COOLing of the Ischemic PENumbra in Patients With Acute Ischemic Stroke.

NCT07844096 | Not Yet Recruiting DMC

• 1 other identifier: PEN-Cool
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 5

Brief Summary

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):

Conditions

Acute Ischemic Stroke

Keywords

Acute Ischemic Stroke; Selective brain cooling; Conductive cooling; PEN-Cool; Therapeutic hypothermia; Neuroprotection; Ischemic penumbra; Reperfusion therapy; Intravenous thrombolysis; Endovascular thrombectomy; Head and neck cooling

Outcome Measures

Primary Outcomes (1)

• 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.

  3 months

Secondary Outcomes (4)

• Interruption of cooling system

  3 months

• NIHSS

  24 hours

• mRS

  3 months

• Safety outcome

  3 months

Study Arms (2)

Selective Brain Cooling + Standard Reperfusion Therapy

EXPERIMENTAL

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

Standard Reperfusion Therapy / Routine Care

ACTIVE COMPARATOR

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

Interventions

PEN-Cool Conductive Head-and-Neck Cooling System DEVICE

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.

Selective Brain Cooling + Standard Reperfusion Therapy

Standard Reperfusion Therapy / Routine Care OTHER

Standard of care management for acute ischemic stroke according to institutional practice, including intravenous thrombolysis, endovascular thrombectomy, or both when indicated.

Standard Reperfusion Therapy / Routine Care

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• PHASE l
• Healthy adult participants of any gender aged 18 years or older and able to provide
• informed consent.
• PHASE II
• \. Adult patients of any gender, presenting with acute ischemic stroke and eligible for reperfusion therapy IVT or EVT or Both as per guidelines.

You may not qualify if:

• PHASE I
• History of uncontrolled hypertension or cardiovascular disease.
• Hematologic dyscrasias that can affect thrombosis like cryoglobulinemia or sickle cell disease or serum cold agglutinins.
• Vasospastic disorders like Raynaud or thromboangiitis obliteran.
• Skin lesions not allowing secure application of the cooling system
• PHASE II
• Surface Body temperature less than and equal to 35 degree Celcius at baseline
• Blood pressure more than or equal to 185 by 110 mmHg not responsive to guideline-directed intravenous antihypertensive therapy
• Known contraindications to hypothermia including hemodynamically unstable patients with new or symptomatic bradyarrhythmia known hematologic dyscrasias that affect thrombosis or vasospastic disorders such as Raynaud syndrome or thrombo angiitis obliterans.
• Skin lesions on scalp or neck preventing secure application of the cooling cap.
• Pre-morbid mRS more than or equal to 3
• Patients with known diseases or conditions resulting in an expected life expectancy of less than or equal to 3 months

Sponsors & Collaborators

• Christian Medical College and Hospital, Ludhiana, India: lead
• Indian Council of Medical Research: collaborator

Study Sites (5)

Amrita Institute of Medical Sciences- Kochi

Kochi, Kerala, 682041, India

Location

All India Institute of Medical Sciences- AIIMS

New Delhi, National Capital Territory of Delhi, 110029, India

Location

Christian Medical College and Hospital

Ludhiana, Punjab, 141008, India

Location

Christian Medical College and Hospital, Vellore

Vellore, Tamil Nadu, 632004, India

Location

Indian Institute of Technology, Kharagpur-IIT

Kharagpur, West Bengal, 721302, India

Location

Related Publications (5)

• Goyal M, Ospel JM, Ganesh A, Dowlatshahi D, Volders D, Mohlenbruch MA, Jumaa MA, Nimjee SM, Booth TC, Buck BH, Kennedy J, Shankar JJ, Dorn F, Zhang L, Hametner C, Nardai S, Zafar A, Diprose W, Vatanpour S, Stebner A, Bosshart S, Singh N, Sebastian I, Uchida K, Ryckborst KJ, Fahed R, Hu SX, Vollherbst DF, Zaidi SF, Lee VH, Lynch J, Rempel JL, Teal R, Trivedi A, Bode FJ, Ogungbemi A, Pham M, Orosz P, Abdalkader M, Taschner C, Tarpley J, Poli S, Singh RJ, De Leacy R, Lopez G, Sahlas D, Chen M, Burns P, Schaafsma JD, Marigold R, Reich A, Amole A, Field TS, Swartz RH, Settecase F, Lenzser G, Ortega-Gutierrez S, Asdaghi N, Lobotesis K, Siddiqui AH, Berrouschot J, Mokin M, Ebersole K, Schneider H, Yoo AJ, Mandzia J, Klostranec J, Jadun C, Patankar T, Sauvageau E, Lenthall R, Peeling L, Huynh T, Budzik R, Lee SK, Makalanda L, Levitt MR, Perry RJ, Hlaing T, Jahromi BS, Singh P, Demchuk AM, Hill MD; ESCAPE-MeVO Investigators. Endovascular Treatment of Stroke Due to Medium-Vessel Occlusion. N Engl J Med. 2025 Apr 10;392(14):1385-1395. doi: 10.1056/NEJMoa2411668. Epub 2025 Feb 5.

  PMID: 39908448 RESULT

• Pandian JD, Sylaja PN, Lackland DT, Babu V, Kumar Paramasivan N, Sebastian I, Parati G, Anderson CS, Ovbiagele B, Fisher M, Martins S, Whelton P. World Stroke Organization and World Hypertension League position statement on hypertension control strategies in prevention and management of stroke. Int J Stroke. 2025 Feb;20(2):151-165. doi: 10.1177/17474930241309276. Epub 2025 Jan 3.

  PMID: 39670456 RESULT

• Pandian JD, Kalkonde Y, Sebastian IA, Felix C, Urimubenshi G, Bosch J. Stroke systems of care in low-income and middle-income countries: challenges and opportunities. Lancet. 2020 Oct 31;396(10260):1443-1451. doi: 10.1016/S0140-6736(20)31374-X.

  PMID: 33129395 RESULT

• Sebastian IA, Gandhi DBC, Sylaja PN, Paudel R, Kalkonde YV, Yangchen Y, Gunasekara H, Injety RJ, Vijayanand PJ, Chawla NS, Oo S, Hla KM, Tenzin T, Pandian JD. Stroke systems of care in South-East Asia Region (SEAR): commonalities and diversities. Lancet Reg Health Southeast Asia. 2023 Oct 9;17:100289. doi: 10.1016/j.lansea.2023.100289. eCollection 2023 Oct.

  PMID: 37849930 RESULT

• Kalra LP, Khatter H, Ramanathan S, Sapehia S, Devi K, Kaliyaperumal A, Bal D, Sebastian I, Kakarla R, Singhania A, Rathore S, Klinsing S, Pandian JD, Foerch C. Serum GFAP for stroke diagnosis in regions with limited access to brain imaging (BE FAST India). Eur Stroke J. 2021 Jun;6(2):176-184. doi: 10.1177/23969873211010069. Epub 2021 May 11.

  PMID: 34414293 RESULT

MeSH Terms

Conditions

Ischemic Stroke

Condition Hierarchy (Ancestors)

Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Dr Jeyaraj D Pandian

  Christian Medical College and Hospital, Ludhiana, India

  PRINCIPAL INVESTIGATOR

• Dr ATUL PHILLIPS

  Christian Medical College and Hospital, Ludhiana, India

  PRINCIPAL INVESTIGATOR

• Dr Ivy A Sebastian

  Christian Medical College and Hospital, Ludhiana, India

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Dr Ivy A Sebastian

CONTACT

9999464986; ivy29cmc@gmail.com

Dr Jeyaraj D Pandian, MD DM

CONTACT

9915784750; ivy29cmc@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: This is an open-label randomized controlled trial. Participants, care providers, investigators, and outcome assessors will not be masked to treatment allocation.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: (Phase I) Prospective, single-arm, non-randomized, open-label feasibility and safety study. -Assess device tolerability, safety, and cooling efficacy in healthy volunteers (n=15) under controlled conditions, with continuous monitoring of physiological parameters (Phase III) Multicentre, parallel-group, pilot randomized controlled trial with 1:1 allocation to adjunctive non-invasive selective brain cooling plus standard reperfusion therapy or standard reperfusion therapy alone. Centralized web-based randomization will be used.

Study Record Dates

• First Submitted: August 26, 2026
• First Posted: September 28, 2026
• Study Start (Estimated): September 1, 2027
• Primary Completion (Estimated): August 30, 2031
• Study Completion (Estimated): August 30, 2031
• Last Updated: September 28, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will not share

Locations

IN (5)