An interventional study of Probiotic Supplementation with L. reuteri in PARKINSON DISEASE (Disorder), Parkinson and Parkinson Disease, sponsored by University of Cambridge. Recruiting at 1 site in United Kingdom. Open to participants aged 55 Years and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-08-25.
Sponsored by University of Cambridge · Not applicable, Interventional, and Other
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.
Background and Rationale
Gut microbes are crucial for health. They produce important substances like vitamines, metabolites, and gases, such as hydrogen and methane. Intestinal Methanogen Overgrowth (IMO) occurs when there is an overgrowth of methane-producing organisms called archaea. IMO can be measured with a non-invasive breath test is strongly associated with whole gut transit time and constipation.
Studies suggest that approximately half of people with Parkinson's disease (PD) test positive for IMO, and a positive test has been linked to worse movement control (motor performance) and motor fluctuations.
The presence of high methane levels is known to slow gut transit, cause constipation, and can hinder the absorption of levodopa, the main drug for PD symptom relief. This, in turn, may worsen inflammation and affect the gut lining. Crucially, constipation and body-wide inflammation are predictors of cognitive decline in PD, however, no study has yet examined the link between IMO and cognition.
Beyond their role in the gut, these methane-producing microbes might directly impact the body and the brain. They can produce their own signaling molecules, like neurotransmitters and metabolites, and may even trigger inflammatory pathways. While some research suggests methane may have neuroprotective effects in animals, other studies link high methane levels to metabolic issues in humans, highlighting the urgent need for human-focused investigation.
Probiotics such as Limosilactobacillus reuteri, also known as *L. reuteri* has long been used as a food supplement, with anti-inflammatory and gut-barrier-supporting effects. One study has previously reported that supplementation with the strain L. reuteri DSM17938 reduced methane production in constipated individuals. The strain L. reuteri DSM17938 is safe, colonises the gut, is available in chewable form, and has been associated with reduced inflammation and methane production. However, further studies are needed to investigate whether this strain reduces methane production and what impact it may have in people with PD.
Study design:
Study Description
Component 1 - Observational Study Despite the relationship between high methane breath levels and worse motor function in Parkinson's disease, the relationship between methane, cognition, and disease progression has not been investigated.
Component 1 of the Met-Pro study is an observational study designed to investigate the role of IMO in PD and related brain disorders.
A total of 200 participants will be enrolled across 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.
Participants will be asked to attend 2 visits, 18 months apart, and will undergo:
Follow-up visits at 18 months will allow assessment of disease progression.
The primary aim is to assess whether breath methane can serve as a non-invasive biomarker of cognition, motor function, and progression in PD and related conditions, and to explore links between methane, archaeal abundance, systemic inflammation, and gut-brain interactions.
Component 2 - Experimental medicine substudy A small group of 15 participants with PD, who test positive for intestinal methanogen overgrowth (≥10 ppm of methane in the breath), will take the probiotic Limosilactobacillus reuteri as a daily chewable supplement for 18 months. The primary purpose is to see if taking the probiotic reduces breath methane levels and the number of archaea in the stool. Exploratory analyses will assess potential effects on cognition, motor symptoms, and gut function.
This part of the study will provide essential first evidence on whether targeting methane-producing microbes is a viable therapeutic strategy for PD and will inform the design of larger, more definitive clinical trials in the future.
Study Objectives
Primary objectives
To determine how intestinal methanogen overgrowth relates to inflammation and disease course, and whether breath methane testing could serve as a longitudinal and predictive biomarker in PD and other neurodegenerative disorders.
1.1. Measure and compare methane levels in exhaled breath among individuals with PD, prodromal PD, other conditions that affect cognition (e.g. AD, mild cognitive impairment), and healthy controls, and assess changes over an 18-month period.
1.2. Examine the relationship between breath methane concentrations, faecal archaeal populations, and peripheral immune markers.
1.3. Assess links between methane levels, cognitive and motor performance at baseline, and subsequent clinical progression over 18 months.
Secondary objectives
2. To construct a prognostic model that incorporates breath methane levels and other gut-related biomarkers to predict neurodegenerative disease progression or the onset of disease in at-risk groups.
3. To test whether probiotic supplementation with Lactobacillus reuteri lowers methane exhalation and faecal archaeal abundance, and to evaluate its impact on systemic inflammatory indices and gut function measures in PD.
4,573 studies on the registry are indexed under Parkinson Disease; 1,086 are open to participants now.
This study's planned enrollment of 215 is above the median of 40 across 3,353 interventional studies indexed under Parkinson Disease.
Browse Parkinson Disease studies →University of Cambridge is the lead sponsor of 116 studies on the registry; 23 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
People with PD:
People at high risk of developing PD (people with REM Sleep behaviour disorders):
Other conditions affecting cognition (e.g. dementia, mild cognitive impairment):
Healthy Controls:
Exclusion Criteria:
For participants in Component 2 of the study (Experimental Medicine Study), additional exclusion criteria will be in place, namely, known allergy to any of the probiotic's ingredients: Bulking agent (isomalt), sweetener (xylitol), L. reuteri DSM 17938, strawberry flavouring and flavour enhancer (citric acid).
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Short tests of memory and thinking, each scored out of 30. Lower scores suggest more difficulty; criteria give a range, either to include people with memory problems or to leave them out.
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
MMSE and MoCA
Short tests of memory and thinking, each scored out of 30. Lower scores suggest more difficulty; criteria give a range, either to include people with memory problems or to leave them out.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Autoimmune disease
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Immunosuppression
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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
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.
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.
Time frame: 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.
Time frame: 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.
Time frame: 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);
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Baseline - 18 months
Methane breath levels after 18 months of probiotic supplementation
Change in methane breath levels, in particles per million, after 18 months of probiotic supplementation.
Time frame: Baseline - 18 months
Faecal methanogens after 18 months of probiotic supplementation
Change in percentage of relative abundance of faecal archaea after 18 months of probiotic supplementation.
Time frame: Baseline - 18 months
Change in systemic blood inflammation markers after 18 months of probiotic supplementation
Change in systemic blood inflammation markers (Systemic Inflammatory Index, Neutrophil:Lymphocyte ratio) after 18 months of probiotic supplementation.
Time frame: Baseline - 18 months
Exploratory outcome: change in gut symptoms over 18 months
Change in gut symptoms as self-reported via the Gastrointestinal Dysfunction Scale for Parkinson's Disease (GIDS-PD) over 18 months in participants with high and low breath methane levels.
Time frame: Baseline - 18 months
Exploratory outcome: change in gut markers after 18 month of probiotic supplementation
Change in Whole Transit Time, measured in hours, after 18 months of probiotic supplementation.
Time frame: Baseline - 18 months
Exploratory outcome: change in gut blood markers over 18 months
Change in peripheral Lipopolysaccharide binding protein (LBP), in mg/L, over 18 months in participants with high and low breath methane levels.
Time frame: Baseline - 18 months
Exploratory outcome: change in gut blood markers over 18 months
Change in peripheral ghrelin levels, in pg/mL, over 18 months in participants with high and low breath methane levels.
Time frame: Baseline - 18 months
Exploratory outcome: change in gut blood markers over 18 months
Change in peripheral Glucagon-like peptide 1(GLP-1), measured in pg/mL, over 18 months in participants with high and low breath methane levels.
Time frame: Baseline - 18 months
Exploratory outcome: change in cognitive function over 18 months
Change in Montreal Cognitive Assessment (MoCA) scores over 18 months in participants with high and low breath methane levels.
Time frame: Baseline - 18 months
Exploratory outcome: change in cognitive function over 18 months
Change in Addenbrooke's Cognitive Examination III (ACE-III) over 18 months in participants with high and low breath methane levels.
Time frame: Baseline - 18 months
Exploratory outcome: change in cognitive function over 18 months
Change in 90-second semantic fluency over 18 months in participants with high and low breath methane levels.
Time frame: Baseline - 18 months
Exploratory outcome: change in motor function over 18 months
Change in motor function Movement Disorder Society-Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS III) over 18 months in PD participants with high and low breath methane levels.
Time frame: Baseline - 18 months
Exploratory outcome: change in cognitive function after 18 month of probiotic supplementation
Change in montreal cognitive assessment (MoCA) scores over 18 months of probiotic supplementation.
Time frame: Baseline - 18 months
Exploratory outcome: change in cognitive function after 18 month of probiotic supplementation
Change in addenbrooke's cognitive examination-III (ACE-III) over 18 months of probiotic supplementation.
Time frame: Baseline - 18 months
Exploratory outcome: change in cognitive function after 18 month of probiotic supplementation
Change in 90-second semantic fluency scores over 18 months of probiotic supplementation.
Time frame: Baseline - 18 months
Exploratory outcome: change in motor function after 18 months of probiotic supplementation
Change in motor function Movement Disorder Society-Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS III) over 18 months of probiotic supplementation.
Time frame: Baseline - 18 months
Plan to share: Yes — Study data will be made available for sharing after completion of quality control procedures. Data will be stored in standard formats to facilitate sharing and released in accordance with Sponsor policies and relevant national and international data transparency frameworks. No personally identifiable information will be disclosed.
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.
Started Nov 2025 (actual). Primary completion is estimated for Jun 2027, 19 months after the start.
Of 1,291 non-industry interventional studies with no phase under Parkinson Disease, half reached primary completion within 24 months of starting (the median), counting those still running; a quarter within 11 and three quarters within 44. This study's planned 19 months is below that.
Counting every sponsor, half of 1,367 studies reached it within 25 months; a quarter within 11 and three quarters within 44.
How these figures are worked out, and which studies are left out of them.
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