Gluten-free Diet in PSC and IBD

Study Overview
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Brief Summary
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Primary sclerosing cholangitis (PSC) is a progressive disease of the biliary tree, which represents one of the most frequent indications for orthotopic liver transplantation (OLTx) in developed countries. There are several lines of evidence that dietary gluten/gliadin displays chronic pro-inflammatory, LPS-like properties. Recent evidence demonstrated the protective effect of gluten- free diet (GFD) in autoimmune diseases like type 1 diabetes, irritable bowel syndrome, non-celiac gluten sensitivity and some neurological disorders. This study is intended to explore therapeutic effect of GFD on PSC and IBD in prospective self-controlled mono-centric intervention study. Hypothesis: Avoidance of gluten in diet will reduce progression, symptoms and intestinal inflammation in PSC and UC patients.

Official Title
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Effect of Gluten-free Diet on Clinical Symptoms, Immune Response and Microbiome in Primary Sclerosing Cholangitis and Inflammatory Bowel Disease

Conditions
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Primary Sclerosing Cholangitis, Ulcerative Colitis, Biliary Tract Diseases, Biliary Disease Tract, Intestinal Disease

Intervention / Treatment
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* Dietary Supplement: Gluten-free diet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria (for PSC group): Established diagnosis of PSC (based on radiologic features, typical finding on MRCP or ERCP) Age 18 - 65 years ALP 1,5x higher than ULN Signed informed consent Exclusion Criteria (for PSC group): Patients on gluten-free diet Patients with coeliac disease or wheat allergy Liver transplant recipients PSC/AIH overlap syndrome Other causes of liver disease Radiologic or clinical signs of decompensated liver cirrhosis Advanced liver cirrhosis (MELD score ˃ 15) Recurrent acute cholangitis or cholangiogenic sepsis in past 3 months Use of antibiotics in past 3 months History of malignancy Pregnant women Not signed informed consent Inclusion criteria (for UC group): Ulcerative colitis diagnosed based on clinical, endoscopic and histological findings Extension of affected colon > 15cm Mayo score 0-4 Signed informed consent Exclusion criteria (for UC group): CMV, Clostridium difficile enterocolitis in past 3 months Use of antibiotics in past 3 months Patients with coeliac disease or wheat allergy Patients on gluten-free diet Pregnant women Not signed informed consent Biologic therapy Methotrexate Prednison > 10 mg Not signed informed consent

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Prospective, self-controlled pilot clinical trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Primary sclerosing cholangitis<br> | Dietary Supplement: Gluten-free diet<br>* After initial fase of habitual diet (6 months), patients will start Gluten-free diet for a period of 12 months<br>|
| Experimental: Ulcerative Colitis<br> | Dietary Supplement: Gluten-free diet<br>* After initial fase of habitual diet (6 months), patients will start Gluten-free diet for a period of 12 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Decrease of laboratory markers of cholestasis | Change of alkaline phosphatase > 25% or normalisation. | 6-12 months | 
| Changes of intestinal microbiome composition. | 16S-rRNA sequencing | 6-12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes of morphological signs of intestinal inflammation | Endoscopic Mayo score (Grade 0 - normal or inactive disease; Grade 1 - mild disease acitivity; Grade 2 - moderate disease acitivity; Grade 3 - Severe disease acitivity) | 6-12 months | 
| Improvement of quality of life and symptoms of ulcerative colitis. | UC Quality of life questionnaire (The Short Inflammatory Bowel Disease) Questionnaire) | 6-12 months | 
| Improvement of quality of life and symptoms of primary sclerosing cholangitis | PSC quality of life questionnaire (PSC PRO) | 6-12 months | 
| Changes of histopathological signs of intestinal inflammation | Nancy histological index (Grade 0 - no histological significant disease; Grade 1 - chronic inflammatory infiltrate with no acute inflammatory infiltrate; Grade 2 - Mildly active disease, Grade 3 - Moderately active disease; Grade 4 - Severly active disease) | 6-12 months | 
| Change from baseline of liver stiffness. | Shear-wave elastography (F0-F4) | 6-12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Primary sclerosing cholangitis, Cholangitis, Gluten-free diet, Ulcerative Colitis, Microbiome