Oxylipins and lipoxygenases in cholestatic itch
- Conditions
- cholestatic itchcholestatic pruritus10019654
- Registration Number
- NL-OMON50822
- Lead Sponsor
- Academisch Medisch Centrum
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 220
In order to be eligible to participate in this study, a subject should:
1. Be able to provide informed consent
2. Meet the criteria of one of the following subgroups:
a) Patients of >=18 years of age who are diagnosed with non-hereditary
hepatobiliary diseases leading to cholestasis e.g.:
Primary sclerosing cholangitis (PSC)
• Based on: elevated serum alkaline phosphatase and *GT and characteristic
lesions on ERCP and/or magnetic resonance cholangiopancreaticography (MRCP)
Primary biliary cholangitis (PBC)
• Based on >=2 of 3 criteria: history of elevated alkaline phosphatase for at
least 6 months, liver biopsy consistent with PBC, positive anti-mitochondrial
antibody titer (or when low in titer anti-GP210 and/or anti-SP100 and/or
anti-PDC-E2 antibodies)
Malignant cholestatic diseases (e.g. cholangiocarcinoma)
• Based on the criteria of the subdiagnosis.
b) Patients prone to hereditary cholestatic diseases (patients of < 18 years of
age are exempted from punch biopsies):
Progressive familial intrahepatic cholestasis (PFIC)
• Based on: confirmed mutations in the ATP8B1, ABCB11 or ABCB4 genes.
Alagille syndrome
• Based on: confirmed mutations in the JAG1 or NOTCH2 genes.
c) Patients of >=18 years of age who are prone to intrahepatic cholestasis of
pregnancy (ICP).
• Based on: pruritus in pregnancy, elevated serum ALT activities and fasting
bile acid levels, and exclusion of other causes of liver dysfunction or
itching. Serum liver tests and fasted bile acids should normalize after
pregnancy.
Subjects who could be considered as a vulnerable population will be excluded
from participation in this study:
1. Clinically unstable subjects (as assessed by their treating physician)
2. Subjects with a confirmed infection
3. Subjects with a dermatologic disease other than the skin phenotype
associated with cholestasis
4. Subjects admitted to the ICU
5. Subjects experiencing itch as a result of cholestasis for less than three
months
6. Subject who are prone to another hepatic disease
Study & Design
- Study Type
- Observational invasive
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>To assess oxylipin levels in itching cholestatic patients and compare the<br /><br>levels of these compounds with non-itching cholestatic patients and healthy<br /><br>controls.</p><br>
- Secondary Outcome Measures
Name Time Method <p>Secondly, to investigate the association of itch and elevated levels of<br /><br>oxylipins (OXLAMs, OXAAMs) in serum and skin in different subgroups.<br /><br>Thirdly, to asses if lipoxygenases are expressed in elevated levels, and<br /><br>thereby are the main source of oxylipins in patients with cholestatic itch.<br /><br>Fourthly, to evaluate the effect of known therapies for cholestatic itch on<br /><br>lipoxygenase expression and oxylipin levels.<br /><br>Fifthly, to determine the tissue of origin of these oxylipins (skin and/or<br /><br>leukocytes)<br /><br>Lastly, we want to identify the lipoxygenase(s) responsible for the production<br /><br>of pruritogenic oxylipins found in itching cholestatic patients.</p><br>