Mediterranean Diet Effects on Parkinson's Disease

NCT ID: NCT06705517

Last Updated: 2025-07-11

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 44 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-01-17
• Study Completion Date: 2026-09-30

Brief Summary

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.

Detailed Description

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.

The MD, a plant-based diet rich in vegetables, fruits, whole grains, and healthy fats like olive oil, has been linked to numerous health benefits, including improved cognitive function, cardiovascular health, and a reduced risk of developing PD.

Studies show that a high-fiber diet can positively impact α-synuclein aggregation and microglial activation. Adherence to the MD may lower PD risk by up to 26%, slow disease progression, and improve both motor and non-motor symptoms. In contrast to pharmacological treatments, the MD has minimal side effects and could address several unmet needs in PD management, particularly in slowing disease progression and reducing comorbidities such as dementia.

This six-month randomized controlled trial aims to explore whether strict adherence to the MD can stabilize or slow the progression of motor and non-motor symptoms in PD patients. It will also investigate the impact of the MD on the immune system, gut and nasal microbiota, and fecal metabolomics, making it the first trial to assess these factors together. The study's primary goal is to determine the benefits of MD adherence on symptom management while also exploring correlations between immune function, microbiota composition, fecal and urinary metabolomics, and diet adherence levels.

Conditions

Parkinson; Parkinson Disease; Parkinson Disease, Idiopathic; PARKINSON DISEASE (Disorder)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: SUPPORTIVE_CARE
• Blinding Strategy: SINGLE

Study Groups

Intervention group (standard of care + MD)

The intervention group will participate in a six-month program aimed at promoting adherence to the MD. At the start, participants will be given a physical booklet outlining foods to prioritize and avoid. They will also receive monthly recipes featuring seasonal ingredients. In addition, cooking classes will be offered, with caregiver involvement encouraged.

Group Type: EXPERIMENTAL

Mediterranean Diet

Intervention Type: BEHAVIORAL

The MD emphasizes a plant-based approach, with a high consumption of vegetables, fruits, whole grains, legumes, and nuts, alongside moderate amounts of fish, seafood, and dairy, while limiting meat, particularly red and processed varieties. Olive oil serves as the main fat source in the diet. In the case of this study participants will also be instructed to limit dairy intake, that although traditionally part of the MD, might exacerbate disease symptomatology in PD patients, likely due to the urate lowering effect of dairy.

Control group (standard of care)

The control group will be asked to maintain their current dietary habits and usual standard care. They will undergo the same routine examinations and check-ups as the intervention group.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Mediterranean Diet

The MD emphasizes a plant-based approach, with a high consumption of vegetables, fruits, whole grains, legumes, and nuts, alongside moderate amounts of fish, seafood, and dairy, while limiting meat, particularly red and processed varieties. Olive oil serves as the main fat source in the diet. In the case of this study participants will also be instructed to limit dairy intake, that although traditionally part of the MD, might exacerbate disease symptomatology in PD patients, likely due to the urate lowering effect of dairy.

Intervention Type: BEHAVIORAL

Other Intervention Names

Dietary intervention

Eligibility Criteria

Inclusion Criteria

1. PD diagnosis according to international guidelines;

2. Age between 40 and 85 years;

3. Naive to medication or with a stable dosage of anti-Parkinson's therapy for at least two weeks;

4. Hoehn & Yahr stage ≤3;

5. Normal independent feeding;

6. Ability to complete informed consent;

7. Willingness to maintain the usual diet in the period between T0 and T1;

8. Willingness to maintain the usual diet if randomized to the control group in the T1-T2 period;

9. Willingness to make changes in their diet to follow a Mediterranean diet if randomized to the intervention group in the T1-T2 period;

10. Willingness to fill out questionnaires;

11. Willingness to provide blood samples during the study collection periods;

12. Willingness to provide stool samples during the study collection periods;

13. Willingness to fast (without food or drink except water, tea or coffee) at least 12 hours before each sample collection;

14. 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;

15. No medical and/or social conditions that could interfere with participation in a six-month interventional study.

Exclusion Criteria

1. Atypical or secondary parkinsonism;

2. Underweight (<18.5);

3. Obesity (BMI>30);

4. Pregnancy or suspected pregnancy;

5. Normal assisted nutrition;

6. Enteral nutrition;

7. Chronic autoimmune diseases;

8. Chronic use of immunosuppressive drugs in the past year;

9. Chronic use of cytotoxic cancer drugs in the past year;

10. Major abdominal surgeries;

11. Concurrent participation in other interventional studies;

12. Intentional change in diet after PD diagnosis.

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Associazione Parkinson Insubria (AsPI), Section of Varese

UNKNOWN

Sponsor Role: collaborator

University of Piemonte Orientale

UNKNOWN

Sponsor Role: collaborator

Universidade Nova de Lisboa

OTHER

Sponsor Role: collaborator

Università degli Studi dell'Insubria

OTHER

Sponsor Role: lead

Responsible Party

Franca Marino

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Marco Cosentino, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Università degli studi dell Insubria

Franca Marino, M.Sc., PhD

Role: PRINCIPAL_INVESTIGATOR

Università degli studi dell Insubria

Elenamaria Pirovano, MD

Role: PRINCIPAL_INVESTIGATOR

Università degli studi dell Insubria

Locations

Centre for Research in Medical Pharmacology

Varese, Varese, Italy

Site Status: RECRUITING

Countries

Italy

Central Contacts

Marco Cosentino, MD, PhD

Role: CONTACT

marco.cosentino@uninsubria.it

0332217427 ext. +39

Franca Marino, M.Sc., PhD

Role: CONTACT

franca.marino@uninsubria.it

0332217427 ext. +39

Facility Contacts

Marco Cosentino, MD, PhD

Role: primary

marco.cosentino@uninisubria.it

+39 0332217427

Franca Marino, M.Sc., PhD

Role: backup

franca.marino@uninsubria.it

References

Kustrimovic N, Rasini E, Legnaro M, Bombelli R, Aleksic I, Blandini F, Comi C, Mauri M, Minafra B, Riboldazzi G, Sanchez-Guajardo V, Marino F, Cosentino M. Dopaminergic Receptors on CD4+ T Naive and Memory Lymphocytes Correlate with Motor Impairment in Patients with Parkinson's Disease. Sci Rep. 2016 Sep 22;6:33738. doi: 10.1038/srep33738.

Reference Type: BACKGROUND

PMID: 27652978 (View on PubMed)

Kustrimovic N, Comi C, Magistrelli L, Rasini E, Legnaro M, Bombelli R, Aleksic I, Blandini F, Minafra B, Riboldazzi G, Sturchio A, Mauri M, Bono G, Marino F, Cosentino M. Parkinson's disease patients have a complex phenotypic and functional Th1 bias: cross-sectional studies of CD4+ Th1/Th2/T17 and Treg in drug-naive and drug-treated patients. J Neuroinflammation. 2018 Jul 12;15(1):205. doi: 10.1186/s12974-018-1248-8.

Reference Type: BACKGROUND

PMID: 30001736 (View on PubMed)

Pirovano E, Marino F, Rossi E, Gennari A, Rasini E, Uslenghi M, Figueira I, Iacoviello L, Ferrari M, Cosentino M. Modified Mediterranean diet effects on Parkinson's disease (MED-PARK): a single-centre randomised controlled trial protocol. BMJ Open. 2025 Oct 5;15(10):e101946. doi: 10.1136/bmjopen-2025-101946.

Reference Type: DERIVED

PMID: 41047258 (View on PubMed)

Other Identifiers

MED-PARK

Identifier Type: -

Identifier Source: org_study_id