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StrokePhase 1/2CLOTBUST-HFNCT01240356

CLOTBUST Hands-Free: A Phase I/II Pilot Safety Trial

A Phase 1/2 study testing 2-MHz transcranial Doppler ultrasound and 2-MHz transcranial Doppler ultrasound insonation in people with Stroke, run by The University of Texas Health Science Center, Houston at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and olderHealthy volunteers can take part
Conditions the study is for
Stroke
What is being tested?
2-MHz transcranial Doppler ultrasound and 2-MHz transcranial Doppler ultrasound insonation
Type of treatment
Medical device
Could I receive a placebo?
No, everyone receives an active treatment
How many people
35 participants
Where
2 sitesUnited States
Study dates
Dec 2008to Oct 2013
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • Phase I Safety (healthy volunteers):
  • Presence of temporal windows as measured first by an FDA-approved diagnostic TCD device.
  • Age ≥ 18 years old.
  • Signed informed consent.
  • Phase II (0-3 hours ischemic stroke patients):
  • Disabling focal neurological deficit (NIHSS > 4 points);
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  • No evidence of hemorrhage on non-contrast head CT scan;
  • Intravenous rt-PA (0.9 mg/kg, 10% bolus 90% infusion over 1 hour, maximum dose 90 mg) infusion initiated within 3 hours of symptom onset;
  • Diagnostic TCD completed and HF-TCD placed before rt-PA bolus.
  • Diagnostic TCD confirms intracranial arterial occlusion of the middle cerebral artery (MCA), anterior cerebral artery (ACA), internal carotid artery (ICA), posterior cerebral artery (PCA) or distal basilar artery.
  • Age ≥ 18 years old.
  • Signed informed consent.
  • Phase II (3-6 hours ischemic stroke patients):
  • Measurable focal neurological deficit (NIHSS > 4 points);
  • No evidence of hemorrhage on non-contrast head CT scan;
  • Diagnostic TCD confirms intracranial arterial occlusion of the middle cerebral artery (MCA), anterior cerebral artery (ACA), internal carotid artery (ICA), posterior cerebral artery (PCA) or distal basilar artery.
  • Presence of neuroimaging defined mismatch (CT or MRI prior to enrollment)
  • CT-perfusion
  • ≥ 20% difference between affected territories on Time to Peak (TTP) and Cerebral Blood Volume (CBV) maps.
  • MRI Diffusion-Perfusion mismatch
  • ≥ 20% difference between diffusion-weighted imaging (DWI) lesion and territory of perfusion delay perfusion weighted imaging (PWI).
  • Age ≥ 18 years old.
  • Signed informed consent.

Who cannot join

  • Phase I Safety (healthy volunteers):
  • History of any neurological disease affecting the central nervous system;
  • Lack of temporal windows.
  • History of renal disease or glomerular filtration rate (GFR) < 60.
  • Contraindication to MRI (e.g., pacemaker, spinal cord stimulator, severe claustrophobia)
  • Phase II (0-3 hours ischemic stroke patients):
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  • Absent temporal windows in patients with anterior circulation ischemia;
  • Intra-arterial thrombolysis;
  • Patient refusal to give informed consent to participate in the CLOTBUST-HF trial;
  • Contraindications for intravenous rt-PA (NINDS rt-PA Stroke Study Protocol)2.
  • Phase II (3-6 hours ischemic stroke patients):
  • Absent temporal windows in patients with anterior circulation ischemia;
  • Intra-arterial thrombolysis;
  • Patient refusal to give informed consent to participate in the CLOTBUST-HF trial;
  • History of allergic response to Definity® microspheres or microbubbles currently being tested (MRX-801);
  • Baseline imaging consistent with a malignant ischemic pattern (low CBV values or DWI territory >100cc of tissue);
  • Baseline MRI imaging demonstrating delayed perfusion of > 8 seconds in >100cc of brain parenchyma26;
  • Patients receiving other investigational drugs, procedures, or therapies within 30 days prior to study treatment;
  • Significant concurrent medical/neurological conditions or deviation from normal laboratory test values at baseline that, in the opinion of the investigator, pose significant risk to the patient and warrant exclusion from the study;
  • Known severe chronic obstructive pulmonary disease (COPD) (baseline oxygen saturation < 80% on room air);
  • Known right-to-left cardiac shunt.

Trial locations and contacts

2 sites in 1 country.

United States2 sites
  • University of Alabama Birmingham

    Birmingham, Alabama, 35233

  • UT Medical School-Houston

    Houston, Texas, 77030

Other trials in United States

About this study

Official title: Combined Lysis of Thrombus in Brain Ischemia With Transcranial Ultrasound and Systemic T-PA-Hands-Free. A Phase I/II Pilot Safety Trial

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.

Read the detailed description

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.

Conditions
Stroke
Being tested
2-MHz transcranial Doppler ultrasound, 2-MHz transcranial Doppler ultrasound insonation
Keywords
transcranial doppler, sonothrombolysis, ultrasound, stroke
Medical subject headings
Stroke

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • 2-MHz transcranial Doppler ultrasoundDevice

    Also called transcranial Doppler Ultrasound, ultrasound

    2-hours of hands-free ultrasound will be insonated continuously. A brain MRI with gadolinium will be performed before and after the ultrasound.

  • 2-MHz transcranial Doppler ultrasound insonationDevice

    Also called transcranial Doppler ultrasound, ultrasound, sonothrombolysis

    2-hours of hands-free ultrasound delivered to in the intracranial vessels.

Study groups in NCT01240356
Study groupRoleWhat they receive
Phase I: Healthy VolunteersExperimentalSubjects 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.
Receives: Device: 2-MHz transcranial Doppler ultrasound
Phase II: 0-3 hour PatientsExperimentalIschemic 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.
Receives: Device: 2-MHz transcranial Doppler ultrasound insonation

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 2-3 hours after treatment

  2. 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).

    Measured: within 24 hours

  3. 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.

    Measured: 2-3 hours after treatment

Secondary outcomes (4)
  1. 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.

    Measured: 2-3 hours after treatment

  2. 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.

    Measured: 2-3 hours after treatment

  3. 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.

    Measured: within 90 days of enrollment

  4. 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).

    Measured: at 3-months from enrollment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Nov 2010 (estimated)
  2. Study startDec 2008
  3. Primary completionOct 2013
  4. Study completionOct 2013

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
35 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01240356
Sponsor's protocol ID
CLOTBUST-HF
Acronym
CLOTBUST-HF
Status last verified
May 2016
First submitted
8 Nov 2010
Last updated
23 May 2016
Data monitoring committee
Yes

Publications

  • Barlinn K, Barreto AD, Sisson A, Liebeskind DS, Schafer ME, Alleman J, Zhao L, Shen L, Cava LF, Rahbar MH, Grotta JC, Alexandrov AV. CLOTBUST-hands free: initial safety testing of a novel operator-independent ultrasound device in stroke-free volunteers. Stroke. 2013 Jun;44(6):1641-6. doi: 10.1161/STROKEAHA.113.001122. Epub 2013 Apr 18.

    PubMed 23598523
  • Barreto AD, Alexandrov AV, Shen L, Sisson A, Bursaw AW, Sahota P, Peng H, Ardjomand-Hessabi M, Pandurengan R, Rahbar MH, Barlinn K, Indupuru H, Gonzales NR, Savitz SI, Grotta JC. CLOTBUST-Hands Free: pilot safety study of a novel operator-independent ultrasound device in patients with acute ischemic stroke. Stroke. 2013 Dec;44(12):3376-81. doi: 10.1161/STROKEAHA.113.002713. Epub 2013 Oct 24.

    PubMed 24159060
  • Al-hussain F, Hussain MS, Molina C, Uchino K, Shuaib A, Demchuk AM, Alexandrov AV, Saqqur M; CLOTBUST Investigators. Does the sex of acute stroke patients influence the effectiveness of rt-PA? BMC Neurol. 2014 Mar 26;14:60. doi: 10.1186/1471-2377-14-60.

    PubMed 24669960

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing 2-MHz transcranial Doppler ultrasound and 2-MHz transcranial Doppler ultrasound insonation in people with Stroke, run by The University of Texas Health Science Center, Houston at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 23 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 23 May 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 23 May 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants in Phase I Group With Blood-brain-barrier Disruption (BBB) as Measured by MRI of the Brain (time frame: 2-3 hours after treatment). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01240356, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 May 2016.

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