Mediterranean Diet in Parkinson's Disease (NCT07187739)

Overview

This clinical trial investigates whether Mediterranean diet adherence can improve nutritional status, gut microbiome composition, and clinical outcomes in Parkinson's disease patients. The study targets the gut-brain axis as a modifiable pathway for both motor and non-motor symptoms in PD. Parkinson's disease is increasingly recognized as having significant gut involvement, with the Mediterranean diet potentially addressing multiple pathophysiological mechanisms through its anti-inflammatory and prebiotic properties.

Trial Details

| Parameter | Value |
|-----------|-------|
| NCT Number | NCT07187739 |
| Phase | Phase 2 |
| Status | Recruiting |
| Sponsor | Ankara University |
| Intervention | Mediterranean Diet + Standard Care vs. Standard Care Alone |
| Duration | 24 weeks |
| Sample Size | Approximately 60 participants |
| Primary Endpoint | Change in Mediterranean Diet Adherence Score (MEDAS) |
| Secondary Endpoints | MDS-UPDRS, gut microbiome composition, inflammatory markers |

Background

Parkinson's Disease and Nutrition

Parkinson's disease (PD) is the second most common neurodegenerative disorder, affecting approximately 10 million people worldwide. Beyond the hallmark motor symptoms (bradykinesia, resting tremor, rigidity), patients experience a range of non-motor symptoms including constipation, depression, sleep disorders, and cognitive impairment. Growing evidence suggests that nutritional factors play a significant role in disease pathogenesis and progression[@perez2021][@braak2006].

Overview

This clinical trial investigates whether Mediterranean diet adherence can improve nutritional status, gut microbiome composition, and clinical outcomes in Parkinson's disease patients. The study targets the gut-brain axis as a modifiable pathway for both motor and non-motor symptoms in PD. Parkinson's disease is increasingly recognized as having significant gut involvement, with the Mediterranean diet potentially addressing multiple pathophysiological mechanisms through its anti-inflammatory and prebiotic properties.

Trial Details

| Parameter | Value |
|-----------|-------|
| NCT Number | NCT07187739 |
| Phase | Phase 2 |
| Status | Recruiting |
| Sponsor | Ankara University |
| Intervention | Mediterranean Diet + Standard Care vs. Standard Care Alone |
| Duration | 24 weeks |
| Sample Size | Approximately 60 participants |
| Primary Endpoint | Change in Mediterranean Diet Adherence Score (MEDAS) |
| Secondary Endpoints | MDS-UPDRS, gut microbiome composition, inflammatory markers |

Background

Parkinson's Disease and Nutrition

Parkinson's disease (PD) is the second most common neurodegenerative disorder, affecting approximately 10 million people worldwide. Beyond the hallmark motor symptoms (bradykinesia, resting tremor, rigidity), patients experience a range of non-motor symptoms including constipation, depression, sleep disorders, and cognitive impairment. Growing evidence suggests that nutritional factors play a significant role in disease pathogenesis and progression[@perez2021][@braak2006].

Key nutritional concerns in PD include:

• Weight loss and malnutrition: Common in PD patients, affecting up to 50% of individuals
• Gut dysfunction: Constipation is one of the earliest and most prevalent non-motor symptoms
• Medication interactions: Protein timing affects levodopa absorption
• Oxidative stress: Increased in PD brains and potentially modifiable through diet
• Neuroinflammation: Chronic neuroinflammation contributes to neurodegeneration

Mediterranean Diet Overview

The Mediterranean diet is characterized by high consumption of:

• Olive oil: Primary fat source, rich in monounsaturated fatty acids and polyphenols
• Vegetables and fruits: Abundant plant-based foods
• Whole grains: Complex carbohydrates and fiber
• Legumes: Beans, lentils, chickpeas
• Nuts and seeds: Healthy fats and protein
• Fish and seafood: Omega-3 fatty acids
• Moderate wine: Optional, with meals
• Limited red meat and processed foods

Mediterranean Diet in Neurodegeneration

Multiple mechanisms link Mediterranean diet adherence to neuroprotection[@sufficient2021][@angelova2020]:

Gut-Brain Axis in PD

The gut-brain axis is increasingly recognized as a key player in PD pathogenesis[@braak2006][@perez2021]. This bidirectional communication system involves neural, endocrine, immune, and metabolic pathways connecting the gastrointestinal tract with the central nervous system. In PD, pathological alpha-synuclein aggregates are thought to originate in the gut and propagate via the vagus nerve to the brain, representing one of the earliest events in disease development[@chen2018].

Key aspects of gut-brain axis involvement in PD include:

• α-Synuclein propagation: Gut vagus nerve may transmit α-synuclein to brain
• Neuroinflammation: Gut-derived inflammatory signals cross the blood-brain barrier
• Microbiota alterations: PD patients show distinct gut microbiome signatures
• Leaky gut: Increased intestinal permeability allows bacterial products to enter circulation
• SCFA deficiency: Short-chain fatty acid production is reduced in PD patients

Trial Design

Study Population

Inclusion Criteria

• Parkinson's disease diagnosis (UK Brain Bank criteria)
• Age 40-80 years
• Mild-to-moderate disease severity (Hoehn-Yahr stage 1-3)
• Stable PD medications for ≥4 weeks
• Able to follow Mediterranean diet instructions
• Provide informed consent
• Willing to complete dietary assessments

• Current Mediterranean diet adherent (MEDAS score ≥10)
• Significant gastrointestinal disorders (IBD, celiac disease)
• Severe cognitive impairment (MMSE <24)
• Active hallucinations or psychosis
• Uncontrolled medical conditions (diabetes, heart failure)
• Recent dietary changes or supplements
• Food allergies preventing Mediterranean diet adherence

Endpoints

Primary

• Change in Mediterranean Diet Adherence Score (MEDAS) at 24 weeks

• Change in MDS-UPDRS total score
• Change in MDS-UPDRS motor score (Part 3)
• Change in non-motor symptoms (MDS-UPDRS Part 1)
• Gastrointestinal symptom score (GSRS)
• Fecal microbiome composition (alpha and beta diversity)
• Inflammatory markers (CRP, IL-6, TNF-α)
• Quality of life (PDQ-39)
• Nutritional status (MNA score)
• Safety and tolerability assessments

Assessment Schedule

| Visit | Timing | Assessments |
|-------|--------|-------------|
| Screening | Week -2 to 0 | MEDAS, medical history, physical exam |
| Baseline | Week 0 | MEDAS, MDS-UPDRS, PDQ-39, blood, stool |
| Week 8 | Week 8 | MEDAS, safety assessment |
| Week 16 | Week 16 | MEDAS, MDS-UPDRS, PDQ-39 |
| Week 24 | Week 24 | All primary and secondary endpoints |
| Follow-up | Week 28 | Safety assessment, adverse events |

Clinical Translation

Biomarker Connections

Gut Health Markers

• Fecal microbiome composition (alpha and beta diversity)
• Inflammatory markers (CRP, IL-6, TNF-α)
• Gut permeability markers (zonulin)
• Short-chain fatty acid levels (butyrate, propionate, acetate)
• Fecal calprotectin

• CSF inflammatory markers
• α-Synuclein seeding assays
• Neurofilament light chain (NfL)

• Mediterranean Diet Adherence Score (MEDAS)
• Mini Nutritional Assessment (MNA)
• Vitamin D levels
• Omega-3 index
• Antioxidant capacity

Mechanistic Pathways

Patient Impact

Potential Benefits

• Non-pharmacological intervention for PD symptoms
• Addresses root cause through gut-brain axis
• Minimal side effects compared to medications
• May improve both motor and non-motor symptoms
• Potential for disease-modifying effects
• Cardiovascular protection
• Cognitive benefits

• Requires significant dietary changes
• Long-term maintenance needed for sustained benefits
• Cultural adaptation may be difficult
• Variable individual response
• Need for dietary counseling support
• Cost of Mediterranean diet components

Competitive Landscape

| Intervention | Mechanism | Stage | Status |
|--------------|-----------|-------|--------|
| Mediterranean Diet (NCT07187739) | Gut microbiome modulation | Phase 2 | Recruiting |
| Probiotic (NCT05568498) | Gut microbiome modulation | Phase 2 | Recruiting |
| Calorie restriction | Metabolic modulation | Observational | Various |
| Ketogenic diet | Metabolic modulation | Phase 2 | Recruiting |
| Standard care | - | Standard | Approved |

Research Context

Supporting Evidence

The trial builds on substantial preclinical and clinical evidence:

Preclinical Studies

• Mediterranean diet components reduce neuroinflammation in animal models
• Olive oil polyphenols protect dopaminergic neurons
• Omega-3 fatty acids reduce alpha-synuclein aggregation
• Fiber supplementation increases SCFA production

• Mediterranean diet adherence associated with reduced PD risk in case-control studies
• Higher MEDAS scores correlate with lower inflammatory markers
• Mediterranean diet improves cognitive function in elderly
• Pilot studies show benefits for GI symptoms in PD
• Meta-analyses support benefits for cardiovascular health

Ongoing Research

Multiple trials are investigating nutritional interventions in PD:

• Probiotic supplementation trials
• Prebiotic supplementation studies
• Calorie restriction and fasting protocols
• Ketogenic diet trials
• Polyphenol supplementation studies
• Vitamin D supplementation

Significance for Parkinson's Disease

Unmet Need

Current PD treatments:

• Levodopa/carbidopa: Symptomatic, does not modify disease progression
• Dopamine agonists: Symptomatic, with significant side effects
• MAO-B inhibitors: Symptomatic, mild disease-modifying potential
• Deep brain stimulation: Invasive, for advanced disease
• Physical therapy: Symptomatic support

Potential Impact

Success in this trial would represent:

Comparison with Other Approaches

| Intervention | Mechanism | Current Status | Advantages |
|--------------|-----------|---------------|-----------|
| Mediterranean diet | Multi-target (gut, inflammation) | Phase 2 | Safe, accessible |
| Probiotics | Gut modulation | Phase 2 | Targeted approach |
| Exercise | Neuroprotection | Standard of care | Proven benefits |
| Deep brain stimulation | Symptom control | Approved | Effective for motor |

External Links

• [ClinicalTrials.gov Record](https://clinicaltrials.gov/study/NCT07187739)
• [PubMed Search](https://pubmed.ncbi.nlm.nih.gov/?term=NCT07187739)

References