A Study Evaluating the Safety and Efficacy of Curcumin in Patients With Primary Sclerosing Cholangitis (PSC)

Primary Sclerosing Cholangitis Clinical Trial

Official title:

An Open-Label Pilot Study Evaluating the Safety and Efficacy of Curcumin in Patients With Primary Sclerosing Cholangitis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02978339
• Other study ID #: 14-002660
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: June 9, 2017
• Est. completion date: January 8, 2019

Study information

• Verified date: January 2020
• Source: Mayo Clinic
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: January 8, 2019
• Est. primary completion date: November 16, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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, a1-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.

Related Conditions & MeSH terms

• Cholangitis
• Cholangitis, Sclerosing
• Primary Sclerosing Cholangitis

Intervention

Drug:
• 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.

Locations

Country	Name	City	State
United States	Mayo Clinic	Rochester	Minnesota

Sponsors (2)

Lead Sponsor	Collaborator
John E. Eaton	EuroPharma, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	baseline, 12 weeks
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)	Baseline, 12 weeks
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)	Baseline, 12 weeks
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)	Baseline, 12 weeks
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.	Baseline, 12 weeks
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.	Baseline, 12 weeks
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)	Baseline, 12 weeks

External Links

•   Mayo Clinic Clinical Trials
•   Scandinavian Journal of Gastroenterology