Trial Outcomes & Findings for Transcranial Direct Current Stimulation as a Neuroprotection in Acute Stroke (NCT NCT03574038)

NCT ID: NCT03574038

Last Updated: 2023-06-27

Results Overview

The presence of SICH will be assessed on 24-hour post-stimulation scan. SICH will be defined as an intracranial parenchymal hemorrhage, subarachnoid hemorrhage, or intraventricular hemorrhage with an increase of 4 or more points on the National Institute of Health Stroke Scale (NIHSS) within 24 hours of stimulation.The treatment will be considered to have exhibited adequate safety if tDCS results in lower or equivalent rates of SICH compared to sham. The NIHSS is a validated quantitative assessment tool to measure stroke-related neurological deficits and ranges from 0 (no neurological deficits) to a maximum of 42, indicative of a very severe level of impairment.

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 10 participants
• Primary outcome timeframe: At 24-hour post-stimulation
• Results posted on: 2023-06-27

Participant Flow

The first 4 patients (3 Active and 1 Sham) were assigned to Tier 1 (1mA of C-tDCS for 20 min) of the study, and the next 6 patients (4 Active and 2 Sham) were assigned to Tier 2 (2mA of C-tDCS for 20 min) of the study.

Participant milestones

Measure	High-definition Cathodal Transcranial Direct Current Stimulation (HD C-tDCS)-Tier 1 The first 4 patients were randomized to 1mA of HD C-tDCS for 20 min vs. sham stimulation in a 3:1 ratio. A total of 3 patients received active stimulation.	High-definition Cathodal Transcranial Direct Current Stimulation (HD C-tDCS)-Tier 2 The next 6 patients were randomized to 2mA of HD C-tDCS for 20 min vs. sham stimulation in a 3:1 ratio. A total of 4 patients received active stimulation.	Sham Stimulation Sham Stimulation Sham Stimulation: A total of 3 patients were enrolled in the Sham arm at Tier 1 and 2. Patients in sham arm had the cap and electrodes in place but without any delivery of electrical stimulation.
Overall Study STARTED	3	4	3
Overall Study COMPLETED	3	4	3
Overall Study NOT COMPLETED	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Transcranial Direct Current Stimulation as a Neuroprotection in Acute Stroke

Baseline characteristics by cohort

Measure	High-definition Cathodal Transcranial Direct Current Stimulation n=7 Participants High-definition Cathodal Transcranial Direct Current Stimulation	Sham Stimulation n=3 Participants Sham Stimulation	Total n=10 Participants Total of all reporting groups
Age, Continuous	75 Year STANDARD_DEVIATION 19.6 • n=5 Participants	77 Year STANDARD_DEVIATION 12 • n=7 Participants	75 Year STANDARD_DEVIATION 9.6 • n=5 Participants
Sex: Female, Male Female	5 Participants n=5 Participants	1 Participants n=7 Participants	6 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	7 Participants n=5 Participants	2 Participants n=7 Participants	9 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: At 24-hour post-stimulation

Population: One SICH occurred in a Tir 2 patient due to a rupture of mycotic aneurysm causing subarachnoid hemorrhage. This misenrollment was later deemed to be a protocol deviation due to not meeting the entry criteria.

The presence of SICH will be assessed on 24-hour post-stimulation scan. SICH will be defined as an intracranial parenchymal hemorrhage, subarachnoid hemorrhage, or intraventricular hemorrhage with an increase of 4 or more points on the National Institute of Health Stroke Scale (NIHSS) within 24 hours of stimulation.The treatment will be considered to have exhibited adequate safety if tDCS results in lower or equivalent rates of SICH compared to sham.

The NIHSS is a validated quantitative assessment tool to measure stroke-related neurological deficits and ranges from 0 (no neurological deficits) to a maximum of 42, indicative of a very severe level of impairment.

Outcome measures

Measure	Active Stimulation-Tier 1 n=3 Participants High-definition Cathodal Transcranial Direct Current Stimulation (1mA-20min)	Active Stimulation-Tier 2 n=4 Participants High-definition Cathodal Transcranial Direct Current Stimulation (2mA-20min)	Sham Stimulation n=3 Participants Sham Stimulation Sham Stimulation: 3 patients were enrolled in the Sham arm: Patients had the cap and electrodes in place but without any delivery of electrical stimulation.
Safety Outcome: Rate of Symptomatic Intracranial Hemorrhage (SICH) in the Active Treatment Arms Compared to Sham Arm	0 Participants	1 Participants	0 Participants

PRIMARY outcome

Timeframe: Time from randomization to tDCS initiation assessed up to 30 minutes

Population: The time from enrollment to HD C-tDCS initiation in the last 4 enrolled patients.

The median time from enrollment to HD C-tDCS initiation in the last 4 enrolled patients included three Active-Tier 2 patients and one sham.

Outcome measures

Measure	Active Stimulation-Tier 1 n=4 Participants High-definition Cathodal Transcranial Direct Current Stimulation (1mA-20min)	Active Stimulation-Tier 2 High-definition Cathodal Transcranial Direct Current Stimulation (2mA-20min)	Sham Stimulation Sham Stimulation Sham Stimulation: 3 patients were enrolled in the Sham arm: Patients had the cap and electrodes in place but without any delivery of electrical stimulation.
Feasibility Outcome: Speed With Which HD C-tDCS Was Implemented	12.5 minutes Interval 9.0 to 15.0	—	—

PRIMARY outcome

Timeframe: After 20 minutes of stimulation period

Population: Rate of patients completing the protocol assigned stimulation

Percentage of the patients completing the protocol-assigned stimulation treatment

Outcome measures

Measure	Active Stimulation-Tier 1 n=3 Participants High-definition Cathodal Transcranial Direct Current Stimulation (1mA-20min)	Active Stimulation-Tier 2 n=4 Participants High-definition Cathodal Transcranial Direct Current Stimulation (2mA-20min)	Sham Stimulation n=3 Participants Sham Stimulation Sham Stimulation: 3 patients were enrolled in the Sham arm: Patients had the cap and electrodes in place but without any delivery of electrical stimulation.
Tolerability Outcome: Percentage of the Patients Completing the Protocol-assigned Stimulation Treatment	3 Participants	4 Participants	3 Participants

SECONDARY outcome

Timeframe: During the 24-hour post-stimulation

Early neurological deterioration will be defined as worsening ≥ 4 on NIHSS during the 24-hour period after stimulation without intracranial hemorrhage.

Outcome measures

Measure	Active Stimulation-Tier 1 n=7 Participants High-definition Cathodal Transcranial Direct Current Stimulation (1mA-20min)	Active Stimulation-Tier 2 n=3 Participants High-definition Cathodal Transcranial Direct Current Stimulation (2mA-20min)	Sham Stimulation Sham Stimulation Sham Stimulation: 3 patients were enrolled in the Sham arm: Patients had the cap and electrodes in place but without any delivery of electrical stimulation.
Secondary Safety Outcome: Rate of Early Neurologic Deterioration in All Active Patients Compared to Sham Arm	1 Participants	0 Participants	—

SECONDARY outcome

Timeframe: By day 90 post stimulation

Mortality will be defined as death or modified Rankin Scale of 6.

Outcome measures

Measure	Active Stimulation-Tier 1 n=7 Participants High-definition Cathodal Transcranial Direct Current Stimulation (1mA-20min)	Active Stimulation-Tier 2 n=3 Participants High-definition Cathodal Transcranial Direct Current Stimulation (2mA-20min)	Sham Stimulation Sham Stimulation Sham Stimulation: 3 patients were enrolled in the Sham arm: Patients had the cap and electrodes in place but without any delivery of electrical stimulation.
Secondary Safety Outcome: Rate of Mortality in All Active Patients Compared to Sham Arm,	2 Participants	1 Participants	—

SECONDARY outcome

Timeframe: By day 90 post-stimulation

A serious adverse event 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. The rate of serious adverse events will be compared between the active treatment and sham patients.

Outcome measures

Measure	Active Stimulation-Tier 1 n=7 Participants High-definition Cathodal Transcranial Direct Current Stimulation (1mA-20min)	Active Stimulation-Tier 2 n=3 Participants High-definition Cathodal Transcranial Direct Current Stimulation (2mA-20min)	Sham Stimulation Sham Stimulation Sham Stimulation: 3 patients were enrolled in the Sham arm: Patients had the cap and electrodes in place but without any delivery of electrical stimulation.
Secondary Safety Outcome: Rate of All Serious Adverse Events Occured During the 90 Days of Study Participation in All Active Patients Compared to Sham.	3 Participants	2 Participants	—

OTHER_PRE_SPECIFIED outcome

Timeframe: At 2-hour and 24-hour post-stimulation

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 measured: 1) Final penumbra salvage proportion, 2) Final hypoperfusion lesion reduction, 3) Early relative quantitative cerebral blood volume (qrCBV) enhancement.

Outcome measures

Measure	Active Stimulation-Tier 1 n=5 Participants High-definition Cathodal Transcranial Direct Current Stimulation (1mA-20min)	Active Stimulation-Tier 2 n=3 Participants High-definition Cathodal Transcranial Direct Current Stimulation (2mA-20min)	Sham Stimulation Sham Stimulation Sham Stimulation: 3 patients were enrolled in the Sham arm: Patients had the cap and electrodes in place but without any delivery of electrical stimulation.
Per-protocol Exploratory Imaging Efficacy Outcome of Imaging Biomarkers of Neuroprotection and Collateral Enhancement Excluding One Patient With no Penumbra at Baseline on Imaging Core Review and One Patient With Septic Embolization as Stroke Cause. Final hypoperfusion lesion proportion percentage change	-100 percentage change from baseline Interval -100.0 to -46.0	325 percentage change from baseline Interval 112.0 to 412.0	—
Per-protocol Exploratory Imaging Efficacy Outcome of Imaging Biomarkers of Neuroprotection and Collateral Enhancement Excluding One Patient With no Penumbra at Baseline on Imaging Core Review and One Patient With Septic Embolization as Stroke Cause. Early qrCBV percentage change	64 percentage change from baseline Interval 40.0 to 110.0	-4 percentage change from baseline Interval -7.0 to 1.0	—
Per-protocol Exploratory Imaging Efficacy Outcome of Imaging Biomarkers of Neuroprotection and Collateral Enhancement Excluding One Patient With no Penumbra at Baseline on Imaging Core Review and One Patient With Septic Embolization as Stroke Cause. Final penumbra salvage proportion percentage	66 percentage change from baseline Interval 29.0 to 80.5	0 percentage change from baseline Interval 0.0 to 0.0	—

OTHER_PRE_SPECIFIED outcome

Timeframe: At day 90 post stimulation

Rate of modified Rankin Scale (mRS) of 0-2

Outcome measures

Measure	Active Stimulation-Tier 1 n=5 Participants High-definition Cathodal Transcranial Direct Current Stimulation (1mA-20min)	Active Stimulation-Tier 2 n=3 Participants High-definition Cathodal Transcranial Direct Current Stimulation (2mA-20min)	Sham Stimulation Sham Stimulation Sham Stimulation: 3 patients were enrolled in the Sham arm: Patients had the cap and electrodes in place but without any delivery of electrical stimulation.
Per-protocol Exploratory Clinical Efficacy Outcome: Rate of Functional Independence at 3-month in Active vs. Sham Excluding Two Patients, One With no Penumbra Was Present at Baseline on Imaging Core Review and One With Septic Embolization as Stroke Cause.	3 Participants	2 Participants	—

Adverse Events

Active Stimulation-Tier 1

Serious events: 1 serious events

Other events: 1 other events

Deaths: 0 deaths

Active Stimulation-Tier 2

Serious events: 2 serious events

Other events: 0 other events

Deaths: 2 deaths

Sham Stimulation

Serious events: 2 serious events

Other events: 0 other events

Deaths: 1 deaths

Serious adverse events

Measure	Active Stimulation-Tier 1 n=3 participants at risk High-definition Cathodal Transcranial Direct Current Stimulation 1mA-20min	Active Stimulation-Tier 2 n=4 participants at risk High-definition Cathodal Transcranial Direct Current Stimulation 2mA-20min	Sham Stimulation n=3 participants at risk Sham Stimulation Patients in sham arm had the cap and electrodes in place but without any delivery of electrical stimulation.
Nervous system disorders Anticipated serious adverse events	33.3% 1/3 • Number of events 1 • Three months following the study enrollment	50.0% 2/4 • Number of events 2 • Three months following the study enrollment	66.7% 2/3 • Number of events 2 • Three months following the study enrollment
Nervous system disorders Unanticipated serious adverse event	0.00% 0/3 • Three months following the study enrollment	0.00% 0/4 • Three months following the study enrollment	0.00% 0/3 • Three months following the study enrollment

Other adverse events

Measure	Active Stimulation-Tier 1 n=3 participants at risk High-definition Cathodal Transcranial Direct Current Stimulation 1mA-20min	Active Stimulation-Tier 2 n=4 participants at risk High-definition Cathodal Transcranial Direct Current Stimulation 2mA-20min	Sham Stimulation n=3 participants at risk Sham Stimulation Patients in sham arm had the cap and electrodes in place but without any delivery of electrical stimulation.
Nervous system disorders Anticipated AE	33.3% 1/3 • Number of events 1 • Three months following the study enrollment	0.00% 0/4 • Three months following the study enrollment	0.00% 0/3 • Three months following the study enrollment
Nervous system disorders Unanticipated adverse event	0.00% 0/3 • Three months following the study enrollment	0.00% 0/4 • Three months following the study enrollment	0.00% 0/3 • Three months following the study enrollment

Additional Information

Dr. Mersedeh Bahr-Hosseini

Study's principal investigator

Phone: 3107941195

Email: MBahrHosseini@mednet.ucla.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place