Parkinson's Research In Metagenomic Early Stage Biomarkers

Official title

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

Overview

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).

Interventions

• Behavioral Mediterranean Diet Intervention
  Participants will follow a personalized diet plan over 24 weeks, based on the guidelines of the Mediterranean diet and defined according to their needs and the state of the disease; no food category will be excluded a priori. Individualized nutritional counseling and support materials (weekly meal plans, sample recipes, portion guides) will be provided by a qualified nutritionist. Adherence to the Mediterranean diet will be monitored periodically. Participants will maintain their usual diet duri
• Behavioral Intensive Physical Activity Intervention
  Participants will perform exercise, over 24 weeks, according to WHO recommendations for adults, including those aged ≥ 64 years, to achieve at least 150-300 minutes of moderate-intensity aerobic physical activity, or at least 75-100 minutes of vigorous-intensity aerobic physical activity, or an equivalent combination of moderate and vigorous activity during the week. The WHO 2020 also recommend moderate-intensity or greater muscle-strengthening exercises involving alla major muscle groups for 2
• Other Control
  Participants will continue their usual medical management for early Parkinson's disease according to current clinical guidelines, without any additional dietary or exercise interventions provided by the study, and will be monitored through standard follow-up visits but will not receive any study-specific dietary or physical activity programs.

Primary outcome measures

• 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)]
• 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)]
• 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)]
• Fecal Microbial relative quantification [Time frame: Baseline (Week 0); End of intervention (Week 24); First Follow-up (Week 36); Second Follow-up (Week 48)]

Secondary outcome measures (4)

• Intestinal Inflammation [Time frame: Baseline (Week 0); End of intervention (Week 24); First Follow-up (Week 36); Second Follow-up (Week 48)]
• Intestinal Permeability [Time frame: 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. [Time frame: 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. [Time frame: Baseline (Week 0); End of intervention (Week 24); First Follow-up (Week 36); Second Follow-up (Week 48)]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Factorial

Masking

Open label

Primary purpose

Prevention

Study locations

Italy · 2 centers

• Casa di Cura San Raffale Cassino — Cassino
• IRCCS San Raffale Roma — Rome

Publications

• Fognani A, Rotondo R, Savo Sardaro ML, de Iure A, Gaglione M, Casali M, Leonardi L, Radicati FG, Vacca L, Guescini M, Zeppa SD, Gatta L, Stocchi F, Picconi B, De Pandis MF. Effects of combined Mediterranean diet and physical activity intervention on the gut microbiome and disease progression in individuals with Parkinson's disease: study protocol for a multicenter, randomized controlled pilot stud PMID 41959663

Identifiers

NCT: NCT07097103 · RP 340/SR/25

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗