Parkinson Disease
Conditions
Brief summary
This trial aims to understand the mechanism and to test whether transcranial direct current stimulation (tDCS) combined with transcranial ultrasound (TUS) (tDCS+TUS) combined with physical therapy (PT) will induce significant therapeutic effects in postural instability in Parkinson's disease (PT) patients. The investigators designed a double-blinded, placebo controlled, randomized study to investigate the effects of 2 weeks of TDCS+TUS on postural instability in PD patients receiving PT. (Followed by biweekly sessions for 2 more weeks in Phase II)
Detailed description
Current treatments for Parkinson's Disease (PD), including pharmacological (levodopa) and surgical (DBS) methods, have limited impact on postural instability. Physical therapy (PT) for PD is becoming increasingly used as a means to induce benefits on patient balance. However, limits in efficacy and consistency still exist. In this study, the investigators will test the effects of TDCS+TUS combined with PT on postural instability of PD patients.
Interventions
DEVICEActive Comparator: Active tDCS and Active TUS
Device: Transcranial Direct Current Stimulation (tDCS) Subjects will receive 20 minutes of either active or sham tDCS at intensity of 2mA. The anodal electrode will be placed over the primary motor cortex contralateral to the most painful side, and the cathodal electrode will be placed over the contralateral supraorbital area. In the sham group, the tDCS device will not be active for the full 20 minutes. Device: Transcranial Ultrasound (TUS) Subjects will receive 20 minutes of either active or sham TUS. During active stimulation the ultrasound will be active for the full 20 minutes- however, during sham stimulation the ultrasound will not be active for the full 20 minutes.
DEVICESham Comparator: Sham TDCS and Sham TUS
Device: SHAM Comparator Device: transcranial Direct Current Stimulation (tDCS) Subjects will receive 20 minutes of either active or sham tDCS at intensity of 2mA. The anodal electrode will be placed over the primary motor cortex contralateral to the most painful side, and the cathodal electrode will be placed over the contralateral supraorbital area. In the sham group, the tDCS device will not be active for the full 20 minutes. Device: Transcranial Ultrasound (TUS) Subjects will receive 20 minutes of either active or sham TUS. During active stimulation the ultrasound will be active for the full 20 minutes- however, during sham stimulation the ultrasound will not be active for the full 20 minutes.
OTHERPhysical Therapy
All subjects will enroll in a conventional PT balance and gait focused training program, and will receive PT 3x/week over the two weeks of stimulation for 45 minutes following the stimulation sessions when applicable. (And during the biweekly sessions for Phase II)
Sponsors
Spaulding Rehabilitation Hospital
Highland Instruments, Inc.
National Institute of Neurological Disorders and Stroke (NINDS)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
1. Diagnosis of "probable" or "possible" PD, as defined by the current clinical criteria (Gelb D, Oliver E, Gilman S. Diagnostic Criteria for Parkinson's Disease. Arch Neurol.1999;56:33-39) as confirmed by co-investigator neurologist, or confirmation via medical records or a letter from patient physician; 2. Complaints about balance impairment or postural instability due to PD (self-report); 3. Age from 40 to 90 years old; 4. Taking stable medications for PD for at least 30 days.
Exclusion criteria
1. Features suggestive of other causes of parkinsonism/Parkinson's-plus syndromes; 2. History of deep brain stimulation or brain ablation surgeries, malignant mass brain lesions; 3. History of schizophrenia, bipolar illness; history of alcohol/drug abuse within the past 6 months; 4. Need for rapid clinical response due to conditions such as initiation, psychosis, or suicidality; 5. Contraindications to transcranial brain stimulation or TUS, i.e. metal in the head, implanted brain medical devices, etc.; 6. Unstable medical conditions (e.g., uncontrolled diabetes, uncompensated cardiac issues, heart failure, uncompensated pulmonary disease, or chronic obstructive pulmonary disease); 7. Pregnancy. 8. Epilepsy or disorders that significantly increase likelihood of seizures including: severe traumatic brain injury, congenital birth defects leading to seizures, brain tumor, metabolic disorders associated with seizures, intracranial or subarachnoid hemorrhage, and nonlacunar strokes. 9. Recent (\<= 2 months) or planned enrollment in an additional physician prescribed physical therapy program during their time in the trial. 10. Presence of another disorder that might have a significant impact on balance (as assessed by a co-investigator neurologist). 11. Bed or wheelchair-bound
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Improvement in Unified Parkinson's Disease Rating Scale (UPDRS) Part III | Change from baseline to Day 14 (end of stimulation treatment). | Motor function was assessed using the Unified Parkinson's Disease Rating Scale (UPDRS) Part III - Motor Examination, which measures tremor, rigidity, bradykinesia, postural instability, and gait. Scores range from 0 to 108, where higher scores indicate worse motor impairment (i.e., lower scores represent better motor function). |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORFelipe Fregni, MD, PhD
Spaulding Rehabilitation Hospital
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Active tDCS and Active TUS Active tDCS and Active TUS for 20 min
Active Comparator: Active tDCS and Active TUS: Device: Transcranial Direct Current Stimulation (tDCS) Subjects will receive 20 minutes of either active or sham tDCS at intensity of 2mA. The anodal electrode will be placed over the primary motor cortex contralateral to the most painful side, and the cathodal electrode will be placed over the contralateral supraorbital area. In the sham group, the tDCS device will not be active for the full 20 minutes.
Device: Transcranial Ultrasound (TUS) Subjects will receive 20 minutes of either active or sham TUS. During active stimulation the ultrasound will be active for the full 20 minutes- however, during sham stimulation the ultrasound will not be active for the full 20 minutes.
Physical Therapy: All subjects will enroll in a conventional PT balance and gait focused training program, and will receive PT 3x/week over the two weeks of stimulation for 45 minutes following the stimulation sessions when applicable. (And during the biweekly sessions for Phase II) | 20 |
| Sham TDCS and Sham TUS Sham TDCS and Sham TUS for 20 min
Sham Comparator: Sham TDCS and Sham TUS: Device: SHAM Comparator Device: transcranial Direct Current Stimulation (tDCS) Subjects will receive 20 minutes of either active or sham tDCS at intensity of 2mA. The anodal electrode will be placed over the primary motor cortex contralateral to the most painful side, and the cathodal electrode will be placed over the contralateral supraorbital area. In the sham group, the tDCS device will not be active for the full 20 minutes.
Device: Transcranial Ultrasound (TUS) Subjects will receive 20 minutes of either active or sham TUS. During active stimulation the ultrasound will be active for the full 20 minutes- however, during sham stimulation the ultrasound will not be active for the full 20 minutes.
Physical Therapy: All subjects will enroll in a conventional PT balance and gait focused training program, and will receive PT 3x/week over the two weeks of stimulation for 45 minutes following the stimulation sessions when applicable. (And during the biweekly sessions for Phase II) | 20 |
| Total | 40 |
Baseline characteristics
| Characteristic | Active tDCS and Active TUS | Sham TDCS and Sham TUS | Total |
|---|---|---|---|
| Age, Continuous | 65.35 years STANDARD_DEVIATION 9.33 | 68.2 years STANDARD_DEVIATION 9.13 | 66.77 years STANDARD_DEVIATION 9.23 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 0 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 18 Participants | 20 Participants | 38 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment United States | 20 participants | 20 participants | 40 participants |
| Sex: Female, Male Female | 7 Participants | 4 Participants | 11 Participants |
| Sex: Female, Male Male | 13 Participants | 16 Participants | 29 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 20 |
| other Total, other adverse events | 20 / 20 | 13 / 20 |
| serious Total, serious adverse events | 0 / 20 | 0 / 20 |
Outcome results
Primary
Improvement in Unified Parkinson's Disease Rating Scale (UPDRS) Part III
Motor function was assessed using the Unified Parkinson's Disease Rating Scale (UPDRS) Part III - Motor Examination, which measures tremor, rigidity, bradykinesia, postural instability, and gait. Scores range from 0 to 108, where higher scores indicate worse motor impairment (i.e., lower scores represent better motor function).
Time frame: Change from baseline to Day 14 (end of stimulation treatment).
Population: Intention-to-treat population: all randomized participants with Parkinson's disease
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active tDCS and Active TUS | Improvement in Unified Parkinson's Disease Rating Scale (UPDRS) Part III | 4.42 Scores on a scale (UPDRS). | Standard Error 0.42 |
| Sham TDCS and Sham TUS | Improvement in Unified Parkinson's Disease Rating Scale (UPDRS) Part III | 0.12 Scores on a scale (UPDRS). | Standard Error 0.43 |