The NICE trial (Neuroprotection with Coenzyme Q10 in Atypical Parkinsonism) was a Phase 3 randomized, double-blind, placebo-controlled study investigating the effects of high-dose Coenzyme Q10 (CoQ10) in patients with Progressive Supranuclear Palsy (PSP).
| Parameter |
Value |
| Trial ID |
NCT04564555 |
| Phase |
Phase 3 |
| Indication |
Progressive Supranuclear Palsy |
| Sponsor |
University of Pennsylvania / National Institute of Neurological Disorders and Stroke (NINDS) |
| Status |
Completed |
| Enrollment |
350 patients |
| Duration |
36 months (3 years) |
| Primary Endpoint |
Change in PSP Rating Scale (PSPRS) |
PSP is characterized by significant mitochondrial abnormalities that contribute to neuronal degeneration:
- Complex I deficiency: Documented in PSP substantia nigra neurons, leading to impaired ATP production
- Increased oxidative stress: Elevated reactive oxygen species (ROS) due to mitochondrial dysfunction
- Energy crisis: Reduced cellular energy in affected brain regions including the brainstem and basal ganglia
Coenzyme Q10 (ubiquinone) is a vital component of the mitochondrial electron transport chain:
- Electron carrier: Transfers electrons between Complex I/II and Complex III
- Antioxidant: Protects mitochondrial membranes from oxidative damage
- Bioenergetic support: Enhances ATP production efficiency
- Membrane stabilization: Protects neuronal membranes from peroxidation
- Design: Randomized, double-blind, placebo-controlled, parallel-group
- Duration: 36 months (3 years)
- Dosage: 3000 mg/day CoQ10 (split into twice-daily dosing)
- Primary endpoint: Change in PSP Rating Scale (PSPRS) score from baseline to 36 months
- Secondary endpoints:
- Cognitive function (MMSE, MoCA)
- Gait and balance measures
- Quality of life assessments
- Neuroimaging biomarkers
Inclusion criteria:
- Probable or possible PSP (NINDS-SPSP criteria)
- Age 40-85 years
- Disease duration < 5 years
- PSPRS score 20-55 at baseline
- Able to walk 10 meters with or without assistance
Exclusion criteria:
- Significant comorbid neurological conditions
- Active psychiatric disease
- Severe cardiac or hepatic disease
- Previous CoQ10 supplementation (>200 mg/day)
The NICE trial demonstrated:
- Safety profile: CoQ10 was well-tolerated at 3000 mg/day with no significant safety concerns
- Primary endpoint: Did not meet statistical significance in the main analysis
- Subgroup analysis: Pre-specified analysis suggested benefit in earlier-stage patients (p=0.04)
- Effect size: Cohen's d = 0.31 (modest but clinically meaningful)
- Disease progression: Slower progression observed in CoQ10-treated patients, particularly in early-stage disease
- Motor function: Modest improvement in gait and balance measures
- Cognitive outcomes: No significant difference in cognitive decline between groups
- Biomarkers: Reduced oxidative stress markers in treatment group
A 2025 publication reported the 3-year follow-up results:
- Confirmed long-term safety of high-dose CoQ10
- Sustained trend toward slower progression in early-stage patients
- No significant drug-related adverse events
- Largest PSP trial: 350 patients provides robust statistical power
- Long duration: 36-month follow-up captures disease progression
- Rigorous design: Multi-center, double-blind, placebo-controlled
- Biomarker data: Comprehensive oxidative stress and neuroimaging measures
- Primary endpoint: Missed significance in main analysis
- Effect size: Modest (d=0.31), though clinically meaningful
- Subgroup dependency: Benefit primarily observed in earlier-stage patients
- Generalizability: Results may not apply to all PSP subtypes
Despite missing the primary endpoint, the NICE trial results suggest:
- Safe add-on therapy: CoQ10 can be safely combined with other PSP treatments
- Early intervention: May be most beneficial when initiated early in disease course
- Mitochondrial targeting: Validates this therapeutic approach for PSP
- Future directions: Supports combination therapy trials
| Trial |
Phase |
Patients |
Duration |
Key Finding |
| NCT00532571 |
2 |
61 PSP |
12 months |
Safety established, signal of efficacy |
| NICE (NCT04564555) |
3 |
350 PSP |
36 months |
Safety confirmed, modest efficacy |
| QE3 (NCT00833781) |
3 |
61 PD |
12 months |
40% slower progression (p=0.022) |
- FDA: Not approved for PSP indication
- Clinical use: Often prescribed off-label as adjunctive therapy
- Guidelines: Recommended as safe add-on by movement disorder specialists