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

NCT07786116 | Recruiting

• 2 other identifiers: IRAS number: 358942F-2401
• Study Type: interventional
• Target: 215
• Locations: 1 country
• Sites: 1

Brief 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)

Keywords

parkinson; PARKINSON DISEASE; RBD; REM Behavior Disorder; REM Sleep Behavior Disorder; Ghrelin; intestinal methanogen overgrowth

Outcome Measures

Primary Outcomes (7)

• Between-group differences in breath methane levels

  Mean difference in breath methane levels (in particles per million) between the four cohorts (PwP, people at high risk of developing PD, other conditions affecting cognition, healthy controls) at baseline and at 18 months.

  Baseline - 18 months

• Within-group change in breath methane levels

  Mean difference in breath methane levels (in particles per million) within each of the four cohorts (PwP, people at high risk of developing PD, other conditions affecting cognition, healthy controls) at baseline and at 18 months.

  Baseline - 18 months

• Breath methane levels and faecal archaeal levels

  Correlations between breath methane levels (in particles per million) and relative abudance (%) of faecal archaea levels.

  Baseline - 18 months

• Breath methane levels and blood inflammatory markers

  Correlations between breath methane levels (in particles per million) and blood inflammation markers (i.e. Systemic Inflammatory Index and Neutrophil:Lymphocyte ratio);

  Baseline - 18 months

• Breath methane levels and clinical progression

  Correlations between breath methane levels and cognitive function at baseline, at follow-up and rate of change (difference between scores in the Montreal Cognitive Assessment at follow-up and baseline) over 18-month follow-up.

  Baseline - 18 months

• Breath methane levels and clinical progression

  Correlations between breath methane levels and cognitive function at baseline, at follow-up and rate of change (difference between scores Addenbrooke's Cognitive Examination III at follow-up and baseline) over 18-month follow-up.

  Baseline - 18 months

• Breath methane levels and clinical progression

  Correlations between breath methane levels and motor function at baseline, at follow-up and rate of change (difference between scores in Movement Disorder Society-Unified Parkinson's Disease Rating Scale Part III at follow-up and baseline) over 18-month follow-up in the PD and RBD cohort.

  Baseline - 18 months

Secondary Outcomes (3)

• Methane breath levels after 18 months of probiotic supplementation

  Baseline - 18 months

• Faecal methanogens after 18 months of probiotic supplementation

  Baseline - 18 months

• Change in systemic blood inflammation markers after 18 months of probiotic supplementation

  Baseline - 18 months

Other Outcomes (13)

• Exploratory outcome: change in gut symptoms over 18 months

  Baseline - 18 months

• Exploratory outcome: change in gut markers after 18 month of probiotic supplementation

  Baseline - 18 months

• Exploratory outcome: change in gut blood markers over 18 months

  Baseline - 18 months

Study Arms (1)

People with Parkinson's - High Methane Producers (Probiotic Intervention)

EXPERIMENTAL

15 with high methane production identified at the baseline visit in the observational study will be invited to take 1 daily capsule of the probiotic for 18 months.

Other: Probiotic Supplementation with L. reuteri

Interventions

Probiotic Supplementation with L. reuteri OTHER

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.

People with Parkinson's - High Methane Producers (Probiotic Intervention)

Eligibility Criteria

• Age: 55 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• People with PD:
• years of age or above;
• MDS criteria for Idiopathic PD;
• H\&Y\<3.
• People at high risk of developing PD (people with REM Sleep behaviour disorders):
• years of age or above;
• RBD diagnosis confirmed by polysomnography.
• Other conditions affecting cognition (e.g. dementia, mild cognitive impairment):
• years of age or above;
• Diagnosis of non-PD dementia or MCI, or, MoCA score ≤25
• Healthy Controls:
• years of age or above
• MoCA total score ≥26.

You may not qualify if:

• Presence of other neurological disorder, chronic inflammatory/autoimmune disorder, active cancer, active metabolic disease, diabetes type I and II, and active or latent infection;
• Use of immunosuppressive drugs within the preceding 12 months;
• Use of oral/intravenous steroids within the preceding 3 months;
• Regular use (more than twice per week) of non-steroidal anti-inflammatory drugs (e.g. ibuprofen, naproxen, diclofenac, meloxicam) or over 75mg aspirin;
• Participation in other interventional studies, within the preceding 3 months;
• Consumption of laxatives, stool softeners, stool bulking agents, motility agents, iron supplements and probiotics within the preceding 3 months;
• Current smoker
• Inability to understand or speak English fluently.

Sponsors & Collaborators

• University of Cambridge: lead
• Parkinson's UK: collaborator
• The Functional Gut Clinic: collaborator

Study Sites (1)

John Van Geest Centre for Brain Repair - Forvie Site, Robinson Way

Cambridge, CB2, 0PY, United Kingdom

RECRUITING

Related Publications (3)

• Camacho M, Greenland JC, Williams-Gray CH. The Gastrointestinal Dysfunction Scale for Parkinson's Disease. Mov Disord. 2021 Oct;36(10):2358-2366. doi: 10.1002/mds.28675. Epub 2021 Jun 16.

  PMID: 34133059 BACKGROUND

• Ojetti V, Petruzziello C, Migneco A, Gnarra M, Gasbarrini A, Franceschi F. Effect of Lactobacillus reuteri (DSM 17938) on methane production in patients affected by functional constipation: a retrospective study. Eur Rev Med Pharmacol Sci. 2017 Apr;21(7):1702-1708.

  PMID: 28429333 BACKGROUND

• Camacho M, Macleod AD, Maple-Grodem J, Evans JR, Breen DP, Cummins G, Wijeyekoon RS, Greenland JC, Alves G, Tysnes OB, Lawson RA, Barker RA, Williams-Gray CH. Early constipation predicts faster dementia onset in Parkinson's disease. NPJ Parkinsons Dis. 2021 May 26;7(1):45. doi: 10.1038/s41531-021-00191-w.

  PMID: 34039994 BACKGROUND

MeSH Terms

Conditions

Parkinson Disease; REM Sleep Behavior Disorder; Constipation; Cognitive Dysfunction; Dementia; Disease; Alzheimer Disease

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; REM Sleep Parasomnias; Parasomnias; Sleep Wake Disorders; Mental Disorders; Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Cognition Disorders; Neurocognitive Disorders; Pathologic Processes; Tauopathies

Study Officials

• Marta Camacho, Dr.

  Parkinson's UK Senior Research Fellow John van Geest Centre for Brain Repair, University of Cambridge

  PRINCIPAL INVESTIGATOR

• 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

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Marta Camacho, Dr.

CONTACT

+4401223334121; msc72@cam.ac.uk

Caroline Williams-Gray, Dr.

CONTACT

chm27@cam.ac.uk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior Research Fellow

Model Details: This study comprises 2 components: Component 1 - Observational Study This is a longitudinal observational study. A total of 200 participants will be enrolled across four cohorts: 1. PwP (n=50), 2. People at high risk of developing PD (people with REM Sleep behaviour disorders) (n=50), 3. Other conditions affecting cognition (e.g. dementia, mild cognitive impairment) (n=50), 4. Healthy controls (n=50). Component 2: experimental medicine study in which 15 participants with PD and high methane levels will receive the probiotic Lactobacillus reuteri and investigate whether its consumption affects methane production.

Study Record Dates

• First Submitted: July 8, 2026
• First Posted: August 25, 2026
• Study Start: November 1, 2025
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): March 1, 2028
• Last Updated: August 25, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will share
• Time Frame: Anonymised study data will be made available following study completion and the publication of the main results.
• Access Criteria: Anonymised study data will be made available upon reasonable request.

Locations

GB (1)