German PD Study Group DBS Trial
(2006)Objective
To compare deep-brain stimulation of the subthalamic nucleus plus medication versus best medical management alone in patients with advanced Parkinson's disease and severe motor complications.
Study Summary
• Motor function (UPDRS-III off medication) improved 41% with DBS vs no change with medication (P<0.001)
• Serious adverse events more common with DBS (13% vs 4%, P=0.04) including 1 fatal intracerebral hemorrhage
Intervention
Bilateral STN deep-brain stimulation within 6 weeks of enrollment vs best medical treatment for 6 months
Inclusion Criteria
Adults <75 years with idiopathic PD for >=5 years, parkinsonian motor symptoms or dyskinesias limiting ADLs despite optimal medical therapy, no dementia or major psychiatric illness
Study Design
Arms: Neurostimulation (STN DBS), Best Medical Treatment
Patients per Arm: Neurostimulation: 78, Medical Treatment: 78
Outcome
• Immobility reduced by 4.2 hrs/day; mobility without dyskinesia increased by 4.4 hrs/day
• Levodopa equivalent reduced 50% in DBS group vs 8% in medical group
Bottom Line
In patients under 75 years with advanced Parkinson's disease, bilateral STN neurostimulation was more effective than medical management alone, resulting in 25% improvement in quality of life (PDQ-39) and 41% improvement in motor symptoms without medication (UPDRS-III), though serious adverse events were more common (13% vs 4%).
Major Points
- Randomized, controlled, unblinded trial comparing bilateral STN-DBS plus medical management versus medical management alone
- 156 patients (78 matched pairs) at 10 academic centers in Germany and Austria
- Patients had disease duration ≥5 years, were <75 years old, and had motor symptoms limiting daily activities despite optimal medical therapy
- Primary endpoints: changes in PDQ-39 summary index and UPDRS-III scores without medication from baseline to 6 months
- Neurostimulation resulted in 25% improvement in PDQ-39 (41.8 to 31.8) vs no change with medication alone (32.6 to 34.0), P<0.001
- UPDRS-III without medication improved 41% with neurostimulation (48.0 to 28.3) vs no change with medication, P<0.001
- Patient diaries: reduced immobility time by 4.2 hours, increased mobility without dyskinesias by 4.4 hours
- Dopaminergic medication reduced by 50% in DBS group vs 8% in medical group
- Three deaths in neurostimulation group: intracerebral hematoma, pneumonia, suicide
Study Design
- Study Type
- Randomized controlled trial
- Randomization
- Yes
- Blinding
- Unblinded
- Sample Size
- 156
- Follow-up
- 6 months
- Centers
- 10
- Countries
- Germany, Austria
Primary Outcome
Definition: PDQ-39 summary index (quality of life, 0-100, higher = worse)
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| Baseline 32.6±16.0, 6 months 34.0±14.4 (no change) | Baseline 41.8±13.9, 6 months 31.8±16.0 (25% improvement) | - | <0.001 |
Limitations & Criticisms
- Unblinded trial design - no sham surgery control
- Possible placebo effect from surgery not controlled
- Short 6-month follow-up duration
- Higher serious adverse event rate in DBS group including 3 deaths
- Baseline PDQ-39 scores differed between groups despite randomization
- Results may not generalize to patients over 75 years
Citation
N Engl J Med 2006;355:896-908