Parkinson Disease
Conditions
Keywords
probiotic, microbiome
Brief summary
The aim of this study is to evaluate whether the administration of Bacillus Subtilis influences gut and blood biomarkers relevant to the proposed mechanism(s) of action, as well as being acceptable as a regular supplement for people with Parkinson's disease.
Detailed description
Following informed consent, participants will undergo screening. If eligible, they will be invited to attend a baseline visit (week 0) to complete clinical assessments and provide a faecal and blood sample before starting their assigned intervention. Each participant will be randomised 1:1 to visually identical capsules containing either Bacillus Subtilis or placebo to be taken for 24 weeks. Telephone follow-up will be performed at week 8 to ensure compliance and answer any participant questions. Repeat clinical assessments and faecal/blood sample collection will take place at weeks 24 (treatment end date) and 36 (to assess longevity of biomarker changes after the intervention has stopped). Faecal samples will be collected at home within seven days prior to the clinic visits and brought to the appointment. Microbiota composition in faecal samples and blood biomarkers will be analysed in participant samples. Motor and non-motor symptom rating scales will also be administered.
Interventions
DIETARY_SUPPLEMENTBacillus Subtilis
Bacillus Subtilis 1 capsule once daily in the morning (consisting of 10x10\^9 Colony Forming Units)
OTHERPlacebo
1 visually identical placebo capsule once daily in the morning using the same carrier (microcrystalline cellulose) as the active (but not containing Bacillus Subtilis)
Sponsors
University of Edinburgh
Helse Stavanger HF
ADM Protexin
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of Parkinson's disease * Able to provide written informed consent * Over 50 years old * Motor symptom duration over 12 months * Stable dopaminergic medication regime for at least 3 months
Exclusion criteria
* Use of probiotic supplements and probiotic-fortified foods (such as probiotic drinks and yoghurts) within past 3 months * Use of antibiotics within past 3 months * Previous gastrointestinal surgery or chronic organic bowel disorder * History of clinically significant motor fluctuations * History of postural instability or falls * Current smoker * Known or suspected allergy to probiotics * Regular use of antacids, proton pump inhibitors, laxatives or anti-diarrheal drugs * Use of hypoglycaemic or diabetes drugs * Participation in clinical trial of investigational medicinal product within past 3 months * Co-morbidities or other factors that, in the opinion of the investigator, make the patient unlikely to comply with study protocol
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To assess the effect of Bacillus Subtilis on gut microbiome | 24 weeks | Changes in presence and abundance of Bacillus Subtilis and other bacteria in faeces following probiotic administration versus placebo. Non-parametric tests (such as Wilcoxon signed-rank test and permutational multivariate analysis of variance) will be used for alpha and beta diversity analyses, and to identify genera that have significantly changed in abundance. |
| To assess the effects of Bacillus Subtilis on blood biomarkers (sphingolipid profile) | 24 weeks | Changes in sphingolipids following Bacillus Subtilis administration versus placebo measured using liquid chromatography-mass spectrometry |
| To assess the effects of Bacillus Subtilis on blood biomarkers (pro-inflammatory cytokines) | 24 weeks | Changes in pro-inflammatory cytokines following Bacillus Subtilis administration versus placebo measured using V-PLEX Proinflammatory Panel 1 Human Kit |
| To assess the effects of Bacillus Subtilis on blood biomarkers (neurofilament light chain) | 24 weeks | Changes in neurofilament light chain following Bacillus Subtilis administration versus placebo measured using Single Molecule Array assay |
| To assess the effects of Bacillus Subtilis on blood biomarkers (alpha-synuclein species) | 24 weeks | Changes in alpha synuclein species following Bacillus Subtilis administration versus placebo measured using α-syn real-time quaking-induced conversion assays |
| To assess the effects of Bacillus Subtilis on blood biomarkers (lipid profile) | 24 weeks | Changes in cholesterols/triglycerides following Bacillus Subtilis administration versus placebo |
| To assess the effects of Bacillus Subtilis on blood biomarkers (fasting glucose) | 24 weeks | Changes in fasting glucose following Bacillus Subtilis administration versus placebo |
| To assess the effects of Bacillus Subtilis on blood biomarkers (haemoglobin A1C) | 24 weeks | Changes in haemoglobin A1C following Bacillus Subtilis administration versus placebo |
| To evaluate the acceptability of Bacillus Subtilis administration in PD patients | 24 weeks | Descriptive analysis of custom-designed Acceptability Questionnaire which includes four questions on number of missed doses, ease of swallowing, daily dosing schedule, and any other barriers to tablet compliance. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To evaluate the correlation between changes in gut and blood biomarkers following B. subtilis administration and motor/non-motor symptoms | 24 weeks | Correlation between Primary Objectives 1 and 2 and motor/non-motor symptoms: Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Movement Disorder Society Non-Motor Rating Scale (MDS-NMS), Montreal Cognitive Assessment (MoCA) and Parkinson's Disease Questionnaire (PDQ-39) |
Countries
Norway, United Kingdom
Contacts
STUDY_CHAIRDavid P Breen, MBChB
NHS Lothian
Outcome results
None listed