Primary biliary cholangitis (PBC) leading to issues with cognitive function around memory and problem-solving. Digestive System Primary biliary cholangitis, primary biliary cirrhosis
Conditions
Interventions
OACS-1 is looking at obeticholic acid (OCA) treatment in patients with stabilised Primary Biliary Cholangitis (PBC) (>2 years since diagnosis) and its effect on cognitive function. Participants will b
Sponsors
Newcastle upon Tyne Hospitals NHS Foundation Trust
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Established diagnosis of PBC based on the presence of =2 of the following key disease characteristics: 1.1. AMA or PBC-specific ANA at a titre of =1/40 1.2. Elevated alkaline phosphatase (above the upper limit of normal for the relevant laboratory) 1.3. Compatible or diagnostic liver biopsy 2. Diagnosed disease duration of =2 years 3. PBC-40 Cognitive Domain score of =12 at screening 4. Stable UDCA dose for 3 months, or not on UDCA if intolerant 5. Willing to complete the study assessment protocols 6. Willing to use highly effective contraception or to practice sexual abstinence to avoid pregnancy for the entire duration of the treatment period 7. Good command of the English language (to ensure that participants are able to comply with cognitive testing) 8. Able to consent, comply with the study protocol, and attend clinic visits 9. Aged between 18 and 75 years (updated 03/05/2023, previously 18 - 65 years)
Exclusion criteria
Exclusion criteria: 1. Clinical suspicion of advanced disease evidenced by a history of =1 of the following: 1.1. Ascites requiring diuretic therapy or percutaneous drainage 1.2. Endoscopically confirmed varices 1.3. Liver biopsy suggesting cirrhosis 1.4. Platelet count 12 cm on ultrasound 1.6. Hepatocellular carcinoma confirmed by biopsy or 2 imaging modalities 1.7. Bilirubin >1.5 x ULN 1.8. Complete biliary obstruction 1.9 Fibroscan >17.6 kPa within the year prior to screening 2. Inter-current disease characterised by cognitive dysfunction (such as dementia or neurodegenerative disease) or clinical suspicion of age-related cognitive decline 3. Inter-current medication characterised by cognitive dysfunction (benzodiazepines, opiates other than codeine phosphate, sleeping pills, regular daily anti-histamine use in the last four weeks, anti-psychotic agents, or recreational drug use) 4. Anticipated change in PBC medication within the duration of the study 5. Contraindications to contrast free MRI assessment (active medical implants, such as cardiac pacemaker and metal implants) 6. Previous exposure to OCA (either in clinical trials or in clinical practice) or fibrate therapy for =3 months and within the last 3 months 7. Regular (more than one week per month) alcohol consumption in excess of recommended safe limits (14 units per week) 8. Active participation in another interventional trial or exposure to another experimental drug within 5 half-lives 9. Pregnancy or planning to get pregnant during the study period 10. Clinical diagnosis of Autoimmune Hepatitis (AIH) 11. Concurrent liver disease of another aetiology 12. Severe pruritus (>11 on PBC-40 pruritus domain) 13. Treating clinician deems the patient is not suitable to participate in the trial based on other criteria apparent during screening or from medical history
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Cognitive function measured using a composite score from the CANTAB cognitive testing platform, derived using individual scores from four core tests: One Touch Stockings of Cambridge (OTS), Paired Associates Learning (PAL), Rapid Visual Information Processing (RVP), and Spatial Working Memory (SWM) at baseline and 26 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Cognitive function measured using the change in score for three additional CANTAB domains: Emotion Recognition Task (ERT), Multitasking Test (MTT), and Reaction Time (RTI) at baseline and 26 weeks 2. Cognitive symptoms measured using the patient-reported PBC-40 Cognitive Domain COGFAIL tool at baseline, 12, and 26 weeks 3. Primary biliary cholangitis (PBC) symptoms measured using the PBC-40 Cognitive Domain, Hospital Anxiety and Depression Scale (HADS), Epworth Sleepiness Scale (ESS), and the Pittsburgh Sleep Quality Index (PSQI) at baseline, 12, and 26 weeks 4. Global quality of life and health utility measured using the EuroQol 5-dimension 5-level quality of life questionnaire (EQ-5D-5L) at baseline, 12, and 26 weeks 5. Impact of Obeticholic Acid treatment on mechanistic brain changes in patients with PBC measured using Diffusion Tensor Imaging (DTI) (change in diffusion fractional anisotropy in the Bilateral Forceps Minor white matter tract) and T1 mapping MRI (change in frontal grey matter T1 relaxation time) at baseline and 26 weeks | — |
Countries
England, United Kingdom
Outcome results
None listed