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Interim Analysis
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| Name | Class |
|---|---|
| The City College of New York | OTHER |
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This proposal is a prospective, single-center, dose-escalation safety, tolerability, feasibility and potential efficacy study of transcranial direct current stimulation (tDCS) in acute stroke patients with substantial salvageable penumbra due to a large vessel occlusion before and after endovascular therapy.
This is a single-center, sham-controlled, dose-escalation study where cathodal tDCS is delivered to threatened but not yet irreversibly damaged (penumbral) tissue in patients with large vessel occlusion who are undergoing recanalization procedure. Patients will be randomized in a 3:1 design, to cathodal versus sham (control) stimulation, at each six designed dose tiers. The dose tiers will be increasing in both intensity and duration of the stimulation. All patients will be receiving the first dose (stimulation cycle) after the recanalization procedure and patients at dose tiers 5-6 will also be receiving stimulation cycles before the recanalization procedure begins.
The occurrence of symptomatic intracranial hemorrhage will determine the pace of the escalation through the dose tiers.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Stimulation arm | Experimental | Patients will be randomized to active treatment (C-tDCS) vs sham stimulation in a 3:1 ratio. There will be 6 dose tiers: Tier 1 - 1 mA, and Tier 2- 2 mA: Consist of a single stimulation cycle (20min) after the endovascular procedure (EVT) in patients with TICI<2c,3 and negative immediate post-EVT CT scan for definitive evidence of ICH. Tier 3 - 1 mA and Tier 4- 2mA consist of 2 treatment cycles after the EVT in patients with TICI<2c and 3, and negative immediate post-EVT CT scan for definitive evidence of ICH. Tier 5 - 1 mA and tier 6- 2 mA consist of 3 treatment cycles. The first cycle will be up to 20 min cycle, after initial imaging and prior to arterial puncture, the second and third cycles after EVT in patients with TICI<2c and 3 and negative immediate post-EVT CT scan for definitive evidence of ICH. |
|
| Sham arm | Sham Comparator | Patients in the sham stimulation arm at all the tiers will have the cap and electrodes in place, and sham switch moved but without delivery of electrical stimulation. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Transcranial Direct Current Stimulation (tDCS) | Device | 20 minutes of Cathodal tDCS after +/- before endovascular thrombectomy (EVT) |
|
| Measure | Description | Time Frame |
|---|---|---|
| Primary Safety Outcome- Number of Participants With Symptomatic Intracranial Hemorrhage (SICH) | Symptomatic intracranial hemorrhage (SICH) is defined as an increase of 4 or more points on the National Institute of Health Stroke Scale (NIHSS) total score within 24 hours of stimulation associated with parenchymal hematoma type 1 (PH1), parenchymal hematoma type 2 (PH2), remote intraparenchymal hemorrhage (RIH), subarachnoid hemorrhage (SAH), or intraventricular hemorrhage (IVH). The NIHSS is a 15-item neurologic examination stroke scale used to evaluate the effect of acute stroke on the levels of consciousness, language, neglect, visual-field loss, extraocular movement, motor strength, ataxia, dysarthria, and sensory loss. A trained observer rates the patent's ability to answer questions and perform activities. Ratings for each item are scored with 3 to 5 grades with 0 as normal, and there is an allowance for untestable items. Accordingly, 0 is the lowest and 42 is the highest total score possible. In the NIHSS, the higher the score, the more impaired a stroke patient is. | At 24-hour post-stimulation |
| Primary Tolerability Outcome-Number of Participants Completing the Protocol-assigned Stimulation | The percentage of the patients completing the protocol-assigned stimulation treatment with no intolerability. | After 5 minutes of stimulation period |
| Primary Feasibility Outcome- Assessing the Speed of Stimulation Implementation From Randomization. | The median times from randomization to bridging C-tDCS initiation and the time form end of endovascular thrombectomy procedure to adjunctive C-tDCS initiation in the last 10 enrolled patients. | Median time from randomization to tDCS initiation |
| Measure | Description | Time Frame |
|---|---|---|
| Secondary Safety Outcome-Number of Participants With Asymptomatic Intracranial Hemorrhage (AICH) | AICH is defined as intracranial hemorrhage not associated with National Institute of Health Stroke Scale (NIHSS) total score worsening of ≥ 4. The NIHSS is a 15-item neurologic examination stroke scale used to evaluate the effect of acute stroke on the levels of consciousness, language, neglect, visual-field loss, extraocular movement, motor strength, ataxia, dysarthria, and sensory loss. A trained observer rates the patent's ability to answer questions and perform activities. Ratings for each item are scored with 3 to 5 grades with 0 as normal, and there is an allowance for untestable items. Accordingly, 0 is the lowest and 42 is the highest total score possible. In the NIHSS, the higher the score, the more impaired a stroke patient is. |
| Measure | Description | Time Frame |
|---|---|---|
| Exploratory Imaging Efficacy Outcome- Assessing Imaging Biomarker of Neuroprotection and Collateral Enhancement | By comparing the baseline MR/CT imaging with the MR/CT imaging at 2-hour (early) and 24-hour (final) post-stimulation, the following were planned to be measured: 1) Final penumbra salvage proportion, 2) Final hypoperfusion lesion reduction, 3) Early relative quantitative cerebral blood volume (qrCBV) enhancement. |
Inclusion criteria
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of California- Los Angeles (UCLA) | Los Angeles | California | 90095 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | Active Stimulation Arm | Patient received 1 mA of high-definition cathodal transcranial direct current for 5 minutes before endovascular procedure (EVT). Patient did not complete the pre-planned 20 minutes of stimulation due to the initiation of EVT. |
| FG001 | Sham Arm | Patients in the sham stimulation arm at all the tiers will have the cap and electrodes in place, and sham switch moved but without delivery of electrical stimulation. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Study was stopped early.
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| ID | Title | Description |
|---|---|---|
| BG000 | Active Stimulation Arm | Patient received 1 mA of high-definition cathodal transcranial direct current for 5 minutes before endovascular procedure (EVT). The pre-planned 20-min stimulation was not completed due to EVT initiation. |
| BG001 | Sham Arm |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Primary Safety Outcome- Number of Participants With Symptomatic Intracranial Hemorrhage (SICH) | Symptomatic intracranial hemorrhage (SICH) is defined as an increase of 4 or more points on the National Institute of Health Stroke Scale (NIHSS) total score within 24 hours of stimulation associated with parenchymal hematoma type 1 (PH1), parenchymal hematoma type 2 (PH2), remote intraparenchymal hemorrhage (RIH), subarachnoid hemorrhage (SAH), or intraventricular hemorrhage (IVH). The NIHSS is a 15-item neurologic examination stroke scale used to evaluate the effect of acute stroke on the levels of consciousness, language, neglect, visual-field loss, extraocular movement, motor strength, ataxia, dysarthria, and sensory loss. A trained observer rates the patent's ability to answer questions and perform activities. Ratings for each item are scored with 3 to 5 grades with 0 as normal, and there is an allowance for untestable items. Accordingly, 0 is the lowest and 42 is the highest total score possible. In the NIHSS, the higher the score, the more impaired a stroke patient is. | The study was stopped early after the enrollment of the first patient. | Posted | Count of Participants | Participants | At 24-hour post-stimulation |
90 days after enrollment
Study was stopped early, no sham was enrolled
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Active Stimulation Arm | Patient received 1 mA of high-definition cathodal transcranial direct current for 5 minutes before endovascular procedure (EVT). The pre-planned 20-min stimulation was not completed due to EVT initiation. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anticipated serious adverse events | Nervous system disorders | Systematic Assessment | Anticipated serious adverse events were defined as SAEs that are expected and related to acute ischemic stroke complications such as death related to family withdrawal of care (as in our patient), death due to malignant ischemic stroke, etc. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Mersedeh Bahr Hosseini | UCLA | 3107941195 | MBahrHosseini@mednet.ucla.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jan 12, 2021 | Mar 15, 2023 | Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | Apr 27, 2021 | Mar 15, 2023 | ICF_001.pdf |
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| ID | Term |
|---|---|
| D000083242 | Ischemic Stroke |
| ID | Term |
|---|---|
| D020521 | Stroke |
| D002561 | Cerebrovascular Disorders |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
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| ID | Term |
|---|---|
| D065908 | Transcranial Direct Current Stimulation |
| ID | Term |
|---|---|
| D004599 | Electric Stimulation Therapy |
| D013812 | Therapeutics |
| D003295 | Convulsive Therapy |
| D013000 | Psychiatric Somatic Therapies |
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Traditional 3+3 (rule-based, modified Fibonacci) dose-escalation design
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| At 24-hour post-stimulation |
| Secondary Safety Outcome-Number of Participants With Early Neurologic Deterioration | Worsening of total score ≥ 4 on NIHSS during the 24-hour period after stimulation, with or without intracranial hemorrhage. The NIHSS is a 15-item neurologic examination stroke scale used to evaluate the effect of acute stroke on the levels of consciousness, language, neglect, visual-field loss, extraocular movement, motor strength, ataxia, dysarthria, and sensory loss. A trained observer rates the patent's ability to answer questions and perform activities. Ratings for each item are scored with 3 to 5 grades with 0 as normal, and there is an allowance for untestable items. Accordingly, 0 is the lowest and 42 is the highest total score possible. In the NIHSS, the higher the score, the more impaired a stroke patient is. | At 24-hour post-stimulation |
| Secondary Safety Outcome-Number of Participants With Mortality | Rate of mortality | At 90 days post-stimulation |
| Secondary Safety Outcome-Number of Participants With All Serious Adverse Events (Anticipated and Unanticipated) | A serious adverse event (SAE) is any adverse event that is fatal, is life-threatening, is permanently or substantially disabling, requires or prolongs hospitalization, or requires medical or surgical intervention to prevent one of the above outcomes. Anticipated serious adverse events were defined as SAEs that are expected and related to acute ischemic stroke complications such as headache, stroke recurrence, pneumonia, systemic blood clots, Family withdrawal of care, etc. An unanticipated serious adverse event is an SAE that is not deemed an ischemic stroke complication and adjudicated as possibly related to study treatment. | At 90 days post-stimulation |
| Change in the penumbral volume between the timepoints: baseline, 2- hour, and 24-hour post-stimulation |
| Exploratory Clinical Efficacy Outcome- Assessing 3 Months Disability | Examining the clinical outcomes of 3-month modified Rankin Scale. The modified Rankin Scale 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 scale runs from 0-6, running from perfect health without symptoms to death. | At day-90 post stimulation |
Patients in the sham stimulation arm were planned to have the cap and electrodes in place but without delivery of electrical stimulation. No patient was enrolled in sham arm as the study was stopped early due to slow enrollment rate. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| ID | Title | Description |
|---|
| OG000 | Active Stimulation Arm | Patient received 1 mA of high-definition cathodal transcranial direct current for 5 minutes before endovascular procedure (EVT). The pre-planned 20-min stimulation was not completed due to EVT initiation. |
| OG001 | Sham Arm | Patients in the sham stimulation arm were planned to have the cap and electrodes in place, but without delivery of electrical stimulation. No patient was enrolled in the sham arm as the study was stopped early due to slow enrollment rate. |
|
|
| Primary | Primary Tolerability Outcome-Number of Participants Completing the Protocol-assigned Stimulation | The percentage of the patients completing the protocol-assigned stimulation treatment with no intolerability. | The study was stopped early after the enrollment of the first patient. | Posted | Count of Participants | Participants | After 5 minutes of stimulation period |
|
|
|
| Primary | Primary Feasibility Outcome- Assessing the Speed of Stimulation Implementation From Randomization. | The median times from randomization to bridging C-tDCS initiation and the time form end of endovascular thrombectomy procedure to adjunctive C-tDCS initiation in the last 10 enrolled patients. | Study was stopped early after enrollment of first patient. No patient was enrolled in sham arm. | Posted | Number | minutes | Median time from randomization to tDCS initiation |
|
|
|
| Secondary | Secondary Safety Outcome-Number of Participants With Asymptomatic Intracranial Hemorrhage (AICH) | AICH is defined as intracranial hemorrhage not associated with National Institute of Health Stroke Scale (NIHSS) total score worsening of ≥ 4. The NIHSS is a 15-item neurologic examination stroke scale used to evaluate the effect of acute stroke on the levels of consciousness, language, neglect, visual-field loss, extraocular movement, motor strength, ataxia, dysarthria, and sensory loss. A trained observer rates the patent's ability to answer questions and perform activities. Ratings for each item are scored with 3 to 5 grades with 0 as normal, and there is an allowance for untestable items. Accordingly, 0 is the lowest and 42 is the highest total score possible. In the NIHSS, the higher the score, the more impaired a stroke patient is. | One patient was enrolled in the Active arm and no patient in sham arm. | Posted | Number | participants | At 24-hour post-stimulation |
|
|
|
| Secondary | Secondary Safety Outcome-Number of Participants With Early Neurologic Deterioration | Worsening of total score ≥ 4 on NIHSS during the 24-hour period after stimulation, with or without intracranial hemorrhage. The NIHSS is a 15-item neurologic examination stroke scale used to evaluate the effect of acute stroke on the levels of consciousness, language, neglect, visual-field loss, extraocular movement, motor strength, ataxia, dysarthria, and sensory loss. A trained observer rates the patent's ability to answer questions and perform activities. Ratings for each item are scored with 3 to 5 grades with 0 as normal, and there is an allowance for untestable items. Accordingly, 0 is the lowest and 42 is the highest total score possible. In the NIHSS, the higher the score, the more impaired a stroke patient is. | One patient was enrolled in the Active arm and no patient in sham arm. | Posted | Count of Participants | Participants | At 24-hour post-stimulation |
|
|
|
| Secondary | Secondary Safety Outcome-Number of Participants With Mortality | Rate of mortality | One patient was enrolled in the Active arm and no patient in sham arm. | Posted | Count of Participants | Participants | At 90 days post-stimulation |
|
|
|
| Secondary | Secondary Safety Outcome-Number of Participants With All Serious Adverse Events (Anticipated and Unanticipated) | A serious adverse event (SAE) is any adverse event that is fatal, is life-threatening, is permanently or substantially disabling, requires or prolongs hospitalization, or requires medical or surgical intervention to prevent one of the above outcomes. Anticipated serious adverse events were defined as SAEs that are expected and related to acute ischemic stroke complications such as headache, stroke recurrence, pneumonia, systemic blood clots, Family withdrawal of care, etc. An unanticipated serious adverse event is an SAE that is not deemed an ischemic stroke complication and adjudicated as possibly related to study treatment. | One patient was enrolled in the Active arm and no patient in sham arm. | Posted | Count of Participants | Participants | At 90 days post-stimulation |
|
|
|
| Other Pre-specified | Exploratory Imaging Efficacy Outcome- Assessing Imaging Biomarker of Neuroprotection and Collateral Enhancement | By comparing the baseline MR/CT imaging with the MR/CT imaging at 2-hour (early) and 24-hour (final) post-stimulation, the following were planned to be measured: 1) Final penumbra salvage proportion, 2) Final hypoperfusion lesion reduction, 3) Early relative quantitative cerebral blood volume (qrCBV) enhancement. | One patient was enrolled in the Active arm and no patient in sham arm. Secondary outcome data were not collected in the one active patient. | Posted | Change in the penumbral volume between the timepoints: baseline, 2- hour, and 24-hour post-stimulation |
|
|
| Other Pre-specified | Exploratory Clinical Efficacy Outcome- Assessing 3 Months Disability | Examining the clinical outcomes of 3-month modified Rankin Scale. The modified Rankin Scale 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 scale runs from 0-6, running from perfect health without symptoms to death. | One patient was enrolled in the Active arm and no patient in sham arm. Secondary outcome data were not collected in the one active patient. | Posted | At day-90 post stimulation |
|
|
| 1 |
| 1 |
| 1 |
| 1 |
| 0 |
| 1 |
| EG001 | Sham Arm | Patients in the sham stimulation arm were planned to have the cap and electrodes in place, but without delivery of electrical stimulation. No patient was enrolled in sham arm as the study was stopped early due to slow enrollment rate. | 0 | 0 | 0 | 0 | 0 | 0 |
|
| Unanticipated serious adverse event | Nervous system disorders | Systematic Assessment | An unanticipated serious adverse event is an SAE that is not deemed an ischemic stroke complication and adjudicated as possibly related to study treatment |
|
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| D009422 |
| Nervous System Diseases |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D004191 | Behavioral Disciplines and Activities |
| D004597 | Electroshock |
| D011580 | Psychological Techniques |