An interventional study of PEN-Cool Conductive Head-and-Neck Cooling System and Standard Reperfusion Therapy / Routine Care in Acute Ischemic Stroke, sponsored by Christian Medical College and Hospital, Ludhiana, India. Not yet recruiting at 5 sites in India. Open to participants aged 18 Years to 99 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-09-28.
Sponsored by Christian Medical College and Hospital, Ludhiana, India · Not applicable, Interventional, and Treatment
This study will develop and validate a novel, active/conductive combined head and neck cooling system to selectively cool the ischemic penumbra during the acute phase of stroke, reducing neuronal damage and improving stroke outcomes. It complements existing reperfusion therapies offering a scalable neuroprotective option which will have wider implications across diverse healthcare settings.
PHASE I: Technology Development \& Test Bench Optimization (Years 1-2) PHASE II: Validation in healthy volunteers (Year 3)
PHASE III: Pilot, multicenter, randomized controlled (Phase 2a) trial (Year 4-5):
PEN-Cool is a pilot, multicentre, randomized controlled trial evaluating a novel non-invasive active conductive combined head-and-neck cooling system for selective brain cooling in adults with acute ischemic stroke receiving reperfusion therapy. The study is part of a phased translational research programme involving technology development, validation in healthy volunteers, and clinical evaluation in patients with acute ischemic stroke.
The clinical trial will enroll 40 adult patients with acute ischemic stroke who are eligible for intravenous thrombolysis, endovascular thrombectomy, or both. Participants will be centrally randomized in a 1:1 ratio to either adjunctive selective brain cooling plus standard reperfusion therapy or standard reperfusion therapy alone.
In the intervention group, the conductive cooling system will be applied to the scalp and anterolateral and posterolateral neck. Cooling will begin before intravenous thrombolysis and/or endovascular thrombectomy in the emergency department or angiography suite and will continue for up to 120 minutes. The cooling interface will deliver temperatures ranging from -5°C to 0°C. Brain temperature will be monitored non-invasively using infrared tympanic membrane thermometry, while core body temperature will be monitored using a rectal or esophageal probe. Blood pressure, heart rate, and oxygen saturation will also be monitored.
Cooling will be discontinued if predefined safety or tolerability criteria are met, including intolerance, persistent cold-related shivering despite passive warming, core body temperature of 35°C or below, uncontrolled hypertension, symptomatic bradycardia or other unexpected medical events, or procedural complications.
The primary feasibility outcome is adherence to the cooling intervention, defined as receiving head cooling for at least 60% of the intended total cooling duration. Secondary feasibility outcomes include interruptions in cooling and monthly enrollment rate. Efficacy outcomes include early neurological improvement, defined as a 30% or greater improvement in NIHSS score at 24 hours, and good functional outcome, defined as a modified Rankin Scale score of 0-2 at 3 months. Safety outcomes include symptomatic bradyarrhythmia, uncontrolled hypertension, cold-related shivering, cervical or cerebral vasospasm requiring intra-arterial vasodilators, symptomatic intracranial hemorrhage, pneumonia, and mortality through 3 months. Process outcomes include time from hospital arrival to initiation of cooling and time from arrival to reperfusion therapy.
The study will assess whether selective brain cooling can be safely and feasibly integrated into acute ischemic stroke care without delaying established reperfusion workflows and will generate preliminary safety, feasibility, and efficacy data to inform a future adequately powered multicentre randomized controlled trial.
PHASE l
PHASE II
1. Adult patients of any gender, presenting with acute ischemic stroke and eligible for reperfusion therapy IVT or EVT or Both as per guidelines.
Exclusion Criteria:
PHASE I
PHASE II
Participants will receive adjunctive non-invasive selective brain cooling using the novel active conductive combined head-and-neck cooling system in addition to standard reperfusion therapy (intravenous thrombolysis, endovascular thrombectomy, or both).
Device: PEN-Cool Conductive Head-and-Neck Cooling System
Participants will receive standard of care management for acute ischemic stroke according to institutional practice, including indicated intravenous thrombolysis and/or endovascular thrombectomy, without selective brain cooling.
Other: Standard Reperfusion Therapy / Routine Care
A novel non-invasive active conductive combined head-and-neck cooling system designed to induce selective brain cooling while avoiding systemic hypothermia.Cooling will begin before IVT and/or EVT in the emergency department or angiography suite and continue for up to 120 minutes. The cooling system will contact the scalp and anterolateral and posterolateral neck and deliver temperatures ranging from -5°C to 0°C. Brain and core temperatures and physiological parameters will be monitored throughout the cooling period along with standard reperfusion.
Standard of care management for acute ischemic stroke according to institutional practice, including intravenous thrombolysis, endovascular thrombectomy, or both when indicated.
Adherence to the intervention cooling system.
Phase III (Feasibility outcomes) Primary feasibility outcome defined as the proportion of participants who will be adherent to the intervention. Adherence defined as undergoing head cooling for more than equal to 60 percent of the total time from the first application of the head and neck cooling system.
Time frame: 3 months
Interruption of cooling system
PHASE III Secondary feasibility outcomes include interruption of cooling and the monthly enrollment rate. High recrutements are good outcome.
Time frame: 3 months
NIHSS
Phase III Efficacy outcomes: Early neurological improvement, defined as a 30% or greater improvement in the NIHSS score at 24 h. Lower NIHSS is good outcome
Time frame: 24 hours
mRS
Phase III Good functional outcome at 3 months Good functional outcome, defined as an mRS of 0, 1, or 2, at 3 months assessed by telephone interview conducted by a trained researcher. Lower mRS indicates good outcome.
Time frame: 3 months
Safety outcome
Phase III Including bradyarrhythmia, pneumonia, shivering and cerebral vasospasm at 3 months.
Time frame: 3 months
Plan to share: No — Individual participant data will not be shared with external researchers.
This study is not yet recruiting, as verified in Sep 2026. You cannot join it, but the record below documents what was studied.
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Christian Medical College and Hospital, Ludhiana, India