Safety of Rt-PA + Transcranial Emission of Low-Energy Lasers for Acute Stroke Recovery

NCT ID: NCT01220739

Last Updated: 2016-12-05

Study Results

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE2

Total Enrollment

12 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-06-30

Study Completion Date

2013-04-30

Brief Summary

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To assess the safety and preliminary efficacy of combining intravenous rt-PA with transcranial laser therapy (TLT) with the NeuroThera® Laser System (referred to hereafter as NTS) in subjects treated for acute ischemic stroke. Treatment with IV rt-PA must begin within 3 hours of symptom onset, and the initiation of TLT procedure must be feasible for each subject within 6 hours of stroke onset. The NeuroThera® Laser System is an investigational device that provides noninvasive transcranial laser therapy to subjects diagnosed with acute ischemic stroke. The wavelength of the laser light is in the infrared zone of the electromagnetic spectrum and is invisible to the naked eye.

Detailed Description

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This study is a phase II (n= 200), prospective, double-blind, randomized, sham-controlled, multicenter, safety study of intravenous (IV) rt-PA alone versus IV rt-PA plus TLT (Transcranial Laser Therapy) at approximately 10 investigational sites (United States only). The primary endpoint for this safety study is occurrence of symptomatic intracranial hemorrhages at 36 - 48 hours after stroke symptom onset.

Symptomatic hemorrhage will be defined as deterioration of more than 4 points on the NIHSS lasting at least 72 hours accompanied by intracranial hemorrhage in the distribution of the neurological deficit as identified by neuroimaging scans. All follow up neuroimaging scans will be reviewed centrally by an independent reviewer for the presence or absence of hemorrhage on the 36-48 hour scan.

The secondary endpoints for this study are as follows:

* Hemorrhagic transformation without clinical consequences (asymptomatic) within 36-48 hours. All follow-up neuroimaging scans will be reviewed centrally by an independent reviewer for the presence or absence of hemorrhage on the 36-48 hour scan.
* Mortality
* The modified Rankin Scale (mRS) score dichotomized as 0-1 versus an mRS score of 2-6 at 90 days or the last rating in patients that develop intracerebral hemorrhages
* Frequency of SAEs and AEs This study is a phase II (N = 200), prospective, double-blind, randomized, sham controlled, multicenter, safety study of intravenous (IV) tissue plasminogen activator (rt-PA) versus IV rt-PA plus transcranial laser therapy (TLT) at approximately 10 investigational sites.

The study population will be randomized into two arms. One group will receive a sham TLT procedure (Sham Control Group or SCG) and the second group will receive an active TLT procedure (TLTG).

The randomization ratio of SCG and TLTG will be 1:1 and will be stratified in order to ensure balanced subject distribution between the treatment and sham-controlled groups for the following factors:

* Stroke severity as measured by National Institute of Health Stroke Scale (NIHSS) at baseline (stratified as 7-9, 10-13, 14-17)
* Study Site There are 6 visits in the study. The purpose of the Visit 1 will be to determine and confirm the eligibility of patients for participation in the StELLAR Study and document baseline information about the subject and their stroke event. This will include all of the following standard of care tests and procedures: a non contrast head CT scan performed prior to rt-PA administration, vital signs, height , weight ,physical exam, finger stick or blood glucose, serum or urine pregnancy test (if women of childbearing potential). In addition, the following data will be obtained: prestroke mRS, NIHSS, presumed location of stroke and vascular territory, start and stop date and time of the IV rt-PA treatment and dose given, date and time of stroke onset, date and time of arrival to the hospital, demographic data (date of birth, gender, ethnicity),sociodemographic data (education, marital status, social support prior to stroke),medical and surgical history (specific cardiovascular, neurological, endocrine, and other standard questions asked), method of contraception use (for women of child bearing potential), prior (three days prior to Screening) and current concomitant medication use, smoking history, adverse events from the time of obtaining informed consent. To be eligible for the study, the administration of rt-PA should follow the guidelines outlined by the National Institutes of Neurologic Disorders. Patients meeting the inclusion/exclusion criteria will be enrolled into the study after written informed consent is obtained by the patient or their legally authorized representative.

Conditions

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Ischemic Stroke

Keywords

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ischemic stroke transcranial laser tissue plasminogen activator therapy

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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IV tPA + Sham Transcranial Laser Therapy

Subjects in this treatment arm will receive IV tPA within 3 hours of stroke symptom onset followed by sham transcranial laser therapy no sooner than 12 hours after tPA and no greater than 24 hours from stroke onset.

Group Type SHAM_COMPARATOR

Transcranial Laser Therapy

Intervention Type DEVICE

Transcranial laser therapy is administered with the NeuroThera® Laser System (NTS) in subjects diagnosed with acute ischemic stroke. A laser system is a medical instrument that concentrates energy light on an area. Laser treatment has been used to deliver intense light energy to aid in the healing of tissues and wounds. The transcranial laser treatment procedure consists of applying the NTS laser to twenty different sites on the skull for two minutes at each site.

IV tPA +Transcranial Laser Therapy

Subjects in this treatment arm will receive IV tPA within 3 hours of stroke symptom onset followed by transcranial laser therapy no sooner than 12 hours after tPA and no greater than 24 hours from stroke onset.

Group Type ACTIVE_COMPARATOR

Transcranial Laser Therapy

Intervention Type DEVICE

Transcranial laser therapy is administered with the NeuroThera® Laser System (NTS) in subjects diagnosed with acute ischemic stroke. A laser system is a medical instrument that concentrates energy light on an area. Laser treatment has been used to deliver intense light energy to aid in the healing of tissues and wounds. The transcranial laser treatment procedure consists of applying the NTS laser to twenty different sites on the skull for two minutes at each site.

Interventions

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Transcranial Laser Therapy

Transcranial laser therapy is administered with the NeuroThera® Laser System (NTS) in subjects diagnosed with acute ischemic stroke. A laser system is a medical instrument that concentrates energy light on an area. Laser treatment has been used to deliver intense light energy to aid in the healing of tissues and wounds. The transcranial laser treatment procedure consists of applying the NTS laser to twenty different sites on the skull for two minutes at each site.

Intervention Type DEVICE

Other Intervention Names

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TLT NeuroThera Laser System (NTS)

Eligibility Criteria

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Inclusion Criteria

Subjects may be included in the study only if they meet all of the following criteria:

1. Subject is at least 40 years of age at screening, but has not had their 81st birthday.
2. Subject has received IV rt-PA per the NINDS rt-PA Protocol Guidelines within 3 hours of symptom onset for an acute ischemic stroke.
3. Subject is diagnosed with acute ischemic stroke and presents to the health care facility at a time such that initiation of NTS procedure is feasible within 6 hours of the time of stroke onset. The time of stroke onset is defined as the time at which a change in the baseline neurological function occurred. If the time is not known (e.g., the subject awakens from sleep with new symptoms), the last time the patient was observed to be neurologically intact must be considered to be the time of onset.
4. Documented baseline NIHSS score of \> 7 and \< 17 prior to IV rt-PA administration. Subjects who transfer from other facilities after receiving IV rt-PA must have a documented NIHSS by a certified examiner prior to initiation of rt-PA treatment. Documentation of NIHSS score via telemedicine is acceptable if performed by a certified examiner. Subjects who improve prior to NTS procedure will still be treated, unless their NIHSS improves to 0.
5. Full functional independence just prior to the present stroke episode as defined by the following criteria:

* Estimated prestroke mRS score 0 or 1.
* Ambulates independently, may need a cane or walker, but does not need the assistance of another person.
* Absence of a medical/physical/mental condition that substantially limits the subject's ability to work, study, participate in leisure activities, or look after family at home
* Completely independent, does not need supervision (may live with other individuals, but could live alone if necessary)
6. Negative serum or urine pregnancy test in females of childbearing potential.
7. Subject (or legally authorized representative) provides written Informed Consent in compliance with local regulations prior to enrollment into this study.
8. The subject (and caregiver, if applicable) is willing to participate in this study for at least 90 days after the onset of stroke.-

Exclusion Criteria

1. Evidence on from a pre-tPA head CT of an intracranial, subdural, or subarachnoid hemorrhage or clinical presentation suggestive of subarachnoid hemorrhage even if the initial neuroimaging scan is normal.
2. Clinical presentation consistent with a brainstem or cerebellar stroke
3. A rapidly improving neurological status that in the opinion of the investigator will make the subject unsuitable for participation in this study or patient rapidly improves to NIHSS of 0 by start of NTS procedure.
4. The subject had a seizure at stroke onset or within the 7 days prior to stroke onset.
5. Sustained blood glucose \> 300 mg/dl or \< 60 mg/dl
6. Subjects who, on repeated measurement, have a systolic blood pressure \> 185, or a diastolic blood pressure \> 110mmHg, post rt-PA administration, or it is the opinion of the investigator that aggressive treatment to reduce blood pressure post thrombolysis is required to keep pressure within these limits.
7. Presumed and/or confirmed septic embolus.
8. The subject has a history of CNS vascular wall disease (e.g. aneurysm, AVM).
9. The subject has a history of CNS disease or damage (e.g. neoplasm or dementia) which may influence the subject's outcome assessment.
10. The subject has a significant skin condition (i.e., hemangioma, scleroderma, psoriasis, rash, open wound or tattoo) on their scalp that is found to be directly below three or more TLT procedure sites.
11. Planned or actual use of any intra-arterial thrombolytic medication or a clot retrieval device, or any diagnostic or therapeutic interventional neurovascular procedure, including mechanical recanalization, whether successful or unsuccessful, during this stroke episode.
12. Subject previously participated in another investigational drug or device trial within the preceding four weeks.
13. Subject is a female who is pregnant or lactating (within the previous 30 days),or who is of child-bearing potential unless she is surgically sterile or she and/or her partner are using a medically acceptable method of birth control.
14. The subject has an implant of any kind in the head (i.e. clipped aneurysm, embolised AVM, implantable shunt - Hakim valve).
15. Any use of light-activated drugs (photodynamic therapy) within 14 days prior to study enrollment.
16. The subject participated in the NEST-1, NEST-2, or NEST-3 Study.
17. The subject has any co-existing or terminal disease that may limit life expectancy or any medical condition (e.g. morbid obesity, substance abuse) that may, in the clinical judgment of the Investigator, independently influence the subject's outcome during the course of the study.
18. The subject is otherwise determined, based on the opinion of the Investigator,to be an unsuitable candidate for enrollment in this study. -
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institute of Neurological Disorders and Stroke (NINDS)

NIH

Sponsor Role collaborator

University of California, San Diego

OTHER

Sponsor Role lead

Responsible Party

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Justin Zivin

Professor, Department of Neurosciences

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Thomas Hemmen, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of California, San Diego

Locations

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Swedish Medical Center

Englewood, Colorado, United States

Site Status

Palmetto Health Richland

Columbia, South Carolina, United States

Site Status

Providence Medical Research Center

Spokane, Washington, United States

Site Status

Countries

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United States

References

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Zivin JA, Albers GW, Bornstein N, Chippendale T, Dahlof B, Devlin T, Fisher M, Hacke W, Holt W, Ilic S, Kasner S, Lew R, Nash M, Perez J, Rymer M, Schellinger P, Schneider D, Schwab S, Veltkamp R, Walker M, Streeter J; NeuroThera Effectiveness and Safety Trial-2 Investigators. Effectiveness and safety of transcranial laser therapy for acute ischemic stroke. Stroke. 2009 Apr;40(4):1359-64. doi: 10.1161/STROKEAHA.109.547547. Epub 2009 Feb 20.

Reference Type BACKGROUND
PMID: 19233936 (View on PubMed)

Hacke W, Schellinger PD, Albers GW, Bornstein NM, Dahlof BL, Fulton R, Kasner SE, Shuaib A, Richieri SP, Dilly SG, Zivin J, Lees KR; NEST 3 Committees and Investigators. Transcranial laser therapy in acute stroke treatment: results of neurothera effectiveness and safety trial 3, a phase III clinical end point device trial. Stroke. 2014 Nov;45(11):3187-93. doi: 10.1161/STROKEAHA.114.005795. Epub 2014 Oct 7.

Reference Type BACKGROUND
PMID: 25293665 (View on PubMed)

Huisa BN, Stemer AB, Walker MG, Rapp K, Meyer BC, Zivin JA; NEST-1 and -2 investigators. Transcranial laser therapy for acute ischemic stroke: a pooled analysis of NEST-1 and NEST-2. Int J Stroke. 2013 Jul;8(5):315-20. doi: 10.1111/j.1747-4949.2011.00754.x. Epub 2012 Feb 2.

Reference Type BACKGROUND
PMID: 22299818 (View on PubMed)

Other Identifiers

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P50NS044148

Identifier Type: NIH

Identifier Source: secondary_id

View Link

StELLAR

Identifier Type: -

Identifier Source: org_study_id