Parkinson's Disease (PD)PRIME_2025NCT07097103
Parkinson's Research In Metagenomic Early Stage Biomarkers
A study testing Mediterranean Diet Intervention and Intensive Physical Activity Intervention in people with Parkinson's Disease (PD), run by IRCCS San Raffaele Roma at 2 sites in Italy.
Trial 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… Read more about this study
- Who is it for?
- Ages 35 to 80 years
- Conditions the study is for
- Parkinson's Disease (PD)
- What is being tested?
- Mediterranean Diet Intervention and Intensive Physical Activity Intervention
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 80 participants
- Where
- 2 sitesItaly
- Study dates
- 1 Sep 2026to 31 Jul 2029
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 35 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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;
Show all 14Show fewer
- 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.
Who cannot join
- 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;
Show all 28Show fewer
- 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.
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Italy2 sites
Casa di Cura San Raffale Cassino
Cassino, Frosinone, 03043
Maria Francesca De Pandis, MD, PhD, 0776394740 ext. 0039, maria.depandis@sanraffale.it
Maria Gaglione, maria.gaglione@sanraffaele.it
IRCCS San Raffale Roma
Rome, Lazio, 00166
Fabrizio Stocchi, MD, PhD, 0652252311 ext. 0039, fabrizio.stocchi@sanraffaele.it
Alice Fognani, 3470594253, alice.fognani@uniroma5.it
About this study
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
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.
Read the 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).
- Conditions
- Parkinson's Disease (PD)
- Being tested
- Mediterranean Diet Intervention, Intensive Physical Activity Intervention, Control
- Keywords
- Physical activity, Mediterranean Diet, Pilot study, Microbiome, Parkinson's disease
- Medical subject headings
- Motor Activity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Mediterranean Diet InterventionBehavioural
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.
Intensive Physical Activity InterventionBehavioural
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.
ControlOther
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.
| Study group | Role | What they receive |
|---|---|---|
| Mediterranean Diet Intervention (Group A) | Experimental | Participants receive a structured Mediterranean Diet intervention, including personalized counseling, meal plans, educational sessions and monitoring. Receives: Behavioral: Mediterranean Diet Intervention |
| Intensive Physical Activity Intervention (Group B) | Experimental | Participants engage in a supervised structured physical activity program. Receives: Behavioral: Intensive Physical Activity Intervention |
| Mediterranean Diet + Intensive Physical Activity Combined Intervention (Group C=A+B) | Experimental | Participants will receive both dietary and physical activity interventions. Receives: Behavioral: Mediterranean Diet Intervention; Behavioral: Intensive Physical Activity Intervention |
| Controls (Group D) | Active comparator | Participants continue their usual Parkinson's disease treatments according to clinical guidelines, without any additional specific dietary or exercise interventions provided by the study. Receives: Other: Control |
What is being measured
The primary outcome is the main question the study is designed to answer.
Alpha Diversity of the fecal microbiota.
Changes in fecal microbiota alpha diversity, a measure of the richness and evenness of microbial species within a sample, will be assessed.
Measured: Baseline (Week 0); End of intervention (Week 24); First Follow-up (Week 36); Second Follow-up (Week 48)
Beta Diversity of the fecal microbiota
Changes in fecal microbiota beta diversity, refers to the degree of difference in microbial community composition between different fecal samples, will be assessed.
Measured: 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
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.
Measured: Baseline (Week 0); End of intervention (Week 24); First Follow-up (Week 36); Second Follow-up (Week 48)
Fecal Microbial relative quantification
Changes in relative quantification
Measured: Baseline (Week 0); End of intervention (Week 24); First Follow-up (Week 36); Second Follow-up (Week 48)
Secondary outcomes (4)
Intestinal Inflammation
Changes in fecal calprotectin (a valid and non-invasive marker of mucosal inflammation) will be assessed using enzyme-linked immunosorbent assay (ELISA).
Measured: Baseline (Week 0); End of intervention (Week 24); First Follow-up (Week 36); Second Follow-up (Week 48)
Intestinal Permeability
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.
Measured: 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.
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).
Measured: 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.
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.
Measured: Baseline (Week 0); End of intervention (Week 24); First Follow-up (Week 36); Second Follow-up (Week 48)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jul 2025
- Study start1 Sep 2026 (estimated)
- Primary completion11 Jul 2029 (estimated)
- Study completion31 Jul 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Parkinson's Disease (PD)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Factorial
- Model description
- It's a 2x2 factorial, randomized, controlled, non-pharmacological intervention pilot study
- Masking
- None (open label)
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- IRCCS San Raffaele Roma
- Sponsor type
- University, hospital or other
- Collaborators
- San Raffaele Telematic University, University of Urbino "Carlo Bo", Northwestern University
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07097103
- Sponsor's protocol ID
- RP 340/SR/25
- Acronym
- PRIME_2025
- Status last verified
- Jul 2026
- First submitted
- 30 Jun 2025
- Last updated
- 30 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
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 study (PRIME study). Front Aging Neurosci. 2026 Mar 25;18:1743490. doi: 10.3389/fnagi.2026.1743490. eCollection 2026.
PubMed 41959663
Study at a glance
From the registry record, last updated by the sponsor on 30 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT07097103
- Acronym / sponsor ID
- PRIME_2025 / RP 340/SR/25
- Conditions
- Parkinson's Disease (PD)
- Keywords
- Physical activity, Mediterranean Diet, Pilot study, Microbiome, Parkinson's disease
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- IRCCS San Raffaele RomaUniversity, hospital or other
- Collaborators
- San Raffaele Telematic University, University of Urbino "Carlo Bo", Northwestern University
- Study start
- 1 Sep 2026 (estimated)
- Primary completion
- 11 Jul 2029 (estimated)
- Study completion
- 31 Jul 2029 (estimated)
- First posted
- 31 Jul 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Number of arms
- 4
- Model description
- It's a 2x2 factorial, randomized, controlled, non-pharmacological intervention pilot study
| Arm | Type | Receives |
|---|---|---|
| Mediterranean Diet Intervention (Group A) | Experimental | Behavioral: Mediterranean Diet InterventionParticipants receive a structured Mediterranean Diet intervention, including personalized counseling, meal plans, educational sessions and monitoring. |
| Intensive Physical Activity Intervention (Group B) | Experimental | Behavioral: Intensive Physical Activity InterventionParticipants engage in a supervised structured physical activity program. |
| Mediterranean Diet + Intensive Physical Activity Combined Intervention (Group C=A+B) | Experimental | Behavioral: Mediterranean Diet Intervention, Behavioral: Intensive Physical Activity InterventionParticipants will receive both dietary and physical activity interventions. |
| Controls (Group D) | Active comparator | Other: ControlParticipants continue their usual Parkinson's disease treatments according to clinical guidelines, without any additional specific dietary or exercise interventions provided by the study. |
Who may qualify
- Ages
- 35 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- 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;
Key exclusion criteria (28 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Mediterranean Diet InterventionParticipants 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. | Behavioural | Mediterranean Diet + Intensive Physical Activity Combined Intervention (Group C=A+B), Mediterranean Diet Intervention (Group A) |
| Intensive Physical Activity InterventionParticipants 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. | Behavioural | Intensive Physical Activity Intervention (Group B), Mediterranean Diet + Intensive Physical Activity Combined Intervention (Group C=A+B) |
| ControlParticipants 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. | Other | Controls (Group D) |
Primary outcome
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
4 secondary outcomes
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)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jul 2026.
- Derived from this study: PubMed 41959663Fognani 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 study (PRIME study). Front Aging Neurosci. 2026 Mar 25;18:1743490. doi: 10.3389/fnagi.2026.1743490. eCollection 2026.
- Individual participant dataSharing planned: No
Related trials for Parkinson's Disease (PD)
Active, not recruitingPhase 2
A Study to Evaluate Efficacy, Safety and Tolerability of Hydroxychloroquine in Subjects With Parkinson's Disease
Parkinson&Amp;#39;s Disease
Recruiting
Prevention-in-PD-Study
Parkinson's Disease (PD)
Recruiting
Effect of Physical Activity on the Course of Parkinson's Disease in Patients With Bilateral DBS-STN Stimulation.
Parkinson Disease, Deep Brain Stimulation
RecruitingPhase 2
RE104 Safety and Efficacy Study in Adjustment Disorder in Cancer and Other Medical Illnesses
Adjustment Disorder
Not yet recruiting
Closed-Loop Therapeutic Refinement Using Local Field Potentials in Parkinson's Disease
Parkinson's Disease (PD)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Mediterranean Diet Intervention and Intensive Physical Activity Intervention in people with Parkinson's Disease (PD), run by IRCCS San Raffaele Roma at 2 sites in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 30 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Alice Fognani (+39 0652253440, alice.fognani@uniroma5.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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)). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07097103, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jul 2026.