Serum Metabolics-based Method for Diagnosing Bile Acid Diarrhoea

NCT ID: NCT06548009

Last Updated: 2025-05-01

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 150 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2024-05-31
• Study Completion Date: 2025-04-15

Brief Summary

Bile acid diarrhoea (BAD) is a common yet under-diagnosed and under-recognised disease. The primary symptoms are watery diarrhoea with high frequency of unpredictable bowel movements,urgency and faecal incontinence making BAD a debilitating condition. One of the challenges of BAD is the lack of a readily available and accurate diagnostic test.

The aim of this study is to validate a BAD diagnostic score (BDS) based on metabolomics.

Detailed Description

Bile acid diarrhoea (BAD) is a common yet under-diagnosed and under-recognised disease. The primary symptoms are watery diarrhoea with high frequency of unpredictable bowel movements,urgency and faecal incontinence making BAD a debilitating condition. The pathophysiology of BAD involves spill-over of bile acids to the colon where bile acids irritate the colonic mucosa and cause osmotic-induced fluid secretion. The aetiology of BAD can be either idiopathic (termed primary BAD or type 2 BAD) or the disease can develop secondary to ileal dysfunction (due to, e.g., intestinal surgery or Chron's disease, termed type 1 BAD) or other conditions interfering with ileal absorption (due to, e.g., cholecystectomy or radiation therapy, termed type 3 BAD).

Irritable bowel syndrome (IBS) with predominant diarrhoea is a common condition in the general population (prevalence of around 4%) and emerging data suggest that around 1/3 suffering from this condition in fact have BAD. Many of these patients remains undiagnosed and thus,inappropriately treated or even untreated. A major reason for this is challenges associated with diagnosing BAD. Several diagnostic modalities have been suggested including 14C-glycocholate breath test, stool test and assessment of 48-hour faecal bile acid output. These tests are cumbersome, time-consuming, and not widely available. The 75selenium homocholic acid taurine (SeHCAT) test is considered the gold standard for the diagnosis of BAD. It measures, via a standard gamma camera, the 7-day retention of a taurine-conjugated bile acid analogue labelled with the gamma-emitter 75selenium. This test provides a quantitative assessment to estimate the severity of BAD, but there is no general agreement regarding its cut-off value and the test is not widely available or even approved for clinical use in many countries outside Europe, including the USA. Furthermore, the SeHCAT test is cumbersome due to its dependence on two visits to the clinic exactly seven days apart, it is expensive, and involves radioactive exposure to the patient. Given the limited availability and the challenges associated with the abovementioned tests, excluding BAD is unfortunately not within current routine investigational algorithms for diarrhoea-predominant IBS, Crohn's disease, or gastrointestinal cancers. In many cases, BAD diagnosis is considered after therapeutic trial using bile acid sequestrants. However, these agents are expensive, often ineffective and/or associated with gastrointestinal side effects in patients with established BAD why their potential as diagnostic tools is limited. Taken together, diagnosing BAD is currently associated with challenges that may preclude relevant treatment of this debilitating condition warranting development of easy and accessible yet safe and effective BAD diagnostics. Recently, the investigators have developed a new BAD diagnostic method based on a single blood sample from the patient. Our approach is based on unbiased, metabolic profiling of serum from BAD patients and carefully matched healthy individuals using comprehensive ultra-high-performance liquid chromatography time-of-flight mass-spectrometry. These comprehensive datasets were subjected to state-of-the-art machine learning and used to build a BAD diagnostic score (BDS) that can distinguish a patient suffering BAD from healthy individuals with high precision (sensitivity of 78% and specificity of 93%). In the present study, the investigators will refine the BDS to distinguish between patients suffering from BAD and patients suffering from other diarrhoeal diseases by using the same methods and data analyses as in the previous project, but in this case applied to serum samples collected from patients referred to diagnostic SeHCAT test, i.e., samples from both test-positive and test-negative patients.

Conditions

Bile Acid Malabsorption; Bile Acid Diarrhea

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

SeHCAT confirmed bile acid diarrhea

Patients referred to a SeHCAT scan due to suspected bile acid diarrhea, who afterwards turned out to be suffering from SeHCAT confirmed bile acid diarrhea

Metabolomics and other blood samples

Intervention Type: DIAGNOSTIC_TEST

Blood samples taken with the objective of identifying a diagnostic test

SeHCAT negative patients

Patients referred to a SeHCAT scan due to suspected bile acid diarrhea, who afterwards turned out to be SeHCAT negative

Metabolomics and other blood samples

Intervention Type: DIAGNOSTIC_TEST

Blood samples taken with the objective of identifying a diagnostic test

Interventions

Metabolomics and other blood samples

Blood samples taken with the objective of identifying a diagnostic test

Intervention Type: DIAGNOSTIC_TEST

Eligibility Criteria

Inclusion Criteria

• SeHCAT referral for suspected bile acid diarrhoea
• Age ≥18 years

Exclusion Criteria

• Diabetes, except type 2 diabetes
• Nephropathy with estimated glomerular filtration rate <30 min/1.73 m2
• Treatment with medicine that cannot be paused for 12 hours
• Hypothyroidism or hyperthyroidism, if not well regulated
• Active or recent (<6 months since last treatment) malignant disease
• Any treatment or condition requiring acute or subacute medical or surgical intervention
• Any condition considered incompatible with trial participation by the investigators

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Gentofte, Copenhagen

OTHER

Sponsor Role: lead

Responsible Party

Asger Lund, MD

MD, PhD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Bispebjerg and Frederiksberg Hospital

Copenhagen, , Denmark

Herlev Gentofte Hospital

Hellerup, , Denmark

Hillerød Hospital

Hillerød, , Denmark

Countries

Denmark

References

Lewinska M, Karhus ML, Ellegaard AG, Romero-Gomez M, Macias RIR, Andersen JB, Knop FK. Serum lipidome unravels a diagnostic potential in bile acid diarrhoea. Gut. 2023 Sep;72(9):1698-1708. doi: 10.1136/gutjnl-2022-329213. Epub 2023 Apr 18.

Reference Type: BACKGROUND

PMID: 37072179 (View on PubMed)

Other Identifiers

BAD-DIVA

Identifier Type: -

Identifier Source: org_study_id