Pest-PD: Pesticides and Parkinson Disease (NCT06420310)
Overview
flowchart TD
PESTICIDES["PESTICIDES"] -->|"causes"| CARDIOVASCULAR_DISEASE["CARDIOVASCULAR_DISEASE"]
PESTICIDES["PESTICIDES"] -->|"causes"| BRAIN_AGING["BRAIN_AGING"]
Pesticides["Pesticides"] -->|"risk factor for"| Alzheimer_S_Disease["Alzheimer'S Disease"]
PESTICIDES["PESTICIDES"] -->|"causes"| Alzheimer_s_disease["Alzheimer's disease"]
Pesticides["Pesticides"] -->|"causes"| Neuronal_Dysfunction["Neuronal Dysfunction"]
pesticides["pesticides"] -->|"causes"| Parkinson_s_disease["Parkinson's disease"]
pesticides["pesticides"] -->|"causes"| alpha_synuclein["alpha-synuclein"]
style pesticides fill:#4fc3f7,stroke:#333,color:#000
The Pest-PD study (NCT06420310) is a case-control cross-sectional prevalence study conducted by [Hospital Universitario de Burgos](https://clinicaltrials.gov/study/NCT06420310) in Spain. The study aims to determine whether individuals exposed to pesticides have a higher prevalence of preclinical and prodromal Parkinson's disease compared to unexposed controls. This is an epidemiological study investigating the environmental etiology of [Parkinson's disease](/diseases/parkinson-disease) through the lens of pesticide exposure as a major modifiable risk factor.
...Pest-PD: Pesticides and Parkinson Disease (NCT06420310)
Overview
Mermaid diagram (expand to render)
The Pest-PD study (NCT06420310) is a case-control cross-sectional prevalence study conducted by [Hospital Universitario de Burgos](https://clinicaltrials.gov/study/NCT06420310) in Spain. The study aims to determine whether individuals exposed to pesticides have a higher prevalence of preclinical and prodromal Parkinson's disease compared to unexposed controls. This is an epidemiological study investigating the environmental etiology of [Parkinson's disease](/diseases/parkinson-disease) through the lens of pesticide exposure as a major modifiable risk factor.
Unlike interventional clinical trials, Pest-PD is an observational study that will assess biomarker and clinical sign prevalence in pesticide-exposed vs. unexposed populations. The mechanistic focus aligns with the broader literature implicating pesticide exposure as a dominant environmental driver of [Parkinson's disease risk](/mechanisms/environmental-toxins-parkinson-risk)[@tang2024][@ball2019].
Trial Details
| Attribute | Value |
|-----------|-------|
| NCT Number | NCT06420310 |
| Acronym | Pest-PD |
| Official Title | Prevalence of Preclinical and Prodromal Parkinson Disease in Subjects Exposed to Pesticides |
| Study Type | Observational (Case-Control) |
| Overall Status | Recruiting |
| Study Start Date | April 2024 |
| Estimated Primary Completion | September 2028 |
| Estimated Study Completion | December 2028 |
| Target Duration | 3 Years |
| Enrollment | 260 (estimated) |
| Condition | Pesticide-Induced Parkinsonism |
| Biospecimens | Blood samples with DNA |
| Data Sharing | No IPD sharing |
Scientific Rationale
Pesticides and Neurodegeneration
Epidemiological evidence has consistently demonstrated that pesticide exposure significantly increases [Parkinson's disease](/diseases/parkinson-disease) risk. Key mechanistic pathways include:
MPTP-like compounds: The landmark 1983 Langston study established that compounds structurally similar to meperidine (MPTP) can induce parkinsonism in humans, directly linking pesticide-like molecules to dopaminergic neurodegeneration.
Rotenone and paraquat: Chronic systemic exposure to [rotenone](/mechanisms/environmental-toxins-parkinson-risk) and [paraquat](/mechanisms/environmental-toxins-parkinson-risk) in animal models reproduces the full spectrum of [Parkinson's disease](/diseases/parkinson-disease) features, including mitochondrial complex I dysfunction, alpha-synuclein aggregation, and selective dopaminergic neuron loss[@betarbet2000].
Epigenetic mechanisms: Pesticides modify the expression of genes related to [Parkinson's disease](/diseases/parkinson-disease) through epigenetic mechanisms, particularly affecting mitochondrial function and protein quality control pathways[@ascher2021].
Gene-environment interaction: [Genetic modifiers](/diseases/parkinson-disease) of [Parkinson's disease](/diseases/parkinson-disease) risk significantly influence individual susceptibility to pesticide-induced neurodegeneration[@hernandez2023].Prodromal PD Assessment
The study focuses on detecting [prodromal Parkinson's disease](/diseases/parkinson-disease) — the pre-diagnostic phase characterized by non-motor symptoms that precede motor diagnosis by years to decades. Key prodromal markers include:
- Olfactory dysfunction: Hyposmia is one of the earliest and most prevalent prodromal signs
- REM sleep behavior disorder (RBD): Strongly predictive of synucleinopathies
- Constipation and GI dysfunction: Reflects early alpha-synuclein pathology in the enteric nervous system
- Depression and anxiety: May precede motor symptoms
- Subtle motor signs: Bradykinesia, gait changes, micrographia (pre-motor PD)
Study Design
Structure
Pest-PD Study Design
├── Cases: Farmers with occupational pesticide exposure
│ └── N ≈ 130 individuals
└── Controls: Un-exposed individuals
└── N ≈ 130 individuals
- Observational Model: Case-Control
- Time Perspective: Cross-sectional
- Sampling Method: Non-probability sample
- Target Population: Subjects not diagnosed with PD living in the Burgos region, Spain
Key Elements
Pesticide exposure determination: Standardized questionnaires to quantify occupational pesticide exposure history
Preclinical PD detection: Biological biomarkers of neurodegeneration
Prodromal PD sign assessment: Standardized clinical assessments of early non-motor symptoms
Multivariate analysis: Statistical adjustment for clinical covariates including age, gender, and other risk factorsEligibility Criteria
Inclusion Criteria
- Cases: Farmers with occupational exposure to pesticides
- Controls: Individuals with no occupational pesticide exposure
- Age range: 45–55 years
- Healthy volunteers: Yes
Exclusion Criteria
- Subjects without signed informed consent form
- Subjects with significant neurological conditions (other than prodromal signs)
- Prior diagnosis of [Parkinson's disease](/diseases/parkinson-disease) or parkinsonism
Biological Sample Collection
The study collects blood samples from both cases and controls, including DNA for genomic analysis. This biospecimen collection enables:
- Genetic analysis: Examining gene-environment interactions, including [GBA](/diseases/gba-related-parkinsonism), [LRRK2](/genes/lrrk2), [SNCA](/genes/snca), and other [Parkinson's disease](/diseases/parkinson-disease) risk genes
- Biomarker studies: Neurofilament light chain (NfL), alpha-synuclein in blood/serum, and other neurodegenerative markers
- Epigenetic profiling: DNA methylation studies to assess pesticide-induced epigenetic modifications
Outcome Measures
Primary Outcome
| Measure | Description | Time Frame |
|---------|-------------|------------|
| Prodromal PD prevalence | Presence of early non-motor symptoms associated with preclinical/prodromal [Parkinson's disease](/diseases/parkinson-disease) | Over the last year |
Study Endpoints
The study will compare:
- Prevalence of prodromal PD signs in pesticide-exposed vs. unexposed groups, stratified by age and gender
- Biological biomarker profiles in exposed vs. unexposed cohorts
- Risk of presenting early [Parkinson's disease](/diseases/parkinson-disease) after adjustment for clinical covariates
Location
| Facility | City | Country | Status |
|----------|------|---------|--------|
| Hospital Universitario de Burgos | Burgos | Spain | Recruiting |
Principal Investigator
Esther Cubo, MD, PhD
Hospital Universitario de Burgos
Contact: +34 947 256 533 | mcubo@saludcastillayleon.es
Significance for NeuroWiki
Mechanistic Context
The Pest-PD study directly supports the environmental etiology section of [Environmental Toxins and Parkinson's Disease Risk](/mechanisms/environmental-toxins-parkinson-risk). Key mechanistic connections:
- Pesticide → mitochondrial dysfunction → alpha-synuclein aggregation → dopaminergic neuron loss: This pathway chain is well-established in the literature[@betarbet2000][@tang2024]
- Epigenetic modifications: Pesticide exposure changes gene expression related to [Parkinson's disease](/diseases/parkinson-disease) without changing DNA sequence
- Gene-environment interactions: Individual genetic susceptibility (e.g., [GBA](/diseases/gba-related-parkinsonism), [SNCA](/genes/snca) multiplications) modulates pesticide toxicity
Cross-Linking Opportunities
This trial page provides anchor points for:
- [Environmental risk factors mechanism page](/mechanisms/environmental-risk-factors)
- [Parkinson's disease etiology section](/diseases/parkinson-disease)
- [Occupational health and neurodegeneration](/mechanisms/environmental-toxins-parkinson-risk)
- [Prodromal Parkinson's disease biomarkers](/mechanisms/prodromal-parkinson-markers) (if such a page exists)
Broader Research Context
The Pest-PD study complements several other research streams in the NeuroWiki knowledge base:
Genetic studies: [GBA](/diseases/gba-related-parkinsonism) and [LRRK2](/genes/lrrk2) mutations that interact with environmental exposures
Mitochondrial pathways: Complex I deficiency and pesticide-induced mitochondrial dysfunction
Alpha-synuclein biology: How pesticides may trigger misfolding and aggregation
Neuroinflammation: Pesticide-induced microglial activationResearch Team
Hospital Universitario de Burgos serves as the lead sponsor and coordinating center. The study represents a collaborative effort between neurology, epidemiology, and occupational medicine specialists in Spain.