 15 body part items and one point of contact with clothing or bandages.The scores of each of the five domains are achieved separately and then summed together to obtain a total 5-D score. 5-D scores can potentially range between 5 (no pruritus) and 25 (most severe pruritus)
Full Information
NCT ID
NCT02978339
First Posted
November 22, 2016
Last Updated
January 7, 2020
Sponsor
John E. Eaton
Collaborators
EuroPharma, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT02978339
Brief Title
A Study Evaluating the Safety and Efficacy of Curcumin in Patients With Primary Sclerosing Cholangitis (PSC)
Official Title
An Open-Label Pilot Study Evaluating the Safety and Efficacy of Curcumin in Patients With Primary Sclerosing Cholangitis
Study Type
Interventional
2. Study Status
Record Verification Date
January 2020
Overall Recruitment Status
Completed
Study Start Date
June 9, 2017 (Actual)
Primary Completion Date
November 16, 2018 (Actual)
Study Completion Date
January 8, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
John E. Eaton
Collaborators
EuroPharma, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study is to determine whether curcumin, a drug and naturally-occurring plant compound, is safe and effective in the treatment of primary sclerosing cholangitis (PSC).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Primary Sclerosing Cholangitis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
15 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Curcumin
Arm Type
Experimental
Arm Description
Subjects will receive one 750 mg softgel by mouth twice a day for 12 weeks. Each each 750 mg CuraMed® softgel supplies 500 mg of highly bioavailable BCM-95 curcumin.
Intervention Type
Drug
Intervention Name(s)
Curcumin
Other Intervention Name(s)
CuraMed® softgel
Intervention Description
Subjects will receive one 750 mg softgel by mouth twice a day for 12 weeks. Each each 750 mg CuraMed® softgel supplies 500 mg of highly bioavailable BCM-95 curcumin.
Primary Outcome Measure Information:
Title
Change in Serum Alkaline Phosphatase (SAP)
Description
Number of subjects who experience a reduction of Serum Alkaline Phosphatase (SAP) to less than 1.5 x Upper Limit of Normal or a 40% reduction between baseline and week 12.
Time Frame
baseline, 12 weeks
Secondary Outcome Measure Information:
Title
Change in Serum Aspartate Aminotransferase (AST)
Description
AST is an enzyme found in high amounts in liver, heart, and muscle cells. This test is mainly done along with other tests such as alkaline phosphatase and bilirubin to diagnose and monitor liver disease. This test evaluates hepatocyte integrity, as serum levels of this enzyme rise in response to a variety of forms of injury to hepatic cells. The normal range is 10 to 40 Unit/Liter (U/L)
Time Frame
Baseline, 12 weeks
Title
Change in Total Bilirubin
Description
Bilirubin is a yellowish pigment found in bile, a fluid made by the liver. A small amount of older red blood cells are replaced by new blood cells every day. Bilirubin is left after these older blood cells are removed. The liver helps break down bilirubin so that it can be removed from the body in the stool. The normal range for total bilirubin is 0.3 to 1.9 milligrams/deciliter (mg/dL)
Time Frame
Baseline, 12 weeks
Title
Change in C-Reactive Protein (CRP)
Description
C-reactive protein is a substance produced by the liver in response to inflammation. Normal CRP levels are below 3.0 milligrams/Liter (mg/L)
Time Frame
Baseline, 12 weeks
Title
Change in Mayo Primary Sclerosing Cholangitis (PSC) Risk Score
Description
The Mayo Risk Score (R) = (0.0295 * (age in years)) + (0.5373 * natural logarithm(total bilirubin in mg/dL)) - (0.8389 * (serum albumin in g/dL)) + (0.5380 * natural logarithm(AST in IU/L) + (1.2426 * (points for variceal bleeding)) where:
AST = serum aspartate aminotransferase level, Points for variceal bleeding: 0 if none, 1 if present. Each unit increase in the Mayo Risk Score (R) is associated with a 2.5-fold increase in the risk of death. Most references to the score round the coefficients to 2 decimal places. The score shows very slight upward slope over time in stable patients, but during the terminal phase it shows an acceleration in progression.
Time Frame
Baseline, 12 weeks
Title
Change in Fatigue Severity
Description
Fatigue will be measured by a Modified Fatigue Impact Scale (MFIS). This instrument provides an assessment of the effects of fatigue in terms of physical, cognitive, and psychosocial functioning. The full-length MFIS consists of 21 items. Subjects rate on a 5-point scale with 0 = never to 4 = almost always. The total score for the MFIS is the sum of the scores for the 21 items ranging from score of 0-84. Higher numbers indicate greater fatigue.
Time Frame
Baseline, 12 weeks
Title
Change in Pruritus
Description
Pruritus will be measured by the 5-D itch Scale. The 5-D itch scale was developed as a brief but multidimensional questionnaire designed to be useful as an outcome measure in clinical trials." The five dimensions are degree, duration, direction, disability and distribution. The duration, degree and direction domains each include one item, while the disability domain has four items. All items of the first four domains were measured on a five-point Likert scale (1 = Not present/resolved/never, 5 = Unbearable/getting worse/always).The distribution domain included 16 potential locations of itch, including 15 body part items and one point of contact with clothing or bandages.The scores of each of the five domains are achieved separately and then summed together to obtain a total 5-D score. 5-D scores can potentially range between 5 (no pruritus) and 25 (most severe pruritus)
Time Frame
Baseline, 12 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Diagnosis of primary sclerosing cholangitis (PSC) established by all of the following criteria:
Alkaline phosphatase >1.5x upper limit of normal for at least 6 months prior to study enrollment
Cholangiography demonstrating intrahepatic and/or extrahepatic biliary dilation, beading, and/or strictures consistent with PSC
Liver histology (if available for review) consistent with or diagnostic of PSC
Women of child-bearing potential willing to use birth control for the duration of the study.
Exclusion Criteria:
Treatment with any investigational agents within three months prior to or during the study
Treatment with systemic antibiotics, azulfidine, systemic corticosteroids, colchicine, methotrexate, azathioprine, cyclosporine, chlorambucil, budesonide, pentoxifylline, tacrolimus, or vitamin E within three months prior to or during the study.
Concomitant treatment with NSAIDS, antiplatelet agents, antihyperlipidemics, and anticoagulant warfarin.
Anticipated need for liver transplant within one year as determined by Mayo PSC risk score (<80% one-year survival without transplant)
Active drug or alcohol use
Findings suggestive of liver disease of an alternative or concomitant etiology, such as chronic alcoholic liver disease, chronic hepatitis B or C infection, hemochromatosis, Wilson's disease, α1-antitrypsin deficiency, non-alcoholic steatohepatitis, primary biliary cirrhosis, or secondary sclerosing cholangitis (e.g., post-liver transplantation biliary stricture)
Pregnancy or lactation
Any condition that, in the opinion of the investigator, would interfere with the patient's ability to complete the study safely or successfully.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Nicholas F LaRusso, M.D.
Organizational Affiliation
Mayo Clinic
Official's Role
Principal Investigator
Facility Information:
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905-0001
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Links:
URL
https://www.mayo.edu/research/clinical-trials
Description
Mayo Clinic Clinical Trials
Learn more about this trial
A Study Evaluating the Safety and Efficacy of Curcumin in Patients With Primary Sclerosing Cholangitis (PSC)
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