About this trial
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.
Eligibility criteria
This trial accepts healthy volunteersQualifiers
55 years of age or above;
MDS criteria for Idiopathic PD;
H&Y<3.
55 years of age or above;
Disqualifiers
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;
Trial design
Sequential
Treatments tested in this trial
Probiotic Supplementation with L. reuteri
Other intervention15 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.
Treatment groups
Trial outcomes
Primary outcomes
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.
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.
Breath methane levels and faecal archaeal levels
Correlations between breath methane levels (in particles per million) and relative abudance (%) of faecal archaea levels.
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);
Secondary outcomes
Methane breath levels after 18 months of probiotic supplementation
Change in methane breath levels, in particles per million, after 18 months of probiotic supplementation.
Faecal methanogens after 18 months of probiotic supplementation
Change in percentage of relative abundance of faecal archaea after 18 months of probiotic supplementation.
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.
Other outcomes
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.
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.
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.
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.
Sponsors and contacts
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