Trial of Ursodeoxycholic Acid (UDCA) for PD. The 'UP-study'

  • Research type

    Research Study

  • Full title

    A Phase II, Placebo Controlled, Double Blind, Randomised Clinical Trial to assess the safety and tolerability Of 30mg/kg daily Ursodeoxycholic Acid (UDCA) in Patients with Parkinson’s Disease (PD)

  • IRAS ID

    247599

  • Contact name

    Oliver Bandmann

  • Contact email

    o.bandmann@sheffield.ac.uk

  • Sponsor organisation

    Sheffield Teaching Hospitals NHS Foundation Trust

  • Eudract number

    2018-001887-46

  • Clinicaltrials.gov Identifier

    NA, NA

  • Duration of Study in the UK

    1 years, 11 months, 30 days

  • Research summary

    Research Summary
    This proposal addresses the urgent need for disease modifying drugs in Parkinson's disease (PD), the second most common neurodegenerative condition after Alzheimer's disease.

    The aim of this proposal is to explore the potential of UDCA in a randomised, double-blind, placebo-controlled, “proof of concept” study. The primary objective will be to determine its safety and tolerability in PD. We will also use clinical motor rating (MDS-UPDRS/III) as the standard clinical assessment tool to quantify the effect on disease progression.

    We will also explore the effect of UDCA on other clinically relevant parameters such as memory impairment and other non-motor symptoms.

    Participants will be allocated at random to receive either UDCA or placebo 30 mg/kg daily.

    Participants will start by just taking one capsule per day for the first three days. The dose will then be further increased by one capsule every three days until the final dose is reached. This final dose/number of capsules will depend on body weight. Participants will typically reach the final dose within four weeks of the baseline visit and asked to stay on this dose for the subsequent 44 weeks so participants will be taking trial medication for a total of 48 weeks.

    At three study visits (baseline visit/visit 1, visit 5 and visit 6), the key assessments need to be conducted in the absence of regular PD medication. This is so that the assessors are able to get a true picture of the disease without it being masked by the participant's medication.

    Additional procedures for this study include MR spectroscopy; Gait Analysis; provision of a sensor (to gather data on how people walk and move in their natural home environment), blood tests and ECGs.

    Summary of Research
    The UP study has shown that high dose Ursodeoxycholic acid (UDCA, a drug that has been used in liver disease for many years) is safe and tolerable when given to people with Parkinson’s

    Summary of Results
    All side effects observed were in line with what has previously been found with UDCA, most notably diarrhoea and nausea, particularly when first commencing the drug. In all instances these side effects were mild and required no additional treatment.

    Summary of Research
    This was a small study and was primarily designed to show that the drug was safe and tolerable. Our secondary goals were to determine if UDCA may show early promise of slowing down the progression of Parkinson’s over time. This analysis is currently ongoing but currently we think that people with Parkinson’s taking UDCA had less deterioration in their walking when compared to people with Parkinson’s taking the placebo when measured using ‘fitbit’-like digital sensors around their back and legs. Additionally, using specialised MRI scanning techniques to measure the function of mitochondria (the batteries of the brain cells that provide energy for all their functions), we suspect UDCA may be making them work more efficiently.

    Summary of Results
    The next step would be to confirm the possibility that UDCA does slow down the progression of Parkinson’s in a much larger trial that is designed to answer that question more thoroughly and completely, using the new technologies in the trial such as the specialised MRI and the digital sensor to detect changes in Parkinson’s much more sensitively.

  • REC name

    East of England - Cambridgeshire and Hertfordshire Research Ethics Committee

  • REC reference

    18/EE/0280

  • Date of REC Opinion

    8 Nov 2018

  • REC opinion

    Further Information Favourable Opinion