Parkinson's Disease (PD)
Conditions
Keywords
Physical activity, Mediterranean Diet, Pilot study, Microbiome, Parkinson's disease
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).
Interventions
BEHAVIORALMediterranean 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 during a pre-baseline period of at least 4 weeks, then switch to the Mediterranean plan under the supervision of a nutritionist.
BEHAVIORALIntensive 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 or more days per week. Adherence will be monitored during in-person sessions and through wearable devices for activity tracking.
OTHERControl
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.
Sponsors
IRCCS San Raffaele Roma
San Raffaele Telematic University
University of Urbino "Carlo Bo"
Northwestern University
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
PREVENTION
Masking
NONE
Intervention model description
It's a 2x2 factorial, randomized, controlled, non-pharmacological intervention pilot study
Eligibility
Sex/Gender
ALL
Age
35 Years to 80 Years
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Alpha Diversity of the fecal microbiota. | 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 | 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 | 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 | Baseline (Week 0); End of intervention (Week 24); First Follow-up (Week 36); Second Follow-up (Week 48) | Changes in relative quantification |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Intestinal Inflammation | Baseline (Week 0); End of intervention (Week 24); First Follow-up (Week 36); Second Follow-up (Week 48) | Changes in fecal calprotectin (a valid and non-invasive marker of mucosal inflammation) will be assessed using enzyme-linked immunosorbent assay (ELISA). |
| Intestinal Permeability | Baseline (Week 0); End of intervention (Week 24); First Follow-up (Week 36); Second Follow-up (Week 48) | Changes in fecal zonulin will be assessed using enzyme-linked immunosorbent assay (ELISA). The unit for measuring zonulin in stool samples is nanograms per milliliter (ng/mL). The Protein Zonulin is a very important indicator for leaky gut. |
| 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) | To evaluate the effect of the combined diet and physical activity intervention on extracellular vesicles (EVs), EVs will be isolated from saliva and plasma by serial ultracentrifugation and size-exclusion chromatography. EV concentration and size distribution will be determined by nanoparticle tracking analysis (NTA). |
| 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) | Extracellular Vesicles (EVs)-associated proteins (CD63, CD9, α-synuclein, BDNF, L1CAM, and CD56) will be quantified by dot blot and confirmed by fluorescent NTA and/or cytofluorimetric analysis. |
Countries
Italy
Contacts
CONTACTAlice Fognani
CONTACTLucia Gatta, PhD
Outcome results
None listed