[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-study-detail:100653380":3},{"organization":4,"outcomesModule":7,"designInfo":73,"detailedDescription":80,"studyPopulation":77,"armGroups":81,"interventions":88,"overallOfficials":93,"centralContacts":101,"locations":108,"responsibleParty":128,"collaborators":131,"id":136,"slug":137,"hasResults":138,"nctId":139,"briefTitle":140,"officialTitle":141,"acronym":142,"eligibilityCriteria":143,"healthyVolunteers":144,"sex":145,"minAge":146,"maxAge":77,"enrollmentInfo":147,"targetDuration":77,"studyType":150,"phases":151,"briefSummary":152,"conditions":153,"keywords":176,"overallStatus":111,"whyStopped":77,"lastUpdateSubmitDate":182,"lastUpdatePostDateStruct":183,"startDateStruct":186,"completionDateStruct":188,"leadSponsor":190,"locationsCount":191},{"fullName":5,"class":6},"University of Cambridge","OTHER",{"primaryOutcomes":8,"secondaryOutcomes":29,"otherOutcomes":39},[9,13,16,19,22,25,27],{"measure":10,"description":11,"timeFrame":12},"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",{"measure":14,"description":15,"timeFrame":12},"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.",{"measure":17,"description":18,"timeFrame":12},"Breath methane levels and faecal archaeal levels","Correlations between breath methane levels (in particles per million) and relative abudance (%) of faecal archaea levels.",{"measure":20,"description":21,"timeFrame":12},"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);",{"measure":23,"description":24,"timeFrame":12},"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.",{"measure":23,"description":26,"timeFrame":12},"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.",{"measure":23,"description":28,"timeFrame":12},"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.",[30,33,36],{"measure":31,"description":32,"timeFrame":12},"Methane breath levels after 18 months of probiotic supplementation","Change in methane breath levels, in particles per million, after 18 months of probiotic supplementation.",{"measure":34,"description":35,"timeFrame":12},"Faecal methanogens after 18 months of probiotic supplementation","Change in percentage of relative abundance of faecal archaea after 18 months of probiotic supplementation.",{"measure":37,"description":38,"timeFrame":12},"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.",[40,43,46,49,51,53,56,58,60,63,66,68,70],{"measure":41,"description":42,"timeFrame":12},"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.",{"measure":44,"description":45,"timeFrame":12},"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.",{"measure":47,"description":48,"timeFrame":12},"Exploratory outcome: change in gut blood markers over 18 months","Change in peripheral Lipopolysaccharide binding protein (LBP), in mg\u002FL, over 18 months in participants with high and low breath methane levels.",{"measure":47,"description":50,"timeFrame":12},"Change in peripheral ghrelin levels, in pg\u002FmL, over 18 months in participants with high and low breath methane levels.",{"measure":47,"description":52,"timeFrame":12},"Change in peripheral Glucagon-like peptide 1(GLP-1), measured in pg\u002FmL, over 18 months in participants with high and low breath methane levels.",{"measure":54,"description":55,"timeFrame":12},"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.",{"measure":54,"description":57,"timeFrame":12},"Change in Addenbrooke's Cognitive Examination III (ACE-III) over 18 months in participants with high and low breath methane levels.",{"measure":54,"description":59,"timeFrame":12},"Change in 90-second semantic fluency over 18 months in participants with high and low breath methane levels.",{"measure":61,"description":62,"timeFrame":12},"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.",{"measure":64,"description":65,"timeFrame":12},"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.",{"measure":64,"description":67,"timeFrame":12},"Change in addenbrooke's cognitive examination-III (ACE-III) over 18 months of probiotic supplementation.",{"measure":64,"description":69,"timeFrame":12},"Change in 90-second semantic fluency scores over 18 months of probiotic supplementation.",{"measure":71,"description":72,"timeFrame":12},"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.",{"allocation":74,"interventionModel":75,"interventionModelDescription":76,"primaryPurpose":6,"observationalModel":77,"timePerspective":77,"maskingInfo":78},"NA","SEQUENTIAL","This study comprises 2 components:\n\nComponent 1 - Observational Study This is a longitudinal observational study.\n\nA total of 200 participants will be enrolled across four cohorts:\n\n1. PwP (n=50),\n2. People at high risk of developing PD (people with REM Sleep behaviour disorders) (n=50),\n3. Other conditions affecting cognition (e.g. dementia, mild cognitive impairment) (n=50),\n4. Healthy controls (n=50).\n\nComponent 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.",null,{"masking":79,"maskingDescription":77,"whoMasked":77},"NONE","Background and Rationale\n\nGut 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.\n\nStudies 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.\n\nThe 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.\n\nBeyond 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.\n\nProbiotics 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.\n\nStudy design:\n\nStudy Description\n\nComponent 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.\n\nComponent 1 of the Met-Pro study is an observational study designed to investigate the role of IMO in PD and related brain disorders.\n\nA total of 200 participants will be enrolled across 4 groups of people:\n\n50 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.\n\nParticipants will be asked to attend 2 visits, 18 months apart, and will undergo:\n\n1. Breath methane testing\n2. Stool analysis to count the abundance of methane-producing archaea\n3. Blood tests to measure markers of the immune system and gut health\n4. Clinical and Cognitive Evaluations using standard neurological and mental function assessments (like the MDS-UPDRS, MoCA, and ACE-III), and questionnaires including: Gastrointestinal Dysfunction Scale for Parkinson's Disease (GIDS-PD), Hospital Anxiety and Depression Scale (HADS), Food Frequency Questionnaire (FFQ), and Short Form Health Survey 36 (SF-36)\n\nFollow-up visits at 18 months will allow assessment of disease progression.\n\nThe 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.\n\nComponent 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.\n\nThis 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.\n\nStudy Objectives\n\nPrimary objectives\n\nTo 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.\n\n1.1. 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.\n\n1.2. Examine the relationship between breath methane concentrations, faecal archaeal populations, and peripheral immune markers.\n\n1.3. Assess links between methane levels, cognitive and motor performance at baseline, and subsequent clinical progression over 18 months.\n\nSecondary objectives\n\n2\\. 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.\n\n3\\. 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.",[82],{"label":83,"type":84,"description":85,"interventionNames":86},"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.",[87],"Other: Probiotic Supplementation with L. reuteri",[89],{"type":6,"name":90,"description":91,"armGroupLabels":92,"otherNames":77},"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.",[83],[94,98],{"name":95,"affiliation":96,"role":97},"Marta Camacho, Dr.","Parkinson's UK Senior Research Fellow John van Geest Centre for Brain Repair, University of Cambridge","PRINCIPAL_INVESTIGATOR",{"name":99,"affiliation":100,"role":97},"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",[102,106],{"name":95,"role":103,"phone":104,"phoneExt":77,"email":105},"CONTACT","+4401223334121","msc72@cam.ac.uk",{"name":99,"role":103,"phone":77,"phoneExt":77,"email":107},"chm27@cam.ac.uk",[109],{"facility":110,"status":111,"city":112,"state":113,"zip":114,"country":115,"countryCode":116,"cosmosGeoPoint":117,"geoPoint":122,"contacts":123},"John Van Geest Centre for Brain Repair - Forvie Site, Robinson Way","RECRUITING","Cambridge","CB2","0PY","United Kingdom","UK",{"type":118,"coordinates":119},"Point",[120,121],0.11667,52.2,{"lat":121,"lon":120},[124],{"name":125,"role":103,"phone":126,"phoneExt":77,"email":127},"Molly O'Reilly","+44 01223 767069","mao36@cam.ac.uk",{"type":97,"investigatorFullName":129,"investigatorTitle":130,"investigatorAffiliation":5,"oldNameTitle":77,"oldOrganization":77},"Marta Camacho","Senior Research Fellow",[132,134],{"name":133,"class":6},"Parkinson's UK",{"name":135,"class":6},"The Functional Gut Clinic","100653380","the-role-of-methanogens-in-the-progression-of-parkinsons-disease-and-related-neurological-conditions-100653380",false,"NCT07786116","The Role of METhanogens in the PROgression Of Parkinson's Disease and Related Neurological Conditions","Met-Pro Study: The Role of METhanogens in the PROgression Of Parkinson's Disease and Related Neurological Conditions","Met-Pro","Inclusion Criteria:\n\nPeople with PD:\n\n* 55 years of age or above;\n* MDS criteria for Idiopathic PD;\n* H\\&Y\\\u003C3.\n\nPeople at high risk of developing PD (people with REM Sleep behaviour disorders):\n\n* 55 years of age or above;\n* RBD diagnosis confirmed by polysomnography.\n\nOther conditions affecting cognition (e.g. dementia, mild cognitive impairment):\n\n* 55 years of age or above;\n* Diagnosis of non-PD dementia or MCI, or, MoCA score ≤25\n\nHealthy Controls:\n\n* 55 years of age or above\n* MoCA total score ≥26.\n\nExclusion Criteria:\n\n* Presence of other neurological disorder, chronic inflammatory\u002Fautoimmune disorder, active cancer, active metabolic disease, diabetes type I and II, and active or latent infection;\n* Use of immunosuppressive drugs within the preceding 12 months;\n* Use of oral\u002Fintravenous steroids within the preceding 3 months;\n* Regular use (more than twice per week) of non-steroidal anti-inflammatory drugs (e.g. ibuprofen, naproxen, diclofenac, meloxicam) or over 75mg aspirin;\n* Participation in other interventional studies, within the preceding 3 months;\n* Consumption of laxatives, stool softeners, stool bulking agents, motility agents, iron supplements and probiotics within the preceding 3 months;\n* Current smoker\n* Inability to understand or speak English fluently.\n\nFor 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).",true,"ALL","55 Years",{"count":148,"type":149},215,"ESTIMATED","INTERVENTIONAL",[74],"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.\n\nRecent 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.\n\nPrevious 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.\n\nMethane 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).\n\nThe 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.\n\nThis study has 2 components:\n\nComponent 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:\n\n50 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.\n\nComponent 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.",[154,155,156,157,158,159,160,161,162,163,164,165,166,167,168,169,170,171,172,173,174,175],"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)",[177,178,179,158,159,180,181],"parkinson","PARKINSON DISEASE","RBD","Ghrelin","intestinal methanogen overgrowth","2026-08-21",{"date":184,"type":185},"2026-08-25","ACTUAL",{"date":187,"type":185},"2025-11-01",{"date":189,"type":149},"2028-03",{"name":5,"class":6},1]