A 2x2 Factorial Randomized Controlled Non-pharmacological Interventional Multicenter Pilot Study on the Influence of the Mediterranean Diet and Physical Exercise on the Microbiome of Patients With Parkinson's Disease
Trial Snapshot
- Phase
- Not Applicable
- Status
- Not yet recruiting
- Sponsor
- Enrollment
- 80
- Locations
- 2
- Primary Endpoint
- Alpha Diversity of the fecal microbiota.
Study Overview
Brief Summary
This 2x2 factorial, randomized, controlled pilot study aims to identify a specific microbiota pattern, which could constitute a biomarker of Parkinson's disease, and to evaluate whether specific pathotypes can be associated with different stages of the disease; furthermore, the investigators are committed to evaluating how and to what extent the changes induced by a personalized nutritional intervention combined with physical exercise affect the symptoms and quality of life of patients.
Detailed Description
The study will last 60 months, and the following activities are planned:
- Study presentation, selection and enrollment of patients;
- Evaluation of patients' health and nutritional status, including collection of physiological, pathological, and pharmacological history;
- Randomization of patients into four groups;
- Sample collection and storage;
- Microbiome analysis;
- Evaluation of motor and non-motor symptoms using clinical tests and rating scales at baseline (T0), at six months (T1) after treatment initiation, and at three and six months post-intervention (FU1 and FU2, respectively).
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Factorial
- Primary Purpose
- Prevention
- Masking
- None
Eligibility Criteria
- Ages
- 35 Years to 80 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Diagnosis of Parkinson's disease according to United Kingdom (UK) Parkinson's Disease Society Brain Bank criteria;
- •aged 35-80 years;
- •Hoehn & Yahr stage > 1 and < 3 in the clinical "ON" state;
- •MoCA score ≥17.54;
- •MMSE ≥24;
- •Stable dopaminergic midication regimen for ≥ 4 weeks;
- •Ability to interact with the research team and provide informed consent in Italian;
- •Suitable to physical exercise;
- •Able to walk unassisted (no walking aids);
- •Willingness and ability to comply with all study procedures;
- •Willingness to maintain usual diet during a ≥ 4-week pre-baseline period;
- •Willingness to switch to a Mediterranean-style diet during the intervention;
- •Ability to provide stool samples at each collection timepoint;
- •Willing to avoid strenuous exercise and alcohol for 24 hours prior to each visits.
Exclusion Criteria
- •Pre-existing psychiatric disorders;
- •Atypical or secondary Parkinsonism;
- •Presence of pacemakers or other subcutaneous electronic devices;
- •Any other neurological or neurodegenerative disorders;
- •Moderate to severe cognitive decline;
- •Beck Depression Inventory-II (BDI-II)] score ≥28;
- •Dementia diagnosis;
- •Thyroid dysfunctions;
- •Type1 Diabetes Mellitus;
- •Type 2 diabetes mellitus with HbA₁c ≥ 8% or on insulin therapy;
- •Acute diseases;
- •Active Neoplasia;
- •IBD or IBS;
- •Celiac disease;
- •History of major gastrointestinal surgery or acute GI conditions (e.g., gastroenteritis) within the past 3-6 months;
- •Chronic corticosteroid therapy;
- •Use of proton pump inhibitors within the past 30 days;
- •Acute, antibiotic-resistant infections;
- •Antibiotic intake within the past 30 days;
- •Prebiotic/probiotic supplement use in the past 30 days;
- •Prolonged intake of anxiolytic drugs, antidepressants, antipsychotics, cognitive stimulants, and analogs in the past 3 months;
- •Underweight (BMI <18.5);
- •History of deep brain stimulation (DBS) surgery;
- •Pregnancy or lactation;
- •Regular use of enemas or suppositories to alleviate constipation;
- •Use of experimental products in the 3 months prior to the screening visit
- •Patients who, for medical reasons, are required to follow special dietary regimens that could interfere with the adoption or effectiveness of the Mediterranean model;
- •Vegan/Vegetarian diet or any other dietary behaviour that excludes one or more of the typical food groups of the Mediterranean model.
Arms & Interventions
Controls (Group D)
Participants continue their usual Parkinson's disease treatments according to clinical guidelines, without any additional specific dietary or exercise interventions provided by the study.
Intervention: Control (Other)
Mediterranean Diet Intervention (Group A)
Participants receive a structured Mediterranean Diet intervention, including personalized counseling, meal plans, educational sessions and monitoring.
Intervention: Mediterranean Diet Intervention (Behavioral)
Intensive Physical Activity Intervention (Group B)
Participants engage in a supervised structured physical activity program.
Intervention: Intensive Physical Activity Intervention (Behavioral)
Mediterranean Diet + Intensive Physical Activity Combined Intervention (Group C=A+B)
Participants will receive both dietary and physical activity interventions.
Intervention: Mediterranean Diet Intervention (Behavioral)
Mediterranean Diet + Intensive Physical Activity Combined Intervention (Group C=A+B)
Participants will receive both dietary and physical activity interventions.
Intervention: Intensive Physical Activity Intervention (Behavioral)
Outcomes
Primary Outcomes
Alpha Diversity of the fecal microbiota.
Time Frame: Baseline (Week 0); End of intervention (Week 24); First Follow-up (Week 36); Second Follow-up (Week 48)
Changes in fecal microbiota alpha diversity, a measure of the richness and evenness of microbial species within a sample, will be assessed.
Beta Diversity of the fecal microbiota
Time Frame: Baseline (Week 0); End of intervention (Week 24); First Follow-up (Week 36); Second Follow-up (Week 48)
Changes in fecal microbiota beta diversity, refers to the degree of difference in microbial community composition between different fecal samples, will be assessed.
Enterobacteriaceae species abundance across Parkinson's disease stage
Time Frame: Baseline (Week 0); End of intervention (Week 24); First Follow-up (Week 36); Second Follow-up (Week 48)
Changes in fecal microbial composition will be assessed. Specifically, we will measure the relative abundance of Enterobacteriaceae species and pathotypes across different stages of Parkinson's disease.
Fecal Microbial relative quantification
Time Frame: Baseline (Week 0); End of intervention (Week 24); First Follow-up (Week 36); Second Follow-up (Week 48)
Changes in relative quantification
Secondary Outcomes
- Intestinal Inflammation(Baseline (Week 0); End of intervention (Week 24); First Follow-up (Week 36); Second Follow-up (Week 48))
- Intestinal Permeability(Baseline (Week 0); End of intervention (Week 24); First Follow-up (Week 36); Second Follow-up (Week 48))
- Changes in extracellular vesicle concentration (particles/mL) in saliva and plasma will be assessed.(Baseline (Week 0); End of intervention (Week 24); First Follow-up (Week 36); Second Follow-up (Week 48))
- Changes in protein marker expression in saliva and plasma.(Baseline (Week 0); End of intervention (Week 24); First Follow-up (Week 36); Second Follow-up (Week 48))