Primary biliary cholangitis (PBC) with cognitive symptoms around memory and problem solving Digestive System Primary biliary cirrhosis
Conditions
Interventions
OACS-2 is a multicentre study that will take place in 4 Specialist PBC centres within an NHS setting across the UK.
OACS-2 is looking at obeticholic acid (brand name OCALIVA) in treating patients wit
Sponsors
Newcastle upon Tyne Hospitals NHS Foundation Trust
Eligibility
Sex/Gender
All
Age
18 Years to 65 Years
Inclusion criteria
Inclusion criteria: 1. Established diagnosis of PBC based on the presence of 2 out of the 3 key disease characteristics: 1.1. AMA or PBC-specific ANA at a titre of 1/40 or greater 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 (either at 13-15 mg/kg) or not on UDCA if intolerant 5. Willing to complete the study assessment protocols 6. For participants of childbearing potential: willing to use highly effective contraception or to practice true 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. Ability to consent, to comply with the study protocol, and to attend clinic visits 9. Aged =18 and =65 years
Exclusion criteria
Exclusion criteria: 1. Clinical suspicion of advanced disease evidenced by a history of one or more 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 conformed by biopsy or 2 imaging modalities 2. Bilirubin >1.5 x upper limit of normal (ULN) 3. Complete biliary obstruction 4. Fibroscan >17.6 kPa within the year prior to or at screening 5. Inter-current disease characterised by cognitive dysfunction (e.g. dementia or neurodegenerative disease) or clinical suspicion of age-related cognitive decline 6. Inter-current medication characterised by cognitive dysfunction (benzodiazepines, opiates other than codeine phosphate, sleeping pills, anti-psychotic agents, regular daily anti-histamine use in the last four weeks, or recreational drug use). 7. Anticipated change in PBC medication within the duration of the study 8. Contraindications to contrast free MRI assessment (active medical implants such as Cardiac pacemaker or metal implants) 9. Previous exposure to OCA (either in clinical trials or in clinical practice) or Fibrate therapy for =3 months and within the last 3 months 10. Regular (more than one week per month) alcohol consumption in excess of recommended safe limits (14 units per week) 11. Active participation in another interventional trial or exposure to another experimental drug within 5 half-lives 12. Pregnancy or planning to get pregnant 13. Clinical diagnosis of AIH overlap 14. Concurrent liver disease of another aetiology 15. Severe pruritus (>11 on PBC-40 pruritus domain) 16. Hypersensitivity to the active substance or to any of the excipients 17. 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 CANTAB score derived from individual scores from four core tests (via the CANTAB cognitive testing platform https://www.cambridgecognition.com/cantab) at baseline and 26 weeks: 1. One Touch Stockings of Cambridge (OTS) 2. Paired Associates Learning (PAL) 3. Rapid Visual Information Processing (RVP) 4. Spatial Working Memory (SWM) | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Cognitive function measured using scores from the following CANTAB domains (via the CANTAB cognitive testing platform https://www.cambridgecognition.com/cantab) at baseline and 26-weeks: 1.1. Emotion Recognition Task (ERT) 1.2. Multitasking Test (MTT) 1.3. Reaction Time (RTI) 2. Patient self-reported cognitive symptom impact measured using the following at baseline, 12, and 26 weeks: 2.1. PBC-40 Cognitive domain 2.2. COGFAIL tool 3. Patient self-reported PBC symptoms measured using the following at baseline, 12, and 26 weeks: 3.1. PBC-40 Cognitive domain 3.2. Hospital Anxiety and Depression Scale (HADS) 3.3. Epworth Sleepiness Scale (ESS) 3.4. Pittsburgh Sleep Quality Index (PSQI) 4. Patient self-reported quality of life measured using the EuroQol 5-dimension 5-level (EQ-5D-5L) questionnaire at baseline, 12, and 26 weeks 5. Mechanistic brain changes measured using MRI at baseline and 26 weeks: 5.1. Change in diffusion fractional anisotropy (FA) in the Bilateral Forceps Minor white matter tract measured using Diffusion Tensor Imaging (DTI) 5.2. Change in frontal grey matter T1 relaxation time measured using T1 mapping | — |
Countries
England, United Kingdom
Contacts
Public ContactAna Alvarez Franco
Outcome results
None listed