Parkinson's Disease: Enhancing Physical Therapy With Brain Stimulation for Treating Postural Instability.

• ClinicalTrials.gov Identifier: NCT03981055
• Recruitment Status: Recruiting
• First Posted: June 10, 2019
• Last Update Posted: August 16, 2022
• Sponsor: Spaulding Rehabilitation Hospital
• Collaborator: Highland Instruments, Inc.
• Information provided by (Responsible Party): Felipe Fregni, MD, PhD, MPH, Spaulding Rehabilitation Hospital

Study Description

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)

Condition or disease	Intervention/treatment	Phase
Parkinson Disease	Device: Active Comparator: Active tDCS and Active TUS; Device: Sham Comparator: Sham TDCS and Sham TUS; Other: Physical Therapy	Not Applicable

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 40 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Other
• Official Title: Parkinson's Disease: Enhancing Physical Therapy With Brain Stimulation for Treating Postural Instability.
• Actual Study Start Date: January 23, 2020
• Estimated Primary Completion Date: August 1, 2023
• Estimated Study Completion Date: August 30, 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: Active tDCS and Active TUS; Active tDCS and Active TUS for 20 min	Device: 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.; Other: 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)
Sham Comparator: Sham TDCS and Sham TUS; Sham TDCS and Sham TUS for 20 min	Device: 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.; Other: 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)

Outcome Measures

Primary Outcome Measures :

1. Change in postural sway [ Time Frame: 1 week pre intervention, immediately before intervention, following stimulation treatment (stimulation day 5, 10 and 14), and all follow ups ]
   Postural sway will be assessed through biomechanical assessments using a set of integrated sensors including accelerometers, gyroscopes, force sensors, and motion-capture cameras.

Secondary Outcome Measures :

1. Unified Parkinson's Disease Rating Scale (UPDRS) [ Time Frame: 1 week pre intervention, immediately before intervention, following stimulation treatment (stimulation day 5, 10 and 14), and all follow ups ]
   Motor function (including tremor, bradykinesia, postural instability and gait), non-motor symptoms, activities of daily living and complications of therapy will be investigated per UPDRS (parts I-IV); staging of PD and ability to perform activities of daily living will also be investigated via UPDRS parts V and VI. We already have experience using this assessment in several previous brain stimulation PD studies.
2. Leg Agility [ Time Frame: 1 week pre intervention, immediately before intervention, following stimulation treatment (stimulation day 5, 10 and 14), and all follow ups ]
   kinematic changes will be assessed with kinematic metrics (e.g., speed (m/s)) taken with a biomechanical assessment suite throughout the study.
3. Arising from a chair [ Time Frame: 1 week pre intervention, immediately before intervention, following stimulation treatment (stimulation day 5, 10 and 14), and all follow ups ]
   kinematic changes will be assessed with kinematic metrics (e.g., time to complete task) taken with a biomechanical assessment suite throughout the study.
4. Balance [ Time Frame: 1 week pre intervention, immediately before intervention, following stimulation treatment (stimulation day 5, 10 and 14), and all follow ups ]
   kinematic changes will be assessed with kinematic metrics taken during a modified Romberg exam (e.g., change in center of pressure over a fixed time interval (cm)) with a biomechanical assessment suite throughout the study.
5. Gait [ Time Frame: 1 week pre intervention, immediately before intervention, following stimulation treatment (stimulation day 5, 10 and 14), and all follow ups ]
   changes in the walking speed, gait asymmetry, stride length, walking smoothness, and gait freezing kinematic characteristics (e.g., m/s) will be assessed with a biomechanical assessment suite throughout the study
6. Toe tapping [ Time Frame: 1 week pre intervention, immediately before intervention, following stimulation treatment (stimulation day 5, 10 and 14), and all follow ups ]
   kinematic changes will be assessed with kinematic metrics (e.g., speed (m/s)) taken with a biomechanical assessment suite throughout the study.

Eligibility Criteria

• Ages Eligible for Study: 40 Years to 90 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Contacts

Contact: Felipe Fregni, MD, PhD; 6179526158; Fregni.Felipe@mgh.harvard.edu

Contact: Elly Pichardo, MD; 617-952-6154; epichardo@partners.org

Locations

United States, Massachusetts

Spaulding Rehabilitation Network Research Institute; Recruiting

Charlestown, Massachusetts, United States, 02129

Contact: Felipe Fregni, MD PhD MPH 617-952-6156 ffregni@partners.org

Contact: Elly Pichardo, MD 617-952-6154 epichardo@partners.org

Principal Investigator: Felipe Fregni, MD PhD MPH

Sponsors and Collaborators

Spaulding Rehabilitation Hospital

Highland Instruments, Inc.

Investigators

• Principal Investigator: Felipe Fregni, MD, PhD; Spaulding Rehabilitation Hospital

More Information

• Responsible Party: Felipe Fregni, MD, PhD, MPH, Director, Spaulding Neuromodulation Center, Spaulding Rehabilitation Hospital & Massachusetts General Hospital, Harvard Medical School, Spaulding Rehabilitation Hospital
• ClinicalTrials.gov Identifier: NCT03981055
• Other Study ID Numbers: 2018P002733
• First Posted: June 10, 2019
• Last Update Posted: August 16, 2022
• Last Verified: August 2022

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes

Additional relevant MeSH terms:

Parkinson Disease; Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases