Clinical trial NCT06705517: Mediterranean Diet Effects on Parkinson's Disease
Official title: Mediterranean Diet Effects on Parkinson's Disease (MED-PARK): a Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Parkinson
Parkinson Disease
Parkinson Disease, Idiopathic
PARKINSON DISEASE (Disorder)
Keywords: Diet
Mediterranean Diet
Parkinson
Parkinson disease
MIND diet
plant based diet
unprocessed diet
Lead sponsor: Università degli Studi dell'Insubria
Sponsor class: OTHER
Collaborators: name: Associazione Parkinson Insubria (AsPI), Section of Varese
name: University of Piemonte Orientale
name: Universidade Nova de Lisboa
First posted: 2024-11-26
Enrollment: 44
Sex: ALL
Minimum age (years): 40
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is an interventional, non-pharmacological, superiority, randomized, controlled, single-center, masked study with two parallel groups.
Primary purpose: SUPPORTIVE_CARE

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 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 metabolomics, and diet adherence levels.

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.

Primary outcomes:
measure: Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) I+II
timeFrame: Baseline - 6 months
Secondary outcomes:
measure: Immunophenotype
timeFrame: Baseline - 6 months
measure: Intestinal and Nasal microbiota
timeFrame: Baseline - 6 months
measure: Fecal metabolites
timeFrame: Baseline - 6 months
measure: Non-Motor Symptom Scale (NMSS)
timeFrame: Baseline - 6 months
measure: Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS)
timeFrame: Baseline - 6 months
measure: GSRS (Gastrointestinal Symptom Rating Scale)
timeFrame: Baseline - 6 months
measure: The Pac-QoL (Patient Assessment of Constipation Quality of Life)
timeFrame: Baseline - 6 months
measure: Diet adherence - MEDAS (Mediterranean Diet Adherence Screener)
timeFrame: Baseline - 6 months
measure: Quality of life - SF-36 (36-Item Short Form Health Survey)
timeFrame: Baseline - 6 months
measure: Body Mass Index (BMI)
timeFrame: Baseline - 6 months
measure: Waist circumference
timeFrame: Baseline - 6 months
measure: Daily Levodopa Equivalent Dose
timeFrame: Baseline - 6 months
measure: Complete blood count with formula
timeFrame: Baseline - 6 months
measure: Total Cholesterol
timeFrame: Baseline - 6 months
measure: HDL Cholesterol
timeFrame: Baseline - 6 months
measure: LDL Cholesterol
timeFrame: Baseline - 6 months
measure: Triglycerides
timeFrame: Baseline - 6 months
measure: Glycemia
timeFrame: Baseline - 6 months
measure: GOT (transaminase)
timeFrame: Baseline - 6 months
measure: GPT (transaminase)
timeFrame: Baseline - 6 months
measure: Gamma-glutamyl transferase
timeFrame: Baseline - 6 months
measure: Erythrocyte Sedimentation Rate
timeFrame: Baseline - 6 months
measure: Creatinine
timeFrame: Baseline - 6 months
measure: Azotemia
timeFrame: Baseline - 6 months
measure: Uricemia
timeFrame: Baseline - 6 months
Other outcomes:
Locations:
city: Varese
country: Italy
facility: Centre for Research in Medical Pharmacology
Study officials:
affiliation: Università degli studi dell Insubria
name: Marco Cosentino, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Università degli studi dell Insubria
name: Franca Marino, M.Sc., PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Università degli studi dell Insubria
name: Elenamaria Pirovano, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.