A Phase 1/2 interventional study of 2-MHz transcranial Doppler ultrasound and 2-MHz transcranial Doppler ultrasound insonation in Stroke, sponsored by The University of Texas Health Science Center, Houston. Completed at 2 sites in United States. Open to participants aged 18 Years and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2016-05-23.
Sponsored by The University of Texas Health Science Center, Houston · Phase 1/2, Interventional, and Treatment
The purpose of CLOTBUST-HF is to determine the safety of a novel, external Hands-Free transcranial Doppler (TCD) ultrasound system in healthy volunteers and ischemic stroke patients. If found to be safe, the widespread use of operator-independent, ultrasound-enhanced thrombolysis will allow the planning for a large Phase III efficacy trial.
Ultrasound energy to enhance intravenous rt-PA thrombolysis is a promising novel treatment modality for ischemic stroke. Despite encouraging safety data utilizing diagnostic frequencies of transcranial Doppler (TCD) ultrasound, lack of widespread availability of trained personnel has limited its application.
- The primary specific aim for this pilot phase I/II study is to assess the safety of a novel, external Hands-Free TCD ultrasound system. Safety of the new Hands-Free TCD system will first be assessed in healthy volunteers. Safety in these participants will be determined by detailed neurological and dermatological exams and MRI imaging of the brain. Next, safety of the device will be evaluated in two distinct sets of acute ischemic stroke patients: 0-3 hour patients treated with standard IV rt-PA and 3-6 hour non-lytic, image-selected patients treated with sonolysis (with or without intravenous microbubbles). Among the healthy volunteers the primary measures of safety will be to have no detectable changes in a detailed neurological exam nor any blood- brain barrier (BBB) disruption or changes in permeability. Among both the 0-3 hour and 3-6 hour groups the primary measure of safety will be to not tolerate greater than a 10% rate of symptomatic intracerebral hemorrhage (sICH) within 24 hours.
* The primary hypothesis is that replacing conventional TCD ultrasound hand-held TCD technology with a Hands-Free system will be safe in healthy volunteers as well as acute ischemic stroke patients.
If the device is found to be safe in either the 0-3 hour or 3-6 hour groups,
- the secondary aims for this study will explore the rates of arterial recanalization in the 0-3 hour and/or 3-6 hour groups, favorable outcomes, and clinical recovery. The secondary aims will assess the hypothesis is that Hands-Free TCD will display similar recanalization and early clinical recovery rates compared to available historical diagnostic TCD ultrasound controls exposed to conventional FDA-approved TCD technology.
Data generated during this phase I/II trial will evaluate the safety of replacing an operator-dependent TCD device with an operator-independent unit. In turn, this will allow extensive availability of therapeutic ultrasound and improve enrollment into ultrasound-enhanced thrombolysis stroke trials.
7,441 studies on the registry are indexed under Stroke; 2,012 are open to participants now.
This study's enrollment of 35 is below the median of 50 across 5,482 interventional studies indexed under Stroke.
Browse Stroke studies →The University of Texas Health Science Center, Houston is the lead sponsor of 897 studies on the registry; 214 are open to participants now.
Of its 173 completed or terminated interventional studies of FDA-regulated products, 142 (82%) have results posted.
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Phase I Safety (healthy volunteers):
Phase II (0-3 hours ischemic stroke patients):
Phase II (3-6 hours ischemic stroke patients):
Presence of neuroimaging defined mismatch (CT or MRI prior to enrollment)
CT-perfusion
MRI Diffusion-Perfusion mismatch
EXCLUSION CRITERIA:
Phase I Safety (healthy volunteers):
Phase II (0-3 hours ischemic stroke patients):
Subjects without history of Central Nervous System Disease will receive 2-hours of hands-free 2-megahertz (MHz) transcranial Doppler ultrasound insonation continuously. A brain MRI with gadolinium will be performed before and after the ultrasound.
Device: 2-MHz transcranial Doppler ultrasound
Ischemic stroke patients who present between 0-3 hours will receive 2-hours of hands-free 2-MHz transcranial Doppler ultrasound Continuously to the intracranial vessels.
Device: 2-MHz transcranial Doppler ultrasound insonation
2-hours of hands-free ultrasound will be insonated continuously. A brain MRI with gadolinium will be performed before and after the ultrasound.
Also known as: transcranial Doppler Ultrasound, ultrasound
2-hours of hands-free ultrasound delivered to in the intracranial vessels.
Also known as: transcranial Doppler ultrasound, ultrasound, sonothrombolysis
Number of Participants in Phase I Group With Blood-brain-barrier Disruption (BBB) as Measured by MRI of the Brain
Phase I : Imaging of the brain via MRI scans was performed to determine if the Hands-Free transcranial Doppler (TCD) system results in any BBB-disruption or deterioration in permeability.
Time frame: 2-3 hours after treatment
Safety in Phase II Group as Measured by Incidence of Symptomatic Intracerebral Hemorrhage
Phase II: Determine if the Hands-Free TCD will not result in higher than 10% rate of symptomatic intracerebral hemorrhage (ICH) within 24 hours (defined as clinical worsening \> 4 NIH Stroke Scale (NIHSS) points and presence of hemorrhage on CT scan that in the opinion of the treating physician is causatively related to ICH on CT) in 0-3 hours acute stroke patients treated with intravenous tissue-type plasminogen activator (IV-t-PA).
Time frame: within 24 hours
Number of Participants in Phase I Group With Neurological Deterioration as Measured by Neurological Examination
The neurological examinations comprised assessments of mental status and orientation, cranial nerve examination, muscle strength and tone, deep tendon reflexes, sensory testing, coordination, and gait.
Time frame: 2-3 hours after treatment
Number of Participants in Phase I Group With Adverse Events During and After Study Treatment With HF TCD
Phase I - A group of healthy volunteers will be assessed to determine the feasibility and activity of hands-free (HF) transcranial Doppler (TCD). Adverse events include subject complaints regarding discomfort of the device and dermatological adverse events as evidenced by a detailed physical examination of skin integrity post-insonation.
Time frame: 2-3 hours after treatment
Percentage of Participants in the Phase II Group That Show Arterial Recanalization as Measured Using Standard Transcranial Doppler Ultrasound Systems
Ischemic stroke patients: 2-hour rates of arterial complete and partial recanalization as measured using standard Transcranial Doppler Ultrasound systems.
Time frame: 2-3 hours after treatment
Percentage of Participants in Phase II Group With Neurological Worsening as Determined by the NIH Stroke Scale
The National Institutes of Health Stroke Scale, or NIH Stroke Scale (NIHSS) is a tool used by healthcare providers to objectively quantify the impairment caused by a stroke. Each item on the NIHSS scores a specific ability between a 0 and 4. For each item, a score of 0 typically indicates normal function in that specific ability, while a higher score is indicative of some level of impairment. The individual scores from each item are summed in order to calculate a patient's total NIHSS score. The maximum possible score is 42, with the minimum score being a 0.
Time frame: within 90 days of enrollment
Percentage of Participants in Phase II Group With Excellent Outcome as Measured by Modified Rankin Scale (mRS)
A modified Rankin Scale (mRS) score of 0 or 1 indicates an excellent outcome. The mRS is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. The mRS scale ranks patients from 0 to 6 (0 is the best score, 6 is the worst score).
Time frame: at 3-months from enrollment
| Milestone | Phase I | Phase II |
|---|---|---|
| Started | 18 | 20 |
| Completed | 15 | 20 |
| Not completed | 3 | 0 |
| Withdrew: Withdrawal by subject | 2 | 0 |
| Withdrew: Mri contraindication | 1 | 0 |
Phase I : Imaging of the brain via MRI scans was performed to determine if the Hands-Free transcranial Doppler (TCD) system results in any BBB-disruption or deterioration in permeability.
| participants | Phase I |
|---|---|
| Number of Participants in Phase I Group With Blood-brain-barrier Disruption (BBB) as Measured by MRI of the Brain | 0 |
Phase II: Determine if the Hands-Free TCD will not result in higher than 10% rate of symptomatic intracerebral hemorrhage (ICH) within 24 hours (defined as clinical worsening \> 4 NIH Stroke Scale (NIHSS) points and presence of hemorrhage on CT scan that in the opinion of the treating physician is causatively related to ICH on CT) in 0-3 hours acute stroke patients treated with intravenous tissue-type plasminogen activator (IV-t-PA).
| percentage of patients | Phase II - Ischemic Stroke Patients |
|---|---|
| Safety in Phase II Group as Measured by Incidence of Symptomatic Intracerebral Hemorrhage | 0 (0 to 17) |
Phase I - A group of healthy volunteers will be assessed to determine the feasibility and activity of hands-free (HF) transcranial Doppler (TCD). Adverse events include subject complaints regarding discomfort of the device and dermatological adverse events as evidenced by a detailed physical examination of skin integrity post-insonation.
| participants | Phase 1 (Healthy Volunteers) |
|---|---|
| Number of Participants in Phase I Group With Adverse Events During and After Study Treatment With HF TCD | 0 |
Ischemic stroke patients: 2-hour rates of arterial complete and partial recanalization as measured using standard Transcranial Doppler Ultrasound systems.
| percentage of patients | Phase II - Iscehmic Stroke Patients |
|---|---|
| Percentage of Participants in the Phase II Group That Show Arterial Recanalization as Measured Using Standard Transcranial Doppler Ultrasound Systems | 40 (19 to 64) |
The National Institutes of Health Stroke Scale, or NIH Stroke Scale (NIHSS) is a tool used by healthcare providers to objectively quantify the impairment caused by a stroke. Each item on the NIHSS scores a specific ability between a 0 and 4. For each item, a score of 0 typically indicates normal function in that specific ability, while a higher score is indicative of some level of impairment. The individual scores from each item are summed in order to calculate a patient's total NIHSS score. The maximum possible score is 42, with the minimum score being a 0.
| percentage of patients | Phase II - Ischemic Stroke Patients |
|---|---|
| Percentage of Participants in Phase II Group With Neurological Worsening as Determined by the NIH Stroke Scale | 5 (0 to 25) |
A modified Rankin Scale (mRS) score of 0 or 1 indicates an excellent outcome. The mRS is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. The mRS scale ranks patients from 0 to 6 (0 is the best score, 6 is the worst score).
| percentage of patients | Phase II - Ischemic Stroke Patients |
|---|---|
| Percentage of Participants in Phase II Group With Excellent Outcome as Measured by Modified Rankin Scale (mRS) | 25 (7 to 49) |
The neurological examinations comprised assessments of mental status and orientation, cranial nerve examination, muscle strength and tone, deep tendon reflexes, sensory testing, coordination, and gait.
| participants | Phase I: Healthy Volunteers |
|---|---|
| Number of Participants in Phase I Group With Neurological Deterioration as Measured by Neurological Examination | 0 |
Non-serious events are listed at a 3% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Phase I: Healthy Volunteers | — | 0/15 (0%) | 0/15 (0%) |
| Phase II - Ischemic Stroke Patients | — | 9/20 (45%) | 19/20 (95%) |
| Event | Phase I: Healthy Volunteers | Phase II - Ischemic Stroke Patients |
|---|---|---|
| Cerebral edemaNervous system disorders | 0/15 | 4/20 |
| Pneumonia/respiratory failureRespiratory, thoracic and mediastinal disorders | 0/15 | 4/20 |
| DeathNervous system disorders | 0/15 | 3/20 |
| Intracranial hemohhrage secondary to bacterial endocarditisNervous system disorders | 0/15 | 1/20 |
| SepsisInfections and infestations | 0/15 | 1/20 |
| Stroke progression/Nuero-worseningNervous system disorders | 0/15 | 1/20 |
| Event | Phase I: Healthy Volunteers | Phase II - Ischemic Stroke Patients |
|---|---|---|
| FewerInfections and infestations | 0/15 | 6/20 |
| Anemia/decreased hemoglobin and hematocritBlood and lymphatic system disorders | 0/15 | 6/20 |
| HypertensionCardiac disorders | 0/15 | 6/20 |
| Asymptomatic ICHNervous system disorders | 0/15 | 6/20 |
| Elevated white blood countInfections and infestations | 0/15 | 5/20 |
| TachycardiaCardiac disorders | 0/15 | 4/20 |
| TachypneaRespiratory, thoracic and mediastinal disorders | 0/15 | 4/20 |
| BradycardiaCardiac disorders | 0/15 | 2/20 |
| Utinary tract infectionInfections and infestations | 0/15 | 2/20 |
| HypotensionCardiac disorders | 0/15 | 1/20 |
| Age, Categorical(Participants) | Phase I | Phase II | Total |
|---|---|---|---|
| <=18 years | 0 | 0 | 0 |
| Between 18 and 65 years | 13 | 12 | 25 |
| >=65 years | 2 | 8 | 10 |
| Age, Continuous(years) | Phase I | Phase II | Total |
|---|---|---|---|
| Mean | 49 ± 16 | 63 ± 14 | 57 ± 17 |
| Sex: Female, Male(Participants) | Phase I | Phase II | Total |
|---|---|---|---|
| Female | 9 | 8 | 17 |
| Male | 6 | 12 | 18 |
| Region of Enrollment(participants) | Phase I | Phase II | Total |
|---|---|---|---|
| United States | 15 | 20 | 35 |
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