The Role of METhanogens in the PROgression Of Parkinson's Disease and Related Neurological Conditions

Summary

Gut problems, such as constipation, can have an important impact on quality of life of people who have them, and have been associated with higher risk of developing neurological diseases such as Parkinson's or Alzheimer's disease.

Recent studies suggest that gut problems may also have implications for the progression of these diseases, as constipation is a risk factor for faster Parkinson's and Alzheimer's progression. However, how constipation and brain diseases are linked is unknown.

Previous research has suggested that gut changes may lead to inflammation, which could play a role in accelerating the progression of both movement and memory problems in Parkinson's and memory and thinking problems in people with cognitive impairment.

Methane is a gas that is naturally produced by microorganisms in the gut. Levels of methane can be measured using a simple breath test. Higher methane levels in the breath are thought to be more common in people with Parkinson's disease (PwP) when compared to people without Parkinson's (healthy controls) and have been associated with gut symptoms, particularly constipation, as well as worse movement problems in PwP, although they are less understood in conditions that affect memory and thinking (like dementia or mild cognitive impairment).

The investigators want to better understand the changes in the gut of PwP and people with cognitive impairment (e.g. mild cognitive impairment or dementia). They will compare breath methane levels in PwP, people with cognitive impairment, people with REM Sleep Behaviour Disorder (a sleep condition linked to a higher risk of developing Parkinson's) and healthy participants. Participants will be followed-up over time to assess how methane levels are linked to changes in the blood and the stools, gut function, and clinical symptoms.

This study has 2 components:

Component 1: observational study, where the study investigators will follow 200 participants over 2 visits, 18 months apart. The study will recruit 4 groups of people:

50 people with Parkinson's disease, 50 people at high risk of developing Parkinson's disease (people with REM Sleep behaviour disorder), 50 people with other conditions affecting cognition (e.g. dementia, mild cognitive impairment), and 50 healthy controls.

Component 2: study with 15 people with Parkinson's, who produce high methane levels, to test whether a probiotic (Lactobacillus reuteri) affects how much methane is produced.

Conditions

• PARKINSON DISEASE (Disorder)
• Parkinson
• Parkinson Disease
• Parkinson s Disease
• REM Behavior Disorder
• REM Sleep Behavior Disorder
• REM Sleep Behavior Disorder (iRBD)
• REM Sleep Behaviour Disorder
• Constipation
• SIBO
• Mild Cognitive Impairment
• Mild Cognitive Impairment (MCI)
• Mild Cognitive Impairment (MCI) Due to Alzheimer's Disease
• Dementia
• Dementia (Diagnosis)
• Dementia Alzheimers
• Dementia MCI (Mild Cognitive Impairment)
• Alzheimer s Disease
• Alzheimer Dementia
• Alzheimer Dementia (AD)
• Alzheimer Disease
• Alzheimer Disease (AD)

Interventions

OTHER

Probiotic Supplementation with L. reuteri

15 PwP with high methane production (≥10ppm on the breath test) identified at the baseline visit in the observational study will be invited to take 1 daily capsule of the probiotic L. reuteri (MSD17938, 1 x 108 CFU) for 18 months.

Sponsors & Collaborators

• Parkinson's UK

  collaborator OTHER

• The Functional Gut Clinic

  collaborator OTHER

• University of Cambridge

  lead OTHER

Principal Investigators

• Marta Camacho, Dr. · Parkinson's UK Senior Research Fellow John van Geest Centre for Brain Repair, University of Cambridge

• Caroline Williams-Gray, Dr. · Dr Caroline Williams-Gray Principal Research Associate, Dept of Clinical Neurosciences, University of Cambridge and Honorary Consultant Neurologist, Cambridge University Hospitals NHS Foundation Trus

Study Design

Allocation

NA

Purpose

OTHER

Masking

NONE

Model

SEQUENTIAL

Eligibility

Min Age

55 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2025-11-01

Primary Completion

2027-06-30

Completion

2028-03-31

Countries

• United Kingdom

Study Locations