Study Rationale:
Our recent study (Xie et al., Neurology. 2015;84:415-420) found that 60Hz stimulation, compared to the traditional 130Hz, decreased aspiration frequency and swallowing difficulty, medication refractory freezing of gait (FOG), and other axial symptoms and parkinsonism in those with Parkinson's disease (PD) following bilateral subthalamic nuclei (brain regions associated with PD; STN) deep brain stimulation (DBS). The benefit of 60Hz stimulation persisted during the six-week study period, with worsening tremor in one participant. However, it remains unknown whether the benefit would persist through prolonged stimulation and whether there are carry-over effects across different conditions. Clarifying these questions is essential for the application of chronic 60Hz stimulation to treat medication-refractory axial symptoms.
Hypothesis:
The 60Hz stimulation, compared to 130Hz, should have a persistent benefit over an extended period (on average >eight-month study period) in reducing swallowing dysfunction, FOG and other axial symptoms in PD participants with bilateral STN DBS and medication -efractory FOG at 130Hz stimulation, corrected for potential carry-over effects between stimulation conditions.
Study Design:
We will enroll 14 PD participants with bilateral STN DBS and medication-refractory FOG at 130Hz for two visits at least six months apart. The six participants remaining on 60Hz stimulation after our previous study consisting of seven participants will be further assessed again at visit two at least 15 months after visit one. We will have 21 participants for visit one and at least 18 for visit two in this randomized, double-blind, prospective cross-over study with medication "on" in six to seven participants for each starting condition (60Hz vs 130Hz vs DBS "off"). Aspiration frequency and swallowing dysfunction, FOG and other axial and motor functions will be assessed under each DBS condition. Changes in measurements between 60Hz and 130Hz at each visit and under 60Hz between two visits will be analyzed, with swallowing function and FOG as primary outcomes and the rest as secondary outcomes, correcting for potential carry-over effects. Changes between other DBS conditions will also be explored in this two-year study.
Impact on Diagnosis/Treatment of Parkinson's Disease:
The chronic effect of 60Hz stimulation on dysphagia, FOG and other axial and motor symptoms in PD with bilateral STN DBS and medication-refractory FOG at 130Hz stimulation will have immediate impact on the treatment of difficult axial symptoms of high morbidity and mortality.
Next Steps for Development:
This trial, if successful, would have immediate clinical application to reduce dysphagia, FOG and other axial and motor symptoms in PD with bilateral STN DBS and medication-refractory FOG at 130Hz stimulation, which could potentially reduce morbidity and mortality.
Trial Phase: III