STARDYS
(2018)Objective
To assess efficacy and safety of bilateral GPi-DBS in medication-refractory tardive dystonia using a delayed-start, sham-controlled design
Study Summary
• Sham-controlled trial of pallidal DBS in 25 patients with tardive dystonia did NOT meet primary endpoint
• BFMDRS: active -22.8% vs sham -12.0% (P=0.48) - not significant
• Open-label extension at 6 months showed 41.5% improvement (P<0.01); trial underpowered (25 of 48 planned)
• BFMDRS: active -22.8% vs sham -12.0% (P=0.48) - not significant
• Open-label extension at 6 months showed 41.5% improvement (P<0.01); trial underpowered (25 of 48 planned)
Intervention
Bilateral GPi deep brain stimulation vs sham stimulation (delayed-start)
Inclusion Criteria
Age 18-75, tardive dystonia ≥18 months, marked disability despite medical treatment, stable psychiatric state, BFMDRS ≥8 or AIMS ≥16
Study Design
Arms: Active GPi-DBS vs Sham stimulation
Patients per Arm: DBS: 12; Sham: 13
Outcome
• Primary: Did NOT meet - BFMDRS difference 10.8% (P=0.48)
• Secondary: AIMS improved 29.6% vs -2.6% (P<0.01); 6-month open-label BFMDRS -41.5% (P<0.01)
• Secondary: AIMS improved 29.6% vs -2.6% (P<0.01); 6-month open-label BFMDRS -41.5% (P<0.01)
Bottom Line
Safinamide 100 mg/day significantly improved dyskinesia duration (DRT score) vs placebo as add-on to levodopa in mid-to-late PD: -1.08h/day vs -0.39h/day (P=0.003). Also reduced off-time. Published Movement Disorders. Phase 3.
Major Points
- Primary endpoint: change in DRT (dyskinesia rating time) — safinamide -1.08h vs placebo -0.39h (P=0.003).
- Off-time reduced: -1.2h vs -0.4h (P<0.01).
- Safinamide: dual mechanism — MAO-B inhibitor + sodium channel blocker (glutamate modulation).
- Dose: 100 mg/day as add-on to levodopa ± other PD medications.
- Phase 3, double-blind, placebo-controlled. 24-week treatment.
- AEs: dyskinesia (7% vs 3%), headache, nausea — generally well tolerated.
- Distinct from other MAO-B inhibitors: anti-glutamatergic property may specifically target dyskinesia.
- Supports safinamide for PD patients with bothersome dyskinesia on levodopa.
Study Design
- Study Type
- Randomized, double-blind, sham-controlled, delayed-start
- Blinding
- Double-blind
- Sample Size
- 25
- Follow-up
- 3 months blinded + 6 months open-label
- Centers
- 6
Primary Outcome
Definition: Percent change in BFMDRS at 3 months
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| 12.0% improvement (sham) | 22.8% improvement (active) | - | 0.48 (between-group) |
Limitations & Criticisms
- Underpowered (52% of planned enrollment)
- Baseline imbalance between groups
- Significant placebo effect in sham group
Citation
Brain Stimulation 2018;11(6):1368-1377