Safety and Preliminary Efficacy of Hibernation-Like Therapy (Chlorpromazine and Promethazine) in Patients With Acute Ischemic Stroke (AIS) Eligible for Reperfusion Therapy.

NCT07364344 | Not Yet Recruiting DMC

• 3 other identifiers: CHILL-S3500-123203IIT-2025-YW055-02
• Study Type: interventional
• Target: 57
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a single-center, dose-escalation and dose-expansion Phase I study designed to evaluate the safety of hibernation-like therapy (Chlorpromazine and Promethazine, C+P) and observe improvements in infarct volume in patients with AIS eligible for reperfusion therapy.

Conditions

Acute Ischemic Stroke

Outcome Measures

Primary Outcomes (1)

• Observation of DLT and MTD across different C+P dose cohorts to determine the RP2D.

  From the initiation of Hibernation-Like Therapy until 7 days after treatment.

Secondary Outcomes (3)

• Change in cerebral infarct volume (mL) at 48 ±12 hours post-treatment compared to pre-treatment.

  From the start of Hibernation-Like Therapy to 48±12 hours after treatment.

• Change in the National Institutes of Health Stroke Scale (NIHSS) score at 24 hours post-treatment compared to baseline.

  From the start of Hibernation-Like Therapy to 24 hours after treatment.

• Magnitude of vital sign changes (absolute differences in temperature, BP, and respiration post-C+P vs. baseline).

  From the initiation of Hibernation-Like Therapy until 7 days after treatment.

Other Outcomes (1)

• Ratio of specific metabolite downregulation after 3 hours of C+P therapy versus baseline (serum enrichment analysis).

  From the start of Hibernation-Like Therapy to 3 hours after treatment.

Study Arms (1)

Hibernation-Like Therapy (Chlorpromazine and Promethazine)

EXPERIMENTAL

Drug: Hibernation-like Therapy (Chlorpromazine and Promethazine, C+P)

Interventions

Hibernation-like Therapy (Chlorpromazine and Promethazine, C+P) DRUG

The escalating doses are Chlorpromazine and Promethazine (C+P) at the following combinations: 50mg+50mg, 62.5mg+62.5mg, 75mg+75mg, and 100mg+100mg.Dose escalation will follow the "3+3" rule. Based on the dose-escalation results, dose expansion will be initiated at an appropriate time. The dose-expansion phase will consist of three cohorts: two cohorts receiving C+P and one cohort receiving an intravenous infusion of 50ml normal saline at room temperature (infusion rate also 50ml/h) prior to endovascular treatment. The two C+P dose groups for expansion will be selected based on the dose-escalation results. Patients will receive the study drug followed by reperfusion therapy. The administration method is the same as in the dose-escalation phase.

Hibernation-Like Therapy (Chlorpromazine and Promethazine)

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The subject or their legal guardian voluntarily agrees to participate by providing written informed consent, and agrees to comply with the trial treatment plan and visit schedule.
• Male or female, aged 18 to 80 years (inclusive).
• Diagnosis of acute ischemic stroke eligible for endovascular therapy.
• Clinical signs and symptoms consistent with acute anterior circulation ischemic stroke, with a National Institutes of Health Stroke Scale (NIHSS) score between 6 and 20 (inclusive).
• Note: The NIHSS score ranges from 0 to 42, with higher scores indicating more severe neurological deficits. Classification:
• \*0-1: Normal or near-normal.\*
• \*1-4: Minor stroke.\*
• \*5-15: Moderate stroke.\*
• \*15-20: Moderate to severe stroke.\*
• \*21-42: Severe stroke.\*
• Time from stroke onset to planned drug administration is within 24 hours.
• Pre-stroke modified Rankin Scale (mRS) score of 0 or 1.
• Expected survival greater than 90 days.
• Pre-procedural angiographic evaluation (NCCT + CTA + CTP / DSA) confirms a large vessel occlusion (internal carotid artery or M1 segment of middle cerebral artery) consistent with clinical symptoms.
• Alberta Stroke Program Early CT Score (ASPECTS) ≥ 6.

You may not qualify if:

• Presence of pathological fever at screening: axillary temperature ≥ 37.3°C or tympanic membrane temperature ≥ 37.9°C.
• Clinical presentation suggestive of intracranial parenchymal hemorrhage or subarachnoid hemorrhage (even with normal imaging findings).
• Stroke onset accompanied by seizures at screening, precluding accurate NIHSS assessment.
• Coma or psychiatric disorders at screening that interfere with neurological evaluation.
• Conditions contraindicating phenothiazine use at screening, such as Parkinson's disease, parkinsonism, basal ganglia disorders, bone marrow suppression, glaucoma, epilepsy, history of neuroleptic malignant syndrome, or history of hypersensitivity to phenothiazines.
• History of allergy or anaphylactic shock to iodinated contrast agents.
• Major surgery within 4 weeks prior to drug administration.
• Blood glucose \<50 mg/dL (2.78 mmol/L) or \>400 mg/dL (22.20 mmol/L) prior to drug administration (fingerstick glucose results acceptable).
• History of deep vein thrombosis within 6 months prior to drug administration.
• Previous endovascular thrombectomy performed less than 3 months prior.
• Clinically significant active bleeding (e.g., gastrointestinal or other) within 30 days prior to drug administration; coagulation factor abnormalities or bleeding tendency (e.g., on anticoagulants with INR ≥3 or PT ≥3×ULN). However, subjects may be enrolled without awaiting coagulation results if the investigator deems no coagulation dysfunction. Active infection requiring systemic therapy within 2 weeks prior to drug administration (e.g., active tuberculosis).
• Clinically significant cardiac disease at screening, including but not limited to:
• Uncontrolled hypertension (SBP \>180 mmHg or DBP \>105 mmHg after standard treatment) or hypotension (SBP ≤100 mmHg after standard treatment).
• Unstable angina, myocardial infarction, or coronary artery bypass graft/stent placement within 6 months prior to drug administration.
• History of chronic heart failure (NYHA Class 3-4), or valvular heart disease, deemed ineligible by the investigator.

Sponsors & Collaborators

• Ji Xunming,MD,PhD: lead

Related Publications (10)

• Baron JC. Protecting the ischaemic penumbra as an adjunct to thrombectomy for acute stroke. Nat Rev Neurol. 2018 Jun;14(6):325-337. doi: 10.1038/s41582-018-0002-2.

  PMID: 29674752 RESULT

• Al-Mufti F, Amuluru K, Roth W, Nuoman R, El-Ghanem M, Meyers PM. Cerebral Ischemic Reperfusion Injury Following Recanalization of Large Vessel Occlusions. Neurosurgery. 2018 Jun 1;82(6):781-789. doi: 10.1093/neuros/nyx341.

  PMID: 28973661 RESULT

• Fisher M, Saver JL. Future directions of acute ischaemic stroke therapy. Lancet Neurol. 2015 Jul;14(7):758-67. doi: 10.1016/S1474-4422(15)00054-X.

  PMID: 26067128 RESULT

• Andrews BJ, Herskowitz I. The yeast SWI4 protein contains a motif present in developmental regulators and is part of a complex involved in cell-cycle-dependent transcription. Nature. 1989 Dec 14;342(6251):830-3. doi: 10.1038/342830a0.

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• Nogueira RG, Jadhav AP, Haussen DC, Bonafe A, Budzik RF, Bhuva P, Yavagal DR, Ribo M, Cognard C, Hanel RA, Sila CA, Hassan AE, Millan M, Levy EI, Mitchell P, Chen M, English JD, Shah QA, Silver FL, Pereira VM, Mehta BP, Baxter BW, Abraham MG, Cardona P, Veznedaroglu E, Hellinger FR, Feng L, Kirmani JF, Lopes DK, Jankowitz BT, Frankel MR, Costalat V, Vora NA, Yoo AJ, Malik AM, Furlan AJ, Rubiera M, Aghaebrahim A, Olivot JM, Tekle WG, Shields R, Graves T, Lewis RJ, Smith WS, Liebeskind DS, Saver JL, Jovin TG; DAWN Trial Investigators. Thrombectomy 6 to 24 Hours after Stroke with a Mismatch between Deficit and Infarct. N Engl J Med. 2018 Jan 4;378(1):11-21. doi: 10.1056/NEJMoa1706442. Epub 2017 Nov 11.

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• Seners P, Turc G, Maier B, Mas JL, Oppenheim C, Baron JC. Incidence and Predictors of Early Recanalization After Intravenous Thrombolysis: A Systematic Review and Meta-Analysis. Stroke. 2016 Sep;47(9):2409-12. doi: 10.1161/STROKEAHA.116.014181. Epub 2016 Jul 26.

  PMID: 27462117 RESULT

• Tilley BC, Lyden PD, Brott TG, Lu M, Levine SR, Welch KM. Total quality improvement method for reduction of delays between emergency department admission and treatment of acute ischemic stroke. The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. Arch Neurol. 1997 Dec;54(12):1466-74. doi: 10.1001/archneur.1997.00550240020008.

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  PMID: 28919116 RESULT

MeSH Terms

Conditions

Ischemic Stroke

Interventions

Chlorpromazine; Promethazine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Phenothiazines; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Propylamines; Amines

Central Study Contacts

琦 王, Doctor

CONTACT

+86 15910461567; bingdianhedk@yeah.net

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Neurology, Xuanwu Hospital, Capital Medical University

Study Record Dates

• First Submitted: January 4, 2026
• First Posted: January 23, 2026
• Study Start: January 1, 2026
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2026
• Last Updated: January 23, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share