Met-Pro Study: The Role of METhanogens in the PROgression Of Parkinson's Disease and Related Neurological Conditions
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 215
- 试验地点
- 1
- 主要终点
- Between-group differences in breath methane levels
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 55 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •People with PD:
- •55 years of age or above;
- •MDS criteria for Idiopathic PD;
- •People at high risk of developing PD (people with REM Sleep behaviour disorders):
- •55 years of age or above;
- •RBD diagnosis confirmed by polysomnography.
- •Other conditions affecting cognition (e.g. dementia, mild cognitive impairment):
- •55 years of age or above;
- •Diagnosis of non-PD dementia or MCI, or, MoCA score ≤25
- •Healthy Controls:
- •55 years of age or above
- •MoCA total score ≥26.
排除标准
- •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.
- •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).
研究组 & 干预措施
People with Parkinson's - High Methane Producers (Probiotic Intervention)
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.
干预措施: Probiotic Supplementation with L. reuteri (Other)
结局指标
主要结局
Between-group differences in breath methane levels
时间窗: Baseline - 18 months
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
时间窗: Baseline - 18 months
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
时间窗: Baseline - 18 months
Correlations between breath methane levels (in particles per million) and relative abudance (%) of faecal archaea levels.
Breath methane levels and blood inflammatory markers
时间窗: Baseline - 18 months
Correlations between breath methane levels (in particles per million) and blood inflammation markers (i.e. Systemic Inflammatory Index and Neutrophil:Lymphocyte ratio);
Breath methane levels and clinical progression
时间窗: Baseline - 18 months
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.
次要结局
- 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)
研究者
Marta Camacho
Senior Research Fellow
University of Cambridge