Primary Sclerosing Cholangitis
Conditions
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).
Interventions
DRUGCurcumin
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.
Sponsors
EuroPharma, Inc.
John E. Eaton
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Serum Alkaline Phosphatase (SAP) | baseline, 12 weeks | 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
| Measure | Time frame | Description |
|---|---|---|
| Change in Total Bilirubin | Baseline, 12 weeks | 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) | Baseline, 12 weeks | 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 Serum Aspartate Aminotransferase (AST) | Baseline, 12 weeks | 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 Fatigue Severity | Baseline, 12 weeks | 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 | Baseline, 12 weeks | 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) |
| Change in Mayo Primary Sclerosing Cholangitis (PSC) Risk Score | Baseline, 12 weeks | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Curcumin 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.
Curcumin: 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. | 15 |
| Total | 15 |
Baseline characteristics
| Characteristic | Curcumin | — |
|---|---|---|
| Age, Continuous | 46 years | — |
| Inflammatory Bowel Disease Present | 10 Participants | — |
| Primary Sclerosing Cholangitis Duration | 9.00 years | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Region of Enrollment United States | 15 participants | — |
| Sex: Female, Male Female | 8 Participants | — |
| Sex: Female, Male Male | 7 Participants | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 15 |
| other Total, other adverse events | 3 / 15 |
| serious Total, serious adverse events | 0 / 15 |
Outcome results
Primary
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.
Time frame: baseline, 12 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Curcumin | Change in Serum Alkaline Phosphatase (SAP) | 3 Participants |
p-value: 0.03t-test, 2 sided
Secondary
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)
Time frame: Baseline, 12 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Curcumin | Change in C-Reactive Protein (CRP) | 3.4 mg/L |
p-value: 0.41t-test, 2 sided
Secondary
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.
Time frame: Baseline, 12 weeks
Population: Twelve subjects completed questionnaires. Three subjects did not complete questionnaires.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Curcumin | Change in Fatigue Severity | 8.00 score on a scale |
p-value: 0.06t-test, 2 sided
Secondary
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.
Time frame: Baseline, 12 weeks
Population: Twelve subjects completed questionnaires. Three subjects did not complete questionnaires
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Curcumin | Change in Mayo Primary Sclerosing Cholangitis (PSC) Risk Score | 0.54 score on a scale |
p-value: 0.15t-test, 2 sided
Secondary
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)
Time frame: Baseline, 12 weeks
Population: Twelve of the subjects completed questionnaires. Three subjects did not complete questionnaires
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Curcumin | Change in Pruritus | 8.00 score on a scale |
p-value: 0.93t-test, 2 sided
Secondary
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)
Time frame: Baseline, 12 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Curcumin | Change in Serum Aspartate Aminotransferase (AST) | 78 U/L |
p-value: 0.59t-test, 2 sided
Secondary
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)
Time frame: Baseline, 12 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Curcumin | Change in Total Bilirubin | 0.6 mg/dL |
p-value: 0.91t-test, 2 sided