Clinical trial NCT04140760: Probiotic Use in Parkinson's Disease
Official title: Can a 12-week Probiotic Intervention Improve Wellbeing in Parkinson's Disease? A Randomised Double-blind Placebo-controlled Feasibility Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Parkinson Disease
Lead sponsor: Sheffield Hallam University
Sponsor class: OTHER
Collaborators: name: University of Sheffield
name: Sheffield Teaching Hospitals NHS Foundation Trust
First posted: 2019-10-28
Enrollment: 29
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: 1. To evaluate the components and processes needed for a full-scale clinical study: recruitment, randomisation, attrition, probiotic use, stool sample collection, microbiome sequencing and behavioural/cognitive measures and determine the feasibility and patient acceptability of these processes to inform a full-scale study in line with NIHR pilot study guidance.
2. To collect pilot data to determine sample size and power, reliability and sensitivity of selected measures, to maximise the findings and minimise patient burden.

Detailed description: The proposed research is a pilot study with 70 participants, 35 in the probiotic and 35 in the placebo arm of the study. The study will investigate the process of conducting randomised, double-blind, placebo-controlled research about probiotic use in Parkinson's Disease patients. The primary aim of the study is to test elements of the study design for a full-scale clinical study: recruitment, randomisation, probiotic use, stool sample collection and DNA sequencing and behavioural/cognitive measures. The secondary aim is to collect pilot data to determine the sample size, Power and appropriateness of measures needed for a full-scale study that maximises findings and minimises patient burden.

Parkinson's Disease (PD) is a neurodegenerative condition that affects motor functions and a range of non-motor abilities. There is no cure and a definitive cause is not yet known. It has a prevalence of 0.3% in the general population and 1-3% in the population over the age of 65. Globally, it is the second most common neurodegenerative disorder and due to the lack of early diagnosis and effective therapy, represents a large burden for society and healthcare provision. The underlying pathology of PD is associated with accumulation of abnormal clumps of alpha-synuclein protein termed Lewy bodies and Lewy neurites in the central nervous system (CNS) that impede the normal function of brain cells. Evidence from animal studies indicates that the production of alpha-synuclein begins in the gut, and gastro-intestinal problems are a common feature of PD.

The gut contains millions of micro-organisms termed the microbiome. Over the past decade research findings have identified a complex bidirectional interaction between the gastrointestinal (GI) tract and the central nervous system (CNS), the Gut-Brain axis. It is now known that the Gut-Brain axis is adversely affected by PD. Recently, probiotics have been proposed as a potential intervention for systemic and neurological conditions by improving microbiome composition.

Data obtained from this pilot study will be used to identify challenges in conducting research using probiotics in patients with Parkinson's Disease and provide a rationale for conducting a full-scale study including information that may reduce or eliminate problems that limit the successful delivery of a full-scale trial. The investigators will make no claims here about any purported clinical effects of the chosen probiotic.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of idiopathic Parkinson's disease based on UK PD Society Brain Bank criteria.
* Capacity to consent and complete questionnaires.
* Absence of gut/intestinal disorders that would prevent use of a probiotic and/or cause diarrhoea.
* Absence of coincidental neurological condition.
* Using l-dopa plus or minus a dopaminergic agonist.
* Age over 18 and under 80

Exclusion Criteria:

* Unable to consent.
* Use of systemic antibiotics, antifungals, antivirals or antiparasitics (intravenous, intramuscular, or oral).
* Use of commercial probiotics: includes tablets, capsules, lozenges, chewing gum or powders in which probiotic is a primary component. Ordinary dietary components such as fermented beverages/milks, yogurts, foods do not apply.
* Presence of acute viral/bacterial infection disease at the time of sampling (defer sampling until subject recovers). Acute disease is defined as the presence of a moderate or severe illness with or without fever.
* Major surgery of the GI tract, with the exception of cholecystectomy and appendectomy, in the past five years. Any major bowel resection at any time.
* History of active uncontrolled gastrointestinal disorders or diseases including: inflammatory bowel disease (IBD) including ulcerative colitis (mild-moderate-severe), Crohn's disease (mild-moderate-severe), or indeterminate colitis.
* Presence of persistent, infectious gastroenteritis, colitis or gastritis, persistent or chronic diarrhea of unknown etiology, Clostridium difficile infection (recurrent) or Helicobacter pylori infection (untreated).
* Presence of incidental neurological illness.
* Experience of any type of cancer or adenoma less than 5 years previously.
* Age over 80

Primary outcomes:
measure: Patient Adherence to Study questionnaire
timeFrame: Thirteen weeks from study start
measure: Patient Exit Study Scale
timeFrame: 12 and 24 weeks from study start date (only relevant for patients who withdrew).
Secondary outcomes:
measure: Microbiome measurement: 16S rRNA gene sequencing and compositional analysis Microbiome measurement: 16S rRNA gene sequencing and compositional analysis for each patient at pre- and post-intervention
timeFrame: First sample taken at week 1 of entry into study; second sample taken at week 13 after entry to study.
measure: The Unified Parkinson's disease rating scale (UPDRS): Fahn S, Elton R, UPDRS 1987, pp 153-163, 293-304
timeFrame: Measure to be completed at week 1 of entry into study; second evaluation completed at week 13 after entry to study.
measure: The Parkinson's Disease Questionnaire (PDQ-39) Quality of Life Scale
timeFrame: Measure to be completed at week 1 of entry into study; second evaluation completed at week 13 after entry to study.
measure: The Parkinson's Disease Sleep Scale
timeFrame: Measure to be completed at week 1 of entry into study; second evaluation completed at week 13 after entry to study.
measure: Gastrointestinal Symptom Rating Scale (GSRS)
timeFrame: Measure to be completed at week 1 of entry into study; second evaluation completed at week 13 after entry to study.
Other outcomes:
Locations:
city: Sheffield
country: United Kingdom
facility: Sheffield Hallamshire Hospital
state: South Yorkshire
Study officials:
affiliation: Sheffield Hallam University
name: Lynne A Barker, BSc (hons) PhD
role: PRINCIPAL_INVESTIGATOR
References: