| Field | Value | |-------|-------| | NCT ID | NCT07001150 | | Status | Recruiting | | Phase | Phase 2 | | Sponsor | Tanta University | | Enrollment | 50 participants | | Start Date | March 15, 2024 | | Completion Date | March 2026 |
Study Design
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Silymarin for Neuroprotection and Symptom Management in Parkinson's Disease (NCT07001150)
Trial Overview
Mermaid diagram (expand to render)
| Field | Value | |-------|-------| | NCT ID | NCT07001150 | | Status | Recruiting | | Phase | Phase 2 | | Sponsor | Tanta University | | Enrollment | 50 participants | | Start Date | March 15, 2024 | | Completion Date | March 2026 |
Study Design
This single-arm Phase 2 trial evaluates the neuroprotective and symptomatic effects of silymarin (standardized milk thistle extract) in patients with Parkinson's Disease. Silymarin is a mixture of flavonolignans including silibinin, known for its potent antioxidant and anti-inflammatory properties.
Mechanism
Silymarin acts through multiple neuroprotective pathways:
Anti-inflammatory effects: Inhibits NF-κB signaling and reduces pro-inflammatory cytokine production
Mitochondrial protection: Helps maintain mitochondrial membrane potential and ATP production
Neurogenesis promotion: May support dopaminergic neuron survival and function
Inclusion Criteria
Age 40-75 years
Diagnosed with Parkinson's Disease (UK Brain Bank criteria)
Hoehn & Yahr stage 1-3
On stable PD medication for at least 4 weeks
MMSE score ≥ 24
Exclusion Criteria
Current use of silymarin or milk thistle supplements
Known allergy to Asteraceae plants
Severe liver disease
Coexisting neurological conditions
Outcome Measures
Primary Outcomes
Change in Unified Parkinson's Disease Rating Scale (UPDRS) Part I-III score
Change in plasma antioxidant capacity
Secondary Outcomes
Motor symptom fluctuations assessment
Non-motor symptom questionnaire scores
Quality of life measures (PDQ-39)
Clinical Significance
Silymarin represents a repurposed nutraceutical approach to neuroprotection in PD. If successful, this trial could establish a low-cost, widely-available neuroprotective strategy for PD patients.
Silymarin Pharmacology
Chemical Composition
Silymarin is a complex mixture of flavonolignans extracted from [silybum marianum](/entities/milk-thistle) (milk thistle), with silibinin (also called silymarin) being the most biologically active component[@silymarinmech]. The standardized extract typically contains:
Silibinin (70-80%): The major active component, consisting of two diastereomers, silybin A and silybin B
Isosilybin: Minor but biologically active flavonolignan
Silydianin and silychristine: Additional flavonolignans with antioxidant properties
Flavonoids: Taxifolin and other polyphenolic compounds
Pharmacokinetics
Absorption: Poor oral bioavailability due to extensive first-pass metabolism
Distribution: Crosses the blood-brain barrier to some extent
Metabolism: Hepatic metabolism via CYP450 enzymes
Excretion: Primarily biliary excretion
Preclinical Evidence in PD Models
Animal Studies
Multiple preclinical studies have demonstrated silymarin's neuroprotective effects in PD models[@pdneuroinflammation]:
6-OHDA model: Reduced dopaminergic neuron loss and improved behavioral outcomes
MPTP model: Protected against MPTP-induced parkinsonism
α-synuclein models: Reduced aggregation and protected neurons
Mechanistic Studies
The neuroprotective mechanisms include[@mitchondrial][@antioxidant]:
Upregulation of Nrf2 pathway and antioxidant enzymes
Inhibition of microglia activation and reduced pro-inflammatory cytokines
Preservation of mitochondrial complex I activity
Anti-apoptotic effects through modulation of Bcl-2 family proteins
[Silymarin: A comprehensive review of its pharmacology and therapeutic potential in neurological disorders (2023)](https://doi.org/10.1002/ptr.7891)
[Neuroinflammation in Parkinson's disease: mechanisms and therapeutic targets (2024)](https://doi.org/10.1186/s12974-024-03058-w)
[Mitochondrial dysfunction in Parkinson's disease: From pathogenesis to therapeutic targets (2023)](https://doi.org/10.1016/j.freeradbiomed.2023.02.012)
[Oxidative stress in neurodegenerative diseases: role of antioxidants (2024)](https://doi.org/10.3390/antiox13030345)
Pathway Diagram
The following diagram shows the key molecular relationships involving Silymarin for Neuroprotection and Symptom Management in Parkinson's Disease (NCT07001150) discovered through SciDEX knowledge graph analysis: