Clinical Research Directory

Changes in Bile Acids and Microbiota in Patients With Hepatitis D Treated With Bulvertide

HDV is an RNA virus that infects only in the presence of HBV, affecting about 13% of HBsAg carriers. In Italy, prevalence ranges from 3.2% to 9.3%. It increases the risk of cirrhosis, fulminant hepatitis, and HCC, particularly in high-risk groups (HIV, HCV, drug users, dialysis patients). Until 2020, pegIFN was the only therapy; since 2022, bulevirtide (BLV) has been available, blocking viral entry into hepatocytes and reducing HDV RNA and liver stiffness, with efficacy in 45-48% of patients, though the optimal treatment duration remains uncertain. The gut microbiota and bile acids also play a role in fibrosis and cirrhosis progression: dysbiosis, typical in cirrhotic patients, alters bile acid metabolism and increases intrahepatic toxicity.

Probiotic in Patients With Bile Acid Malabsorption/Diarrhea

The purpose of this study is to assess effect of the DSF probiotic on fecal bile acid levels in patients with BAM.

Magnesium in Gastrointestinal Disease

Individuals with gastrointestinal diseases - such as Crohn's disease, ulcerative colitis, ileostomy, or bile acid diarrhoea - are at increased risk of magnesium deficiency. Magnesium is a vital mineral that supports many essential functions in the body, including muscle contraction, nerve signalling, heart rhythm, and bone health. Deficiency may contribute to fatigue, muscle cramps, abnormal heart rhythms, and reduce the quality of life. The purpose of this study is to investigate the prevalence of magnesium deficiency in individuals with these conditions and to identify the most accurate and practical methods for assessing magnesium status in clinical care. Although plasma magnesium is commonly used in routine blood tests, it represents only about 1% of the body's total magnesium and may not reflect true magnesium levels within cells or tissues. Hence, this study compares several different ways of measuring magnesium, including: * Plasma magnesium * Magnesium levels in red and white blood cells (PBMC, RBC, and buffy coat) * Magnesium levels in muscle tissue (via biopsy) * A magnesium retention test, based on how much magnesium is excreted after an infusion The study includes four groups: 1. Patients with inflammatory bowel disease. 2. Patients with an ileostomy. 3. Patients with bile acid diarrhoea. 4. Healthy individuals (control group). All participants will provide blood and urine samples, and some may undergo optional biopsies of muscle or intestinal tissue. Participants will also complete questionnaires and undergo tests of muscle strength and body composition. The findings are expected to enhance the understanding and detection of magnesium deficiency in patients with gastrointestinal diseases and to aid in the development of more effective tools for identifying and treating this common yet often overlooked condition.

Treatment of Bile Acid Diarrhoea With Atorvastatin

Bile acid diarrhoea (BAD) is a socially debilitating disease with stomach pain, high stool frequency, urgency, and faecal incontinence as the main symptoms. Studies estimate that 1-2% of the population suffers from the disease. There is an unmet need for more treatment options in patients suffering from BAD. The investigators hypothesise that atorvastatin treatment lowers bile acid synthesis in patients with bile acid diarrhoea. The investigators will investigate this hypothesis in the current study, BASTA, which is a Randomised, Double-Blind, Placebo-Controlled, Crossover, Proof of Concept, Investigator-Initiated, Trial.

Bile Acids and Microbiome in Early Colorectal Carcinogenesis

Currently colorectal cancer pathogenesis is mainly explained by the adenoma-carcinoma sequence theory that was proposed more than half a century ago. It mainly focuses on the explanation of genetic mutations that develop throughout the disease course. However, several studies argue that there are also noticeable bile acid metabolism changes and microbiome composition changes within in colorectal cancer patients. However, carcinoma is the final step in the sequence, and prior steps are noticeably less well studied. Thus, the investigators hypothesize, that changes within microbiome and the changes in the urine, serum and gut bile acid composition further leads to the development of colorectal adenoma and subsequent invasive carcinoma. Adult participants (15 per group) referred for colonoscopy and histologically diagnosed with small (\<1cm) adenomas, large (\>1cm) adenomas, invasive CRC will be included in the study, as well as 15 healthy controls. Fecal samples will be collected from all participants before bowel preparation. Additionally, urine and serum samples will be collected. Participants will undergo polypectomy, endoscopic mucosal resections, depending on the location, size and histology of the polyp found. During colonoscopy the mucosal biopsy specimens from the lesion and from the healthy bowel -terminal ileum, and colon will be obtained using sterile biopsy forceps. The collected samples will be stored for bile acid and microbiome analysis and for possible further pathology and genetic testing. Healthy participants without visible colorectum pathology during colonoscopy will undergo colon and terminal ileum mucosal sampling. The investigators plan to evaluate the correlation between the urine and gut microbiome changes and bile acid composition and concentration in adenoma-carcinoma sequence and possibly determine novel bile acids. In addition, fecal, urine and tissue samples will be explored for gut microbiota and bile acid composition changes in healthy and along the adenoma-carcinoma sequence, with the possibility to propose a diagnostic test.