Understanding the causes of primary sclerosing cholangitis

Unraveling the Mechanisms Underlying Primary Sclerosing Cholangitis Through a Multidisciplinary, Integrative Research Approach

This study looks at the causes of primary sclerosing cholangitis by collecting health information and samples from people with the disease to see what genetic and immune factors might be involved.

Quick facts

• Study type: Observational
• Enrollment: 143 (estimated)
• Ages: 18 Years to 90 Years
• Sex: All
• Sponsor: National Institutes of Health Clinical Center (CC) (NIH)
• Locations: 1 site (Bethesda, Maryland)
• Trial ID: NCT04685200 on ClinicalTrials.gov

What this trial studies

This observational study aims to investigate the biological mechanisms underlying primary sclerosing cholangitis (PSC), a rare chronic liver disease. Researchers will collect comprehensive data through medical history, physical exams, and various biological samples, including blood, saliva, urine, and stool. Participants will undergo procedures such as colonoscopy and upper endoscopy to gather detailed information on immune responses and microbiome signatures. The goal is to identify genetic and immune factors that contribute to the disease's development and progression.

Who should consider this trial

Good fit: Ideal candidates for this study are adults aged 18 and older who have been diagnosed with primary sclerosing cholangitis.

Not a fit: Patients with chronic liver diseases other than PSC or those who have undergone liver transplantation may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to improved understanding and management of primary sclerosing cholangitis, potentially enhancing patient outcomes.

How similar studies have performed: While the approach is comprehensive, similar studies have shown promise in understanding chronic liver diseases, but this specific integrative methodology is relatively novel.

Eligibility criteria

* PSC SUBJECTS:

INCLUSION CRITERIA:

In order to be eligible to participate in this study, an individual must meet all of the following criteria:

1. Stated willingness to comply with all study procedures and availability for the duration of the study
2. Male or nonpregnant female, greater than or equal to 18 years of age
3. Evidence of PSC established by biochemical testing and either MRCP or ERCP. Participant must have evidence of large duct disease on imaging.
4. Agreement to adhere to Lifestyle Considerations throughout study duration.

EXCLUSION CRITERIA:

An individual who meets any of the following criteria will be excluded from participation in this study:

1. Pregnant or lactating women or females of child-bearing age not taking measures to prevent pregnancy during the period of study.
2. History of clinical, serologic, or histopathologic evidence supporting etiologies of chronic liver disease other than PSC
3. History of liver transplantation
4. Diagnosis consistent with secondary sclerosing cholangitis (cholelithiasis, bile duct strictures secondary to ischemia, HIV cholangiopathy, etc.).
5. Current or past clinical evidence of decompensated liver disease (e.g. ascites, bleeding esophageal varices, spontaneous bacterial peritonitis, encephalopathy, etc.).
6. History of liver or bile duct lesions concerning for malignancy.
7. Ca-19-9 \>130 U/microL
8. Alpha-fetoprotein level greater than 200 ng/microL.
9. Patients with active bacterial, viral, or fungal, systemic or localized infection.
10. Unwillingness to refrain from ingesting probiotics during study.
11. History of systemic disease not related to PSC that is poorly controlled or associated with declining functional status. Examples include but are not limited to: poorly controlled diabetes mellitus, chronic renal failure with eGFR is \<60 microl/min/1.73m\^2, chronic

    symptomatic heart failure or severe COPD.
12. Patients with history of any gastrointestinal malignancy in the last 3 years prior to enrollment will be excluded. Patients with history of any malignancy in the last 3 years prior to enrollment other than those individuals who had undergone curative surgical therapy and deemed as low risk for recurrence by her/his treating physician would be excluded.
13. History of portal vein thrombosis
14. Patients with severe allergic reactions to iodine or other contrast, which cannot be controlled by premedication with antihistamines or steroids.
15. History of gastric and/or proximal small bowel surgery including bariatric surgery such as Roux-en-Y gastric bypass
16. Contraindication to monitored anesthesia care and/or medications that are commonly used for conscious sedation during GI Endoscopy
17. Use of anti-coagulant and anti-platelet agents excluding aspirin and NSAIDs
18. Contraindications to completing MRCP or MRI
19. Absolute neutrophil count below 1000/mm\^3
20. Hemoglobin level below 10.0 g/dl
21. Platelet count lower than 50,000/mm\^3.
22. INR greater than or equal to 1.5, PTT greater thna or equal to 1.3 times control and/or any known history of disease associated with

    increased bleeding diathesis.
23. Inability to provide informed consent

CONTROLS:

INCLUSION CRITERIA:

In order to be eligible to participate in this study, an individual must meet all of the following criteria:

1. Male or female greater than or equal to 18 years of age
2. Any individual who is either a parent, sibling or child of a PSC patient enrolled to the study, or an unrelated person who has been living with the patient for at least 3 consecutive months before study enrollment

EXCLUSION CRITERIA:

An individual who meets any of the following criteria will be excluded from participation in this study:

1. History suggestive of PSC
2. History of chronic liver disease (except for steatosis)
3. Patients with history of any malignancy in the last 3 years prior to enrollment other than those individuals who had undergone curative surgical therapy and deemed as low risk for recurrence by her/his treating physician would be excluded.
4. History of Inflammatory Bowel Disease
5. Antibiotic use within the last 6 weeks
6. Pregnancy
7. Inability to provide informed consent

Where this trial is running

Bethesda, Maryland

• National Institutes of Health Clinical Center — Bethesda, Maryland, United States (Recruiting)

Study contacts

• Principal investigator: Theo Heller, M.D. — National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Study coordinator: Alaina K Magnani

Conditions Primary Sclerosing Cholangitis; Inflammatory Bowel Disease; Liver Disease; Natural History