Trial of Ursodeoxycholic Acid (UDCA) for Parkinson's Disease: The "UP" Study

• Status: Completed
• Trial end date: 2021-05-13
• Target enrollment: 0
• Participant gender: All

Summary

The aim of this study is to explore the potential of Ursodeoxycholic acid (UDCA) to slow down the progression of Parkinson's Disease (PD) in a randomised, double-blind, placebo-controlled, "proof of concept" study. The primary objective of the study will be to determine the safety and tolerability of this drug in patients with PD. Participants will be recruited form a cohort of patients who have been diagnosed with PD within the last 3 years and are potentially suitable for this study.

There is strong evidence from previous research and the work carried out by other groups that UDCA rescues the function of the mitochondria (mitochondria are the "powerhouse" of the cell) in PD patient tissue and other models of PD. This suggests that UDCA may slow down the worsening of PD.

UDCA has been in clinical use for the treatment of liver disease (primary biliary cholangitis) for over 30 years. The investigators therefore know that it is safe and well tolerated in patients with liver disease but the investigators don't know yet whether this is also the case in patients with PD. Furthermore, the dose used for patients with liver disease (15 mg/kg) is not high enough for UDCA to get into the brain. The investigators therefore need to double the dose to 30 mg/kg. This higher dose was also safe in clinical trials for liver disease, but is currently not used routinely in clinical practice.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Sheffield Teaching Hospitals NHS Foundation Trust
• Collaborators: Clinical Trials Research Unit, University of Sheffield; J P Moulton Charitable Foundation; JP Moulton Charitable Foundation; PRO.MED.CS Praha a.s.
• Treatments: Ursodeoxycholic Acid

Criteria

Inclusion Criteria:

• Diagnosis of Parkinson's disease: PD is a clinical diagnosis as defined by the Queen Square Brain Bank criteria (bradykinesia defined as slowness of initiation of voluntary movement with progressive reduction in speed and amplitude on repetitive actions and at least one of the following: Rigidity, 4-6 Hz rest tremor). The diagnosis will have been made by the treating clinician and confirmed by the PI on site after review of the clinical history, examination findings and response to PD medication.

The Queen Square brain bank criteria MAY be used to help assist in the diagnosis although this need not be a formal inclusion criteria, and the relevance of a positive family history of PD, or a confirmed genetic basis for an individual's symptoms will be evaluated in the context of other clinical features in determining diagnosis and eligibility.

• Diagnosis of Parkinson's disease ≤ 3 years ago by a clinician with particular expertise in the diagnosis and treatment of movement disorders (typically one of the PIs or their consultant colleagues). The date of diagnosis will be verified by a review of the medical records.

• Subjective improvement of motor impairment on dopaminergic medication, confirmed by PI through personal examination and/or review of medical records

• Hoehn and Yahr stage ≤ 2.5 in the practically defined "ON" medication state. This implies that all patients will be mobile without assistance during their best "ON" medication periods.

• Ability to take study drug

• Ability to communicate in English

• Age 18 - 75 yr of any gender

• Documented informed consent to participate

• Able to comply with study protocol and willing to attend necessary study visits

Exclusion Criteria:

• Diagnosis or suspicion of other cause of parkinsonism such as Multiple system atrophy (MSA) or progressive supranuclear palsy (PSP), drug induced parkinsonism, dystonic tremor or essential tremor will not be recruited.

• Known abnormality on CT or MRI brain imaging considered likely to compromise compliance with trial/protocol/31P-MRS acquisition.

• Known claustrophobia or other reasons why patient could not tolerate or be suitable for 31P-MR Spectroscopy (31P-MRS)

• Current or previous exposure to UDCA

• Current or previous diagnosis of liver disease judged to be significant by the clinical investigator, in particular Primary Biliary Cholangitis (previously referred to as Primary Biliary Cirrhosis, PBC)

• Prior intracerebral surgical intervention for PD (including deep-brain stimulation). Patients who have previously undergone deep brain stimulation, intracerebral administration of growth factors, gene therapies or cell therapies will not be eligible.

• Already actively participating in a trial of a device, drug or surgical treatment for PD

• History of alcoholism

• Women of child - bearing potential (WOCBP)

• Participants who lack the capacity to give informed consent

• Any medical or psychiatric condition which in the investigator's opinion compromises the potential participant's ability to participate

• Concurrent dementia defined by Montreal Cognitive assessment (MoCA) score <25

• Concurrent severe depression defined by a score >16 on the Montgomery- Asberg Depression Rating Scale (MADRS)

• Serum transaminases (such as aspartate transaminase (AST) more than 2 times upper limit of normal.

• Patients on ciclosporin, nitrendipine or dapsone for the treatment of concomitant, general medical conditions.

• Participants with previous or current diagnosis of inflammatory bowel disease (i.e. ulcerative colitis or Crohn's disease)