Role of the Gut-microbiota on Ageing and Neurodegeneration: a Clinical and Brain Imaging Study
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 200
- 试验地点
- 3
- 主要终点
- Brain structural and functional properties
研究概览
简要总结
Neurodegenerative diseases are a major health concern due to their growing societal implications and economic costs. The identification of early markers of pathogenic mechanisms is one of the current main challenges. The gut-brain axis has become a primary target because of its transversal role across the neurodegenerative spectrum and its effect on cognition. However, despite recent progress, how changes in the gut-microbiota composition can affect the human brain is still unclear.
The goal of this observational study is to characterise the gut-microbiota composition associated with alterations in brain structure and function during the ageing process and across neurodegenerative disorders. This is based on recent studies showing that changes in the human brain and in the microbiota composition, can indicate very sensitively and in a predictive way pathological development and, consequently, be used as markers of neurodegenerative diseases.
The main questions it aims to answer are:
- How variation in the gut-microbiota composition correlates with the normal brain ageing trajectory?
- How dysregulation in the gut-microbiota correlates with pathological changes in brain regions in specific neurodegenerative disorders?
- Can the impact of the gut-microbiota on the brain be modulated by blood biomarkers?
The investigators will recruit 40 young healthy participants, 40 old healthy participants, 40 participants with prodromal Alzheimer's Disease, 40 participants with Parkinson's Disease and 40 participants with Multiple Sclerosis.
Participants will undergo the following examinations:
- Magnetic Resonance Imaging
- Analysis of a stool sample
- Analysis of a blood sample
- Neuropsychological assessment
- Questionnaires on eating habits
详细描述
Recent studies show that alterations in the microbiota profile has been observed in the ageing process and across neurodegenerative disorders and it has been associated with cognitive decline and disease-specific clinical symptoms.
The objective of this multicenter observational cross-sectional cohort study is to characterise how changes in the gut-microbiota profile may affect brain changes during the physiological ageing processes and across neurodegenerative disorders with different etiopathogenesis.
The investigators will combine novel magnetic resonance imaging and biological techniques to test these hypotheses:
- Specific functional and structural changes, which reflect unsuccessful compensatory mechanisms to counteract ageing, are associated with changes in the gut-microbiota composition.
- Neurodegenerative disorders (prodromal Alzheimer's Disease, Parkinson's Disease, Multiple Sclerosis) show unique changes in the gut-microbiome profile, associated with specific structural and functional brain changes.
- The microbiota profile characterizing the unsuccessful ageing and different neurodegenerative diseases is associated with alterations in blood biomarkers.
For this study the investigators plan to recruit 80 healthy subjects divided into two groups (40 subjects aged 20-50 years and 40 subjects aged 60-90 years) and 120 patients divided into three groups (40 patients with prodromal Alzheimer's Disease, 40 patients with Parkinson's Disease and 40 patients with Multiple Sclerosis).
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Cross Sectional
入排标准
- 年龄范围
- 20 Years 至 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy Young and Old Subjects:
- •20-50 or 60-90 years old
- •Cognitively healthy (Mini-Mental State examination ≥ 26)
- •Absence of significant neurological disorders
- •Patients with prodromal Alzheimer's Disease:
- •Subjective cognitive complaint (corroborated by the informant)
- •Episodic memory deficit on neuropsychological testing
- •Clinical Dementia Rating = 0.5
- •Mini-Mental State Examination (MMSE) > 23
- •Independently functioning in activities of daily living
- •Patients with Parkinson's Disease:
- •Recent diagnosis of Parkinson's Disease
- •Mild-moderate score at the Unified Parkinson's Disease Rating Scale (UPDRS)
- •Cognitively healthy (Mini-Mental State examination ≥ 26)
- •In case of taking medications for Parkinson's Disease: stable dosage for at least 6 months
- •Patients with Multiple Sclerosis:
- •Recent diagnosis of relapsing-remitting Multiple Sclerosis
- •Expanded Disability Status Scale score ≤ 4.0
- •Cognitively healthy (Mini-Mental State examination ≥ 26)
- •In case of taking medications for Multiple Sclerosis: stable dosage for at least 6 months.
排除标准
- •For both healthy participants and patients:
- •Contraindications to magnetic resonance imaging (metal implant in body, known claustrophobia, pacemakers)
- •Severe comorbidities
- •Antibiotics treatments over the last 3 months
研究组 & 干预措施
Young Healthy Subjects (N = 40)
- 20-50 years old
- Cognitively healthy (Mini-Mental State examination ≥ 26)
- Absence of significant neurological disorders
干预措施: Magnetic Resonance Imaging (Diagnostic Test)
Young Healthy Subjects (N = 40)
- 20-50 years old
- Cognitively healthy (Mini-Mental State examination ≥ 26)
- Absence of significant neurological disorders
干预措施: Neuropsychological protocol (Behavioral)
Young Healthy Subjects (N = 40)
- 20-50 years old
- Cognitively healthy (Mini-Mental State examination ≥ 26)
- Absence of significant neurological disorders
干预措施: Eating habits (Behavioral)
Young Healthy Subjects (N = 40)
- 20-50 years old
- Cognitively healthy (Mini-Mental State examination ≥ 26)
- Absence of significant neurological disorders
干预措施: Microbiome analyses (Diagnostic Test)
Young Healthy Subjects (N = 40)
- 20-50 years old
- Cognitively healthy (Mini-Mental State examination ≥ 26)
- Absence of significant neurological disorders
干预措施: Inflammatory markers (Diagnostic Test)
Old Healthy Subjects (N = 40)
- 60-90 years old
- Cognitively healthy (Mini-Mental State examination ≥ 26)
- Absence of significant neurological disorders
干预措施: Magnetic Resonance Imaging (Diagnostic Test)
Old Healthy Subjects (N = 40)
- 60-90 years old
- Cognitively healthy (Mini-Mental State examination ≥ 26)
- Absence of significant neurological disorders
干预措施: Neuropsychological protocol (Behavioral)
Old Healthy Subjects (N = 40)
- 60-90 years old
- Cognitively healthy (Mini-Mental State examination ≥ 26)
- Absence of significant neurological disorders
干预措施: Eating habits (Behavioral)
Old Healthy Subjects (N = 40)
- 60-90 years old
- Cognitively healthy (Mini-Mental State examination ≥ 26)
- Absence of significant neurological disorders
干预措施: Microbiome analyses (Diagnostic Test)
Old Healthy Subjects (N = 40)
- 60-90 years old
- Cognitively healthy (Mini-Mental State examination ≥ 26)
- Absence of significant neurological disorders
干预措施: Inflammatory markers (Diagnostic Test)
Patients with prodromal Alzheimer's Disease (N = 40)
- Subjective cognitive complaint (corroborated by the informant)
- Episodic memory deficit on neuropsychological testing
- Clinical Dementia Rating = 0.5
- Mini-Mental State Examination (MMSE) > 23
- Independently functioning in activities of daily living
干预措施: Magnetic Resonance Imaging (Diagnostic Test)
Patients with prodromal Alzheimer's Disease (N = 40)
- Subjective cognitive complaint (corroborated by the informant)
- Episodic memory deficit on neuropsychological testing
- Clinical Dementia Rating = 0.5
- Mini-Mental State Examination (MMSE) > 23
- Independently functioning in activities of daily living
干预措施: Neuropsychological protocol (Behavioral)
Patients with prodromal Alzheimer's Disease (N = 40)
- Subjective cognitive complaint (corroborated by the informant)
- Episodic memory deficit on neuropsychological testing
- Clinical Dementia Rating = 0.5
- Mini-Mental State Examination (MMSE) > 23
- Independently functioning in activities of daily living
干预措施: Eating habits (Behavioral)
Patients with prodromal Alzheimer's Disease (N = 40)
- Subjective cognitive complaint (corroborated by the informant)
- Episodic memory deficit on neuropsychological testing
- Clinical Dementia Rating = 0.5
- Mini-Mental State Examination (MMSE) > 23
- Independently functioning in activities of daily living
干预措施: Microbiome analyses (Diagnostic Test)
Patients with prodromal Alzheimer's Disease (N = 40)
- Subjective cognitive complaint (corroborated by the informant)
- Episodic memory deficit on neuropsychological testing
- Clinical Dementia Rating = 0.5
- Mini-Mental State Examination (MMSE) > 23
- Independently functioning in activities of daily living
干预措施: Inflammatory markers (Diagnostic Test)
Patients with prodromal Alzheimer's Disease (N = 40)
- Subjective cognitive complaint (corroborated by the informant)
- Episodic memory deficit on neuropsychological testing
- Clinical Dementia Rating = 0.5
- Mini-Mental State Examination (MMSE) > 23
- Independently functioning in activities of daily living
干预措施: Alzheimer's Disease biomarkers (Diagnostic Test)
Patients with Parkinson's Disease (N = 40)
- Recent diagnosis of Parkinson's Disease
- Mild-moderate score at the Unified Parkinson's Disease Rating Scale (UPDRS)
- Cognitively healthy (Mini-Mental State examination ≥ 26)
- In case of taking medications for Parkinson's Disease: stable dosage for at least 6 months
干预措施: Magnetic Resonance Imaging (Diagnostic Test)
Patients with Parkinson's Disease (N = 40)
- Recent diagnosis of Parkinson's Disease
- Mild-moderate score at the Unified Parkinson's Disease Rating Scale (UPDRS)
- Cognitively healthy (Mini-Mental State examination ≥ 26)
- In case of taking medications for Parkinson's Disease: stable dosage for at least 6 months
干预措施: Neuropsychological protocol (Behavioral)
Patients with Parkinson's Disease (N = 40)
- Recent diagnosis of Parkinson's Disease
- Mild-moderate score at the Unified Parkinson's Disease Rating Scale (UPDRS)
- Cognitively healthy (Mini-Mental State examination ≥ 26)
- In case of taking medications for Parkinson's Disease: stable dosage for at least 6 months
干预措施: Eating habits (Behavioral)
Patients with Parkinson's Disease (N = 40)
- Recent diagnosis of Parkinson's Disease
- Mild-moderate score at the Unified Parkinson's Disease Rating Scale (UPDRS)
- Cognitively healthy (Mini-Mental State examination ≥ 26)
- In case of taking medications for Parkinson's Disease: stable dosage for at least 6 months
干预措施: Microbiome analyses (Diagnostic Test)
Patients with Parkinson's Disease (N = 40)
- Recent diagnosis of Parkinson's Disease
- Mild-moderate score at the Unified Parkinson's Disease Rating Scale (UPDRS)
- Cognitively healthy (Mini-Mental State examination ≥ 26)
- In case of taking medications for Parkinson's Disease: stable dosage for at least 6 months
干预措施: Inflammatory markers (Diagnostic Test)
Patients with Multiple Sclerosis (N = 40)
- Recent diagnosis of relapsing-remitting Multiple Sclerosis
- Expanded Disability Status Scale score ≤ 4.0
- Cognitively healthy (Mini-Mental State examination ≥ 26)
- In case of taking medications for Multiple Sclerosis: stable dosage for at least 6 months
干预措施: Magnetic Resonance Imaging (Diagnostic Test)
Patients with Multiple Sclerosis (N = 40)
- Recent diagnosis of relapsing-remitting Multiple Sclerosis
- Expanded Disability Status Scale score ≤ 4.0
- Cognitively healthy (Mini-Mental State examination ≥ 26)
- In case of taking medications for Multiple Sclerosis: stable dosage for at least 6 months
干预措施: Neuropsychological protocol (Behavioral)
Patients with Multiple Sclerosis (N = 40)
- Recent diagnosis of relapsing-remitting Multiple Sclerosis
- Expanded Disability Status Scale score ≤ 4.0
- Cognitively healthy (Mini-Mental State examination ≥ 26)
- In case of taking medications for Multiple Sclerosis: stable dosage for at least 6 months
干预措施: Eating habits (Behavioral)
Patients with Multiple Sclerosis (N = 40)
- Recent diagnosis of relapsing-remitting Multiple Sclerosis
- Expanded Disability Status Scale score ≤ 4.0
- Cognitively healthy (Mini-Mental State examination ≥ 26)
- In case of taking medications for Multiple Sclerosis: stable dosage for at least 6 months
干预措施: Microbiome analyses (Diagnostic Test)
Patients with Multiple Sclerosis (N = 40)
- Recent diagnosis of relapsing-remitting Multiple Sclerosis
- Expanded Disability Status Scale score ≤ 4.0
- Cognitively healthy (Mini-Mental State examination ≥ 26)
- In case of taking medications for Multiple Sclerosis: stable dosage for at least 6 months
干预措施: Inflammatory markers (Diagnostic Test)
结局指标
主要结局
Brain structural and functional properties
时间窗: Day 1
Brain structural and functional properties will be derived from a multi-modal Magnetic Resonance Imaging protocol.
Microbiome profile
时间窗: Day 1
Microbiome profile will be derived from a stool sample obtained from participants.
次要结局
- Cognitive functioning(Day 1)
- Concentration of blood inflammatory markers(Day 1)
- Eating habits(Day 1)
研究者
Nicola Filippini
Principal Investigator
IRCCS San Camillo, Venezia, Italy