Study on Hibernation-like Therapy Based on Mechanical Thrombectomy

Summary

The goal of this clinical trial is to learn whether chlorpromazine and promethazine（C+P）is safe in Acute Ischemic Stroke（AIS) patients and determine the maximum dosage. It will also evaluate the preliminary efficacy of C+P in AIS. The main questions it aims to answer are: What is the optimal dosage of C+P that is safe without causing adverse effects in AIS patients? What is the optimal dosage of C+P that potentially works to treat AIS? Researchers will compare C+P with placebo (saline solution without C+P) to see if C+P is safe and effective in treating Acute Ischemic Stroke. Participants will: Receive C+P or placebo at the same time as endovascular thrombectomy begins. Patients will be observed for 72 hours to see if there were any adverse effects related to C+P. Infarct volumes will be evaluated using Computed Tomography. Functional outcomes will be assessed at 90 days.

Timeline

Start

2024-11-09

Primary completion

2025-01

Completion

2025-02

Publications

• Background Tarahovsky YS, Fadeeva IS, Komelina NP, Khrenov MO, Zakharova NM. Antipsychotic inductors of brain hypothermia and torpor-like states: perspectives of application. Psychopharmacology (Berl). 2017 Jan;234(2):173-184. doi: 10.1007/s00213-016-4496-2. Epub 2016 Dec 8.
• Background Guan L, Guo S, Yip J, Elkin KB, Li F, Peng C, Geng X, Ding Y. Artificial Hibernation by Phenothiazines: A Potential Neuroprotective Therapy Against Cerebral Inflammation in Stroke. Curr Neurovasc Res. 2019;16(3):232-240. doi: 10.2174/1567202616666190624122727.
• Background Guo S, Cosky E, Li F, Guan L, Ji Y, Wei W, Peng C, Geng X, Ding Y. An inhibitory and beneficial effect of chlorpromazine and promethazine (C + P) on hyperglycolysis through HIF-1alpha regulation in ischemic stroke. Brain Res. 2021 Jul 15;1763:147463. doi: 10.1016/j.brainres.2021.147463. Epub 2021 Apr 1.
• Background Guo S, Li F, Wills M, Yip J, Wehbe A, Peng C, Geng X, Ding Y. Chlorpromazine and Promethazine (C+P) Reduce Brain Injury after Ischemic Stroke through the PKC-delta/NOX/MnSOD Pathway. Mediators Inflamm. 2022 Jul 15;2022:6886752. doi: 10.1155/2022/6886752. eCollection 2022.
• Background Tong Y, Elkin KB, Peng C, Shen J, Li F, Guan L, Ji Y, Wei W, Geng X, Ding Y. Reduced Apoptotic Injury by Phenothiazine in Ischemic Stroke through the NOX-Akt/PKC Pathway. Brain Sci. 2019 Dec 15;9(12):378. doi: 10.3390/brainsci9120378.
• Background Jiang Q, Wills M, Geng X, Ding Y. Chlorpromazine and promethazine reduces Brain injury through RIP1-RIP3 regulated activation of NLRP3 inflammasome following ischemic stroke. Neurol Res. 2021 Aug;43(8):668-676. doi: 10.1080/01616412.2021.1910904. Epub 2021 Apr 8.
• Background Han Y, Geng XK, Lee H, Li F, Ding Y. Neuroprotective Effects of Early Hypothermia Induced by Phenothiazines and DHC in Ischemic Stroke. Evid Based Complement Alternat Med. 2021 Jan 18;2021:1207092. doi: 10.1155/2021/1207092. eCollection 2021.
• Background Lv S, Zhao W, Rajah GB, Dandu C, Cai L, Cheng Z, Duan H, Dai Q, Geng X, Ding Y. Rapid Intervention of Chlorpromazine and Promethazine for Hibernation-Like Effect in Stroke: Rationale, Design, and Protocol for a Prospective Randomized Controlled Trial. Front Neurol. 2021 Mar 17;12:621476. doi: 10.3389/fneur.2021.621476. eCollection 2021.
• Background Seners P, Yuen N, Mlynash M, Snyder SJ, Heit JJ, Lansberg MG, Christensen S, Albucher JF, Cognard C, Sibon I, Obadia M, Savatovsky J, Baron JC, Olivot JM, Albers GW; Mismatch Prevalence Investigators. Quantification of Penumbral Volume in Association With Time From Stroke Onset in Acute Ischemic Stroke With Large Vessel Occlusion. JAMA Neurol. 2023 May 1;80(5):523-528. doi: 10.1001/jamaneurol.2023.0265.

Drugs

Indications