Mediterranean Diet Effects on Parkinson's Disease (MED-PARK): a Randomized Controlled Trial
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 44
- 试验地点
- 2
- 主要终点
- Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) I+II
研究概览
简要总结
Currently, there are no disease-modifying treatments for Parkinson's disease (PD), the second most common neurodegenerative disorder worldwide, making it crucial to find interventions that can change the disease's trajectory. Epidemiological studies suggest that the Mediterranean diet (MD) is linked to improved motor and non-motor symptoms, slower disease progression, and lower mortality in PD patients. However, few interventional studies have explored this connection. This study assesses whether an MD can improve motor and non-motor symptoms in PD patients. Additionally, the study will examine the effects of the diet on a patient's quality of life, gastrointestinal symptomatology, adaptive immune system, fecal and nasal microbiome, and fecal and urinary metabolomics.
This is a randomized, controlled, non-pharmacological, single-center, masked trial with two parallel groups. It will evaluate the safety and efficacy of the MD on motor and non-motor symptoms reported by PD patients. Forty-four participants, aged 40-85, meeting the inclusion criteria will be enrolled and block-randomized into two groups: one maintaining their usual diet (control) and the other following a MD for six months (intervention).
The primary outcome is patient-reported symptoms, measured using the MDS-UPDRS I+II score.
Secondary outcomes include the analysis of adaptive immune system cells, nasal and fecal microbiome composition, and inflammatory and metabolic markers. Additional assessments include disease severity (MDS-UPDRS), non-motor symptoms (Non-Motor Symptoms Scale), participant well-being (36-Item Short Form Health Survey), gastrointestinal symptoms (Gastrointestinal Symptom Rating Scale and Patient Assessment of Constipation Quality of Life), and the intensity of dopaminergic therapy (levodopa equivalents). Evaluations will be performed at baseline and after six months.
详细描述
PD is a progressive neurodegenerative disorder marked by both motor and non-motor symptoms, leading to reduced quality of life and increased economic burden for patients and caregivers. Prior to diagnosis, patients often experience a prodromal phase characterized by symptoms such as anosmia, constipation, and sleep disturbances. PD is the second most common neurodegenerative disease globally and the fastest-growing, with an increasing prevalence since 1990.
The disease is linked to the buildup of α-synuclein in Lewy bodies within the brain and neuroinflammation caused by microglial activation. This process results in the degeneration of dopaminergic neurons in the substantia nigra, which is central to PD pathology. Recent research has highlighted the role of immune dysfunction in PD, with alterations observed in adaptive and innate immune responses. A reduction in specific T cells (e.g., CD4+ T cells, Th2, Th17, and T regulatory cells) and a shift towards a pro-inflammatory Th1 response have been associated with neuronal damage in PD. Moreover, aberrant α-synuclein may trigger an adaptive immune response, highlighting the relevance of the immune system as a potential therapeutic target.
Gut and nasal microbiota also appear to play a role in PD. Alterations in the gut microbiome, including changes in short-chain fatty acid-producing bacteria, have been observed in PD patients. Notably, increases in Lactobacillus, Akkermansia, and Bifidobacterium have been reported in the gut, while the Lachnospiraceae family and Faecalibacterium genus are reduced.
Moreover, although still unconfirmed, nasal microbiota may contribute to neurodegeneration by traveling through the olfactory and trigeminal pathways, possibly initiating or exacerbating brain inflammation.
Evidence suggests that specific dietary patterns may influence PD risk and progression. Foods like dairy are associated with an increased risk of PD, while coffee, nicotine-containing vegetables (e.g., peppers and tomatoes), and high consumption of vegetables, nuts, and fish may reduce symptomatology.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Supportive Care
- 盲法
- Single (Outcomes Assessor)
盲法说明
The outcome assessors, including the study neurologist and researchers analyzing biological samples, will be blinded to the allocation of the patients. Patients will be instructed to keep this information confidential during their neurological evaluations. Before data analysis, the dataset will be anonymized a second time to perform a blind data analysis, so also investigators will be partially blinded.
入排标准
- 年龄范围
- 40 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •PD diagnosis according to international guidelines;
- •Age between 40 and 85 years;
- •Naive to medication or with a stable dosage of anti-Parkinson's therapy for at least two weeks;
- •Hoehn & Yahr stage ≤3;
- •Normal independent feeding;
- •Ability to complete informed consent;
- •Willingness to maintain the usual diet in the period between T0 and T1;
- •Willingness to maintain the usual diet if randomized to the control group in the T1-T2 period;
- •Willingness to make changes in their diet to follow a Mediterranean diet if randomized to the intervention group in the T1-T2 period;
- •Willingness to fill out questionnaires;
- •Willingness to provide blood samples during the study collection periods;
- •Willingness to provide stool samples during the study collection periods;
- •Willingness to fast (without food or drink except water, tea or coffee) at least 12 hours before each sample collection;
- •Willingness to discontinue taking supplements, probiotics, herbal or high- dose vitamins or minerals that could impact inflammation during the period between T0 and T1 and for the duration of the study protocol;
- •No medical and/or social conditions that could interfere with participation in a six-month interventional study.
排除标准
- •Atypical or secondary parkinsonism;
- •Underweight (<18.5);
- •Obesity (BMI>30);
- •Pregnancy or suspected pregnancy;
- •Normal assisted nutrition;
- •Enteral nutrition;
- •Chronic autoimmune diseases;
- •Chronic use of immunosuppressive drugs in the past year;
- •Chronic use of cytotoxic cancer drugs in the past year;
- •Major abdominal surgeries;
- •Concurrent participation in other interventional studies;
- •Intentional change in diet after PD diagnosis.
结局指标
主要结局
Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) I+II
时间窗: Baseline - 6 months
The primary outcome of this study is the mean (final - baseline) change in disease severity between the control and intervention groups at the end of the intervention, which will be assessed using the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) I+II score. Part I of the scale (13 items) investigates non-motor aspects of the disease, whilst part II (13 items) refers to motor aspects. The MDS-UPDRS will be performed at baseline and after 6 months. The scores in each item vary from 0 (normal) to 4(severe), Higher the score, the more severe the condition or symptom.
次要结局
- Immunophenotype(Baseline - 6 months)
- Intestinal and Nasal microbiota(Baseline - 6 months)
- Fecal metabolites(Baseline - 6 months)
- Urinary metabolites(Baseline - 6 months)
- Non-Motor Symptom Scale (NMSS)(Baseline - 6 months)
- Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS)(Baseline - 6 months)
- GSRS (Gastrointestinal Symptom Rating Scale)(Baseline - 6 months)
- The Pac-QoL (Patient Assessment of Constipation Quality of Life)(Baseline - 6 months)
- Diet adherence - MEDAS (Mediterranean Diet Adherence Screener)(Baseline - 6 months)
- Quality of life - SF-36 (36-Item Short Form Health Survey)(Baseline - 6 months)
- Body Mass Index (BMI)(Baseline - 6 months)
- Waist circumference(Baseline - 6 months)
- Daily Levodopa Equivalent Dose(Baseline - 6 months)
- Complete blood count with formula(Baseline - 6 months)
- Total Cholesterol(Baseline - 6 months)
- HDL Cholesterol(Baseline - 6 months)
- LDL Cholesterol(Baseline - 6 months)
- Triglycerides(Baseline - 6 months)
- Glycemia(Baseline - 6 months)
- GOT (transaminase)(Baseline - 6 months)
- GPT (transaminase)(Baseline - 6 months)
- Erythrocyte Sedimentation Rate(Baseline - 6 months)
- Gamma-glutamyl transferase(Baseline - 6 months)
- Creatinine(Baseline - 6 months)
- Azotemia(Baseline - 6 months)
- Uricemia(Baseline - 6 months)
- Erythrocyte Sedimentation Rate(Baseline - 6 months)
- Creatinine(Baseline - 6 months)
- Azotemia(Baseline - 6 months)
- Uricemia(Baseline - 6 months)
- Gamma-glutamyl transferase(Baseline - 6 months)
- Immunophenotype(Baseline - 6 months)
- Intestinal and Nasal microbiota(Baseline - 6 months)
- Fecal metabolites(Baseline - 6 months)
- LDL Cholesterol(Baseline - 6 months)
- Triglycerides(Baseline - 6 months)
- Glycemia(Baseline - 6 months)
- GOT (transaminase)(Baseline - 6 months)
- GPT (transaminase)(Baseline - 6 months)
- Non-Motor Symptom Scale (NMSS)(Baseline - 6 months)
- HDL Cholesterol(Baseline - 6 months)
- Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS)(Baseline - 6 months)
- GSRS (Gastrointestinal Symptom Rating Scale)(Baseline - 6 months)
- The Pac-QoL (Patient Assessment of Constipation Quality of Life)(Baseline - 6 months)
- Diet adherence - MEDAS (Mediterranean Diet Adherence Screener)(Baseline - 6 months)
- Quality of life - SF-36 (36-Item Short Form Health Survey)(Baseline - 6 months)
- Body Mass Index (BMI)(Baseline - 6 months)
- Waist circumference(Baseline - 6 months)
- Daily Levodopa Equivalent Dose(Baseline - 6 months)
- Complete blood count with formula(Baseline - 6 months)
- Total Cholesterol(Baseline - 6 months)
研究者
Franca Marino
Professor
Università degli Studi dell'Insubria