Clinical trial NCT02549859: Long-term Effect of Low Frequency Stimulation on Aspiration and Freezing of Gait in PD With STN DBS
Official title: Long-term Effect of Low Frequency 60Hz Stimulation on Aspiration, Freezing of Gait and Other Axial and Motor Symptoms in PD Patients With Bilateral STN DBS
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Parkinson's Disease
Keywords: DBS
Low frequency stimulation
Dysphagia
Freezing of gait
Lead sponsor: University of Chicago
Sponsor class: OTHER
Collaborators: name: Michael J. Fox Foundation for Parkinson's Research
First posted: 2015-09-15
Enrollment: 11
Sex: ALL
Minimum age (years): 45
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Our recent study (Xie et al, Neurology 2015; 84: 415-420) found that bilateral STN DBS of 60Hz, compared to the traditional 130Hz, decreased the aspiration frequency and swallowing difficulty, freezing of gait (FOG), and other axial symptoms and parkinsonism in Parkinson patients with FOG refractory to 130Hz and medications. The benefit of 60Hz stimulation persisted during the 6-week study period, but with worsening tremor in one patient. However, it remains unknown whether the benefit of 60Hz would persist on prolonged stimulation period, and whether there is carry-over effect across different conditions. Hence, the investigators would like to test the hypothesis that the 60Hz stimulation, compared to 130Hz might have persistent benefit over an extended period in reducing the swallowing dysfunction, FOG, and other axial symptoms in these PD patients even after correcting the potential carry-over effect.

Detailed description: The investigators will enroll 14 Parkinson patients with bilateral STN DBS and refractory FOG to 130Hz stimulation and dopaminergic medications for two visits of at least 6-month apart. The 6 patients remaining on 60Hz stimulation after our previous study consisting of 7 patients will be assessed once again as visit-2 after previous visit-1 of their last study. We anticipate to have 20 patents complete for visit-1 and at least 18 patients complete for visit-2 in this randomized double-blind prospective crossover study with their usual medication "on" state, with 6-7 patients on each starting condition (60Hz vs 130Hz vs DBS off). Swallowing function on modified barium swallowing test and swallowing questionnaire, FOG in stand-walk-sit test and questionnaire, and other axial and motor function on UPDRS-III 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, and the rest as secondary outcomes, correcting for potential carryover effect. Changes between other DBS conditions might also be explored in this 2-year study.

This would be the first study on the long-term effect of 60Hz stimulation on dysphagia, FOG and other axial and motor symptoms in Parkinson patients with bilateral STN DBS and FOG refractory to 130Hz stimulation and dopaminergic medications, which will have significant impact on the treatment of difficult axial symptoms of high morbidity and mortality.

Eligibility criteria: Inclusion Criteria:

* PD patients with bilateral STN DBS placement and FOG at 130Hz even at usual medication "on" state.

Exclusion Criteria:

* Known history of recent aspiration pneumonia

Primary outcomes:
measure: Frequency of Aspiration Events on Videofluoroscopic Swallow Study at Visit 1
timeFrame: Immediately following treatment for at least 30 minutes
measure: Perceived Swallowing Difficulty on Swallowing Disturbance Questionnaire at Visit 1
timeFrame: Immediately following treatment for at least 30 minutes
measure: Freezing of Gait Questionnaire at Visit 1
timeFrame: Immediately following treatment for at least 30 minutes
measure: Stand-Walk-Sit Freezing of Gait Spells at Visit 1
timeFrame: Immediately following treatment for at least 30 minutes
measure: Stand-Walk-Sit Time at Visit 1
timeFrame: Immediately following treatment for at least 30 minutes
measure: Frequency of Aspiration Events on Videofluoroscopic Swallow Study at Visit 2
timeFrame: Immediately following treatment for at least 30 minutes
measure: Perceived Swallowing Difficulty on Swallowing Disturbance Questionnaire at Visit 2
timeFrame: Immediately following treatment for at least 30 minutes
measure: Freezing of Gait Questionnaire at Visit 2
timeFrame: Immediately following treatment for at least 30 minutes
measure: Stand-Walk-Sit Freezing of Gait Spells at Visit 2
timeFrame: Immediately following treatment for at least 30 minutes
measure: Stand-Walk-Sit Time at Visit 2
timeFrame: Immediately following treatment for at least 30 minutes
Secondary outcomes:
measure: Unified Parkinson's Disease Rating Scale-III Total Score at Visit 1
timeFrame: Immediately following treatment for at least 30 minutes
measure: Axial Subscore of Unified Parkinson's Disease Rating Scale-III at Visit 1
timeFrame: Immediately following treatment for at least 30 minutes
measure: Bradykinesia Subscore of Unified Parkinson's Disease Rating Scale-III at Visit 1
timeFrame: Immediately following treatment for at least 30 minutes
measure: Rigidity Subscore of Unified Parkinson's Disease Rating Scale-III at Visit 1
timeFrame: Immediately following treatment for at least 30 minutes
measure: Tremor Subscore of Unified Parkinson's Disease Rating Scale-III at Visit 1
timeFrame: Immediately following treatment for at least 30 minutes
measure: Unified Parkinson's Disease Rating Scale-III Total Score at Visit 2
timeFrame: Immediately following treatment for at least 30 minutes
measure: Axial Subscore of Unified Parkinson's Disease Rating Scale-III at Visit 2
timeFrame: Immediately following treatment for at least 30 minutes
measure: Bradykinesia Subscore of Unified Parkinson's Disease Rating Scale-III at Visit 2
timeFrame: Immediately following treatment for at least 30 minutes
measure: Rigidity Subscore of Unified Parkinson's Disease Rating Scale-III at Visit 2
timeFrame: Immediately following treatment for at least 30 minutes
measure: Tremor Subscore of Unified Parkinson's Disease Rating Scale-III at Visit 2
timeFrame: Immediately following treatment for at least 30 minutes
Other outcomes:
Locations:
city: Chicago
country: United States
facility: University of Chicago, Department of Neurology
state: Illinois
Study officials:
affiliation: Department of Neurology, University of Chicago
name: Tao Xie, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Xie T, Vigil J, MacCracken E, Gasparaitis A, Young J, Kang W, Bernard J, Warnke P, Kang UJ. Low-frequency stimulation of STN-DBS reduces aspiration and freezing of gait in patients with PD. Neurology. 2015 Jan 27;84(4):415-20. doi: 10.1212/WNL.0000000000001184. Epub 2014 Dec 24.
citation: Xie T, Bloom L, Padmanaban M, Bertacchi B, Kang W, MacCracken E, Dachman A, Vigil J, Satzer D, Zadikoff C, Markopoulou K, Warnke P, Kang UJ. Long-term effect of low frequency stimulation of STN on dysphagia, freezing of gait and other motor symptoms in PD. J Neurol Neurosurg Psychiatry. 2018 Sep;89(9):989-994. doi: 10.1136/jnnp-2018-318060. Epub 2018 Apr 13.