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Feasibility Study of Transcranial Ultrasound Stimulation (TUS) on Stroke Patients

Primary Purpose

Intracerebral Hemorrhage, Hemiplegia

Status
Recruiting
Phase
Not Applicable
Locations
Taiwan
Study Type
Interventional
Intervention
Transcranial ultrasound stimulation and rehabilitation
Rehabilitation
Sponsored by
Cheng-Hsin General Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Intracerebral Hemorrhage

Eligibility Criteria

20 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Age between 20 and 65 years old
  • hemiplegia or hemiparesis
  • has a history of hypertension
  • a victim of first episode of hypertensive intracerebral hemorrhage at basal ganglion
  • 3 to 12 months after the episode of hypertensive intracerebral hemorrhage
  • medically stable
  • the blood flow of middle cerebral artery (M1) could be detected by transcranial doppler

Exclusion Criteria:

  • severe heart failure (New York Heart Association class 4)
  • severe angina pectoris (canadian cardiovascular society class 4)
  • chronic kidney disease stage 5
  • hepatic encephalopathy stage 2 or more advanced
  • uncontrolled diabetes mellitus in recent 6 months (HbA1c > 8.5)
  • combined with intraventricular hemorrhage causing hydrocephalus and underwent ventriculoperitoneal shunt placement surgery
  • high-dose radiation exposure in recent 1 year
  • blood flow of middle cerebral artery (M1) could be not be detected by transcranial doppler at either side
  • major psychological disease in recent 6 months (for example, uncontrolled depression, schizophrenia, and bipolar disease)
  • has evidence of any autoimmune disease, neurodegenerative disease (such as parkinsonism, Alzheimer's disease), or epilepsy
  • has clinically significant systemic disease or severe infection (pneumonia, sepsis)
  • pregnant or lactating women
  • allergy to MRI contrast
  • uncontrolled hypertension (systolic blood pressure higher than 160 mmHg or diastolic blood pressure higher than 100 mmHg) transcranial doppler
  • aneurysm, brain tumor, or arteriovenous malformation identified by MRA
  • has coagulation disorders or other coagulation problems identified by blood test (abnormal complete blood count, prothrombin time, or partial thromboplastin time)

Sites / Locations

  • Cheng-Hsin general hospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Transcranial ultrasound stimulation and rehabilitation

Rehabilitation

Arm Description

The investigators expect to enroll 10 people in the experimental group.

The investigators expect to enroll 10 people in the control group.

Outcomes

Primary Outcome Measures

Brain observation by image
The investigators would use Magnetic Resonance Image (MRI) to observe if there is brain atrophy, hemorrhage, or any other anatomical change in brain. Magnetic Resonance Angiography (MRA) would be used, too, to observe any change in intracerebral vessels or blood-brain barrier.

Secondary Outcome Measures

Body weight
As a safety parameter, the investigators would follow up body weight (in kilograms) of the subjects, to observe if there is a tendency to rise or descend.
respiratory rate
As a safety parameter, the investigators would follow up respiratory rate (in times per minute) of the subjects, to observe if there is a tendency to rise or descend.
blood pressure
As a safety parameter, the investigators would follow up blood pressure (in millimeter of mercury, mmHg) of the subjects, to observe if there is a tendency to rise or descend.
heart rate
As a safety parameter, the investigators would follow up heart rate (in times per minute) of the subjects, to observe if there is a tendency to rise or descend.
electrocardiogram
As a safety parameter, the investigators would follow up electrocardiogram of the subjects, to observe if some newly-onset pathological evidences occur. For example, ST segment elevation, ST segment dumping, Q wave, or left bundle branch block could be pathological findings.
Serum biomarkers: trophic factors
The investigators would measure serum brain-derived neurotrophic factor (BDNF) and serum vascular endothelial growth factor (VEGF) as the indicators as trophic factors. The changes of these biomarkers during the study would be evaluated.
Serum biomarkers: factors relating inflammatory response
The investigators would measure matrix metalloproteinase-9, S100 calcium-binding protein B, glial fibrillary acidic protein, and Interleukin, as the factors relating inflammatory response. The changes of these biomarkers during the study would be evaluated.
Serum biomarkers: neurodegeneration
The investigators would measure phosphorylated Tau, and β-amyloid, as the indicators of neurodegeneration. The changes of these biomarkers during the study would be evaluated.
Device and procedure related adverse events recording
Rate of adverse events following each treatment through end of study clinical evaluation
National Institutes of Health Stroke Scale (NIHSS)
National Institutes of Health Stroke Scale (NIHSS) is an objective scale for neurologic impairment of stoke. This scale includes 13 categories, with highest score of 3 or 4 and lowest score is 0, quantifying level of consciousness, best gaze, visual filed, facial palsy, motor function, limb ataxia, sensory function, language function, dysarthria, extinction/inattention. The maximum score is 42, which signifies severe stroke, while the minimum score is 0, meaning a normal exam.
Stroke Rehabilitation Assessment of Movement (STREAM)
Stroke Rehabilitation Assessment of Movement (STREAM) evaluate the recovery of voluntary movement and mobility post stroke in supine, sitting, and standing posture. It is composed of 30 items, measuring the upper limb voluntary movement, lower limb voluntary movements and basic mobility. A 3 point original scale (0~2) is used for upper and lower limb voluntary movement, and a 4 point original scale (0~3) is used for basic mobility. Higher scales means better motor performance.
Fugl-Meyer Assessment (FMA)
The Fugl-Meyer Assessment (FMA) assesses motor functioning, balance, sensation and joint functioning in patients with post-stroke hemiplegia. The investigators chose the domain of motor score for this study. The motor score ranges from 0 (hemiplegia) to 100 points (normal motor performance). Divided into 66 points for upper extremity and 34 points for the lower extremity.
Wolf Motor Function test (WMFT)
It is a 17-item measure used to quantify upper extremity functional limitations. It is comprised of 2 strength items and 15 timed task performance items, and the investigators choose the 15 timed task performance items for this study. The test yields 3 scores: a functional ability (FA) score, which quantifies quality of performance; a timed (time) score, quantifying speed of performance in seconds; and a grip strength (strength) score. The FA score uses a 6-point ordinal scale to rate movement quality on 15 items, where 0 indicates no attempt to use the more affected upper extremity and 5 indicates that movement of the affected upper extremity appears to be normal. The time score is the mean time to complete the same 15 items; scores were truncated at 120 seconds.
Berg Balance Scale (BBS)
Berg balance scale determines a patient's ability to safely balance during a series of predetermined tasks. It is a 14 item list with each item consisting of a five-point ordinal scale ranging from 0 to 4, with 0 indicating the lowest level of function and 4 the highest level of function.
Timed up-and-go test
Time up-and-go test assesses a person's mobility and requires both static and dynamic balance. During this test, a person should stand up from a chair and walk for 3 meters, turns around and walks back to the chair and sit down. The spent time was recorded.
Barthal index
The Barthel Index measures a person's performance in activities of daily living (ADL). Ten variables describing ADL and mobility are scored, a higher number being a reflection of greater ability to function independently. The Barthel Index consists of 10 items of mobility and self care ADL.
World Health Organization Quality of Life (WHOQOL-BREF)-Taiwan version
The World Health Organization Quality of Life (WHOQOL-BREF) is a 28-item instrument consisting of four domains: physical health (7 items), psychological health (6 items), social relationships (4 items), and environmental health (9 items); with another 2 items about general condition and overall quality of life. Each individual item of the WHOQOL-BREF is scored from 1 to 5 on a response scale, which is stipulated as a five-point ordinal scale. The scores are then transformed linearly to a 0-100-scale. The higher scores equals better quality of life.

Full Information

First Posted
April 27, 2021
Last Updated
March 5, 2023
Sponsor
Cheng-Hsin General Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT04877184
Brief Title
Feasibility Study of Transcranial Ultrasound Stimulation (TUS) on Stroke Patients
Official Title
Feasibility Study of Transcranial Ultrasound Stimulation (TUS) on Stroke Patients
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 8, 2021 (Actual)
Primary Completion Date
December 31, 2023 (Anticipated)
Study Completion Date
December 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Cheng-Hsin General Hospital

4. Oversight

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

5. Study Description

Brief Summary
Currently, the main treatment method for Intracerebral Hemorrhage (ICH) is medication or surgery. However, the effectiveness of medicines is moderate and there are several side effects. In this clinical trial, we would like to enhance the protein levels of brain derived neurotrophic factor in the brain by the transcranial ultrasound stimulation (TUS). By this technology, the symptoms of ICH could be alleviated and the side effects of medicines might be avoided. Preclinical trials have also shown that low-intensity pulsed ultrasound can alleviate the degree of neuroinflammation, neurodegeneration and significantly improve motor and cognitive deficits after brain injury. The purpose of this clinical trial is to evaluate the safety and feasibility of TUS for the treatment of patients with hypertensive intracerebral hemorrhage. The primary safety assessment indexes are brain magnetic resonance imaging (MRI) and brain magnetic resonance angiography (MRA). The secondary safety assessment indexes include weight, vital signs, electrocardiogram, general blood biochemical tests, adverse reaction events, and concurrent drug tracking. The feasibility assessment includes blood specific biomarker expression and neurological function & quality of life scales.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Intracerebral Hemorrhage, Hemiplegia

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
InvestigatorOutcomes Assessor
Allocation
Non-Randomized
Enrollment
20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Transcranial ultrasound stimulation and rehabilitation
Arm Type
Experimental
Arm Description
The investigators expect to enroll 10 people in the experimental group.
Arm Title
Rehabilitation
Arm Type
Active Comparator
Arm Description
The investigators expect to enroll 10 people in the control group.
Intervention Type
Device
Intervention Name(s)
Transcranial ultrasound stimulation and rehabilitation
Intervention Description
The participants in experimental group would received transcranial ultrasound stimulation and rehabilitation therapy. transcranial ultrasound stimulation: during 4 weeks rehabilitation: physiotherapy and occupational therapy (may combine with speech therapy and psychological therapy if needed)
Intervention Type
Device
Intervention Name(s)
Rehabilitation
Intervention Description
The participants in control group would received rehabilitation therapy. - rehabilitation: physiotherapy and occupational therapy (may combine with speech therapy and psychological therapy if needed)
Primary Outcome Measure Information:
Title
Brain observation by image
Description
The investigators would use Magnetic Resonance Image (MRI) to observe if there is brain atrophy, hemorrhage, or any other anatomical change in brain. Magnetic Resonance Angiography (MRA) would be used, too, to observe any change in intracerebral vessels or blood-brain barrier.
Time Frame
12 weeks
Secondary Outcome Measure Information:
Title
Body weight
Description
As a safety parameter, the investigators would follow up body weight (in kilograms) of the subjects, to observe if there is a tendency to rise or descend.
Time Frame
12 weeks
Title
respiratory rate
Description
As a safety parameter, the investigators would follow up respiratory rate (in times per minute) of the subjects, to observe if there is a tendency to rise or descend.
Time Frame
12 weeks
Title
blood pressure
Description
As a safety parameter, the investigators would follow up blood pressure (in millimeter of mercury, mmHg) of the subjects, to observe if there is a tendency to rise or descend.
Time Frame
12 weeks
Title
heart rate
Description
As a safety parameter, the investigators would follow up heart rate (in times per minute) of the subjects, to observe if there is a tendency to rise or descend.
Time Frame
12 weeks
Title
electrocardiogram
Description
As a safety parameter, the investigators would follow up electrocardiogram of the subjects, to observe if some newly-onset pathological evidences occur. For example, ST segment elevation, ST segment dumping, Q wave, or left bundle branch block could be pathological findings.
Time Frame
12 weeks
Title
Serum biomarkers: trophic factors
Description
The investigators would measure serum brain-derived neurotrophic factor (BDNF) and serum vascular endothelial growth factor (VEGF) as the indicators as trophic factors. The changes of these biomarkers during the study would be evaluated.
Time Frame
12 weeks
Title
Serum biomarkers: factors relating inflammatory response
Description
The investigators would measure matrix metalloproteinase-9, S100 calcium-binding protein B, glial fibrillary acidic protein, and Interleukin, as the factors relating inflammatory response. The changes of these biomarkers during the study would be evaluated.
Time Frame
12 weeks
Title
Serum biomarkers: neurodegeneration
Description
The investigators would measure phosphorylated Tau, and β-amyloid, as the indicators of neurodegeneration. The changes of these biomarkers during the study would be evaluated.
Time Frame
12 weeks
Title
Device and procedure related adverse events recording
Description
Rate of adverse events following each treatment through end of study clinical evaluation
Time Frame
12 weeks
Title
National Institutes of Health Stroke Scale (NIHSS)
Description
National Institutes of Health Stroke Scale (NIHSS) is an objective scale for neurologic impairment of stoke. This scale includes 13 categories, with highest score of 3 or 4 and lowest score is 0, quantifying level of consciousness, best gaze, visual filed, facial palsy, motor function, limb ataxia, sensory function, language function, dysarthria, extinction/inattention. The maximum score is 42, which signifies severe stroke, while the minimum score is 0, meaning a normal exam.
Time Frame
12 weeks
Title
Stroke Rehabilitation Assessment of Movement (STREAM)
Description
Stroke Rehabilitation Assessment of Movement (STREAM) evaluate the recovery of voluntary movement and mobility post stroke in supine, sitting, and standing posture. It is composed of 30 items, measuring the upper limb voluntary movement, lower limb voluntary movements and basic mobility. A 3 point original scale (0~2) is used for upper and lower limb voluntary movement, and a 4 point original scale (0~3) is used for basic mobility. Higher scales means better motor performance.
Time Frame
12 weeks
Title
Fugl-Meyer Assessment (FMA)
Description
The Fugl-Meyer Assessment (FMA) assesses motor functioning, balance, sensation and joint functioning in patients with post-stroke hemiplegia. The investigators chose the domain of motor score for this study. The motor score ranges from 0 (hemiplegia) to 100 points (normal motor performance). Divided into 66 points for upper extremity and 34 points for the lower extremity.
Time Frame
12 weeks
Title
Wolf Motor Function test (WMFT)
Description
It is a 17-item measure used to quantify upper extremity functional limitations. It is comprised of 2 strength items and 15 timed task performance items, and the investigators choose the 15 timed task performance items for this study. The test yields 3 scores: a functional ability (FA) score, which quantifies quality of performance; a timed (time) score, quantifying speed of performance in seconds; and a grip strength (strength) score. The FA score uses a 6-point ordinal scale to rate movement quality on 15 items, where 0 indicates no attempt to use the more affected upper extremity and 5 indicates that movement of the affected upper extremity appears to be normal. The time score is the mean time to complete the same 15 items; scores were truncated at 120 seconds.
Time Frame
12 weeks
Title
Berg Balance Scale (BBS)
Description
Berg balance scale determines a patient's ability to safely balance during a series of predetermined tasks. It is a 14 item list with each item consisting of a five-point ordinal scale ranging from 0 to 4, with 0 indicating the lowest level of function and 4 the highest level of function.
Time Frame
12 weeks
Title
Timed up-and-go test
Description
Time up-and-go test assesses a person's mobility and requires both static and dynamic balance. During this test, a person should stand up from a chair and walk for 3 meters, turns around and walks back to the chair and sit down. The spent time was recorded.
Time Frame
12 weeks
Title
Barthal index
Description
The Barthel Index measures a person's performance in activities of daily living (ADL). Ten variables describing ADL and mobility are scored, a higher number being a reflection of greater ability to function independently. The Barthel Index consists of 10 items of mobility and self care ADL.
Time Frame
12 weeks
Title
World Health Organization Quality of Life (WHOQOL-BREF)-Taiwan version
Description
The World Health Organization Quality of Life (WHOQOL-BREF) is a 28-item instrument consisting of four domains: physical health (7 items), psychological health (6 items), social relationships (4 items), and environmental health (9 items); with another 2 items about general condition and overall quality of life. Each individual item of the WHOQOL-BREF is scored from 1 to 5 on a response scale, which is stipulated as a five-point ordinal scale. The scores are then transformed linearly to a 0-100-scale. The higher scores equals better quality of life.
Time Frame
12 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age between 20 and 65 years old hemiplegia or hemiparesis has a history of hypertension a victim of first episode of hypertensive intracerebral hemorrhage at basal ganglion 3 to 12 months after the episode of hypertensive intracerebral hemorrhage medically stable the blood flow of middle cerebral artery (M1) could be detected by transcranial doppler Exclusion Criteria: severe heart failure (New York Heart Association class 4) severe angina pectoris (canadian cardiovascular society class 4) chronic kidney disease stage 5 hepatic encephalopathy stage 2 or more advanced uncontrolled diabetes mellitus in recent 6 months (HbA1c > 8.5) combined with intraventricular hemorrhage causing hydrocephalus and underwent ventriculoperitoneal shunt placement surgery high-dose radiation exposure in recent 1 year blood flow of middle cerebral artery (M1) could be not be detected by transcranial doppler at either side major psychological disease in recent 6 months (for example, uncontrolled depression, schizophrenia, and bipolar disease) has evidence of any autoimmune disease, neurodegenerative disease (such as parkinsonism, Alzheimer's disease), or epilepsy has clinically significant systemic disease or severe infection (pneumonia, sepsis) pregnant or lactating women allergy to MRI contrast uncontrolled hypertension (systolic blood pressure higher than 160 mmHg or diastolic blood pressure higher than 100 mmHg) transcranial doppler aneurysm, brain tumor, or arteriovenous malformation identified by MRA has coagulation disorders or other coagulation problems identified by blood test (abnormal complete blood count, prothrombin time, or partial thromboplastin time)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Wen-Shin Song
Phone
+886-2-28264400
Ext
2081
Email
ch6364@chgh.org.tw
Facility Information:
Facility Name
Cheng-Hsin general hospital
City
Taipei
Country
Taiwan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Wen-Shin Song
Phone
+886-2-28264400
Ext
2081
Email
ch6364@chgh.org.tw

12. IPD Sharing Statement

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Feasibility Study of Transcranial Ultrasound Stimulation (TUS) on Stroke Patients

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