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Acute Ischemic StrokePhase 1CHILL-1NCT06663631

Study on Hibernation-like Therapy Based on Mechanical Thrombectomy

A Phase 1 study testing chlorpromazine and promethazine, endovascular thrombectomy and rt-PA in people with Acute Ischemic Stroke, run by Capital Medical University at 1 site in China.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 80 years
Conditions the study is for
Acute Ischemic Stroke
What is being tested?
chlorpromazine and promethazine, endovascular thrombectomy and rt-PA
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
32 participants
Where
1 siteChina
Study dates
9 Nov 2024to Feb 2025
Phase
Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Clinical Inclusion Criteria:
  • Age between 18-80 years(including the critical value)
  • Ischemic stroke with a National Institutes of Health Stroke Scale (NIHSS) score ranging from 6-20
  • Time from last known to be well to randomization within 24h
  • Pre-stroke Modified Rankin Scale scoring 0-1.
  • With indications of reperfusion therapy (including intravenous thrombolysis and endovascular thrombectomy).
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  • Informed consent signed by patients or their legal relatives.
  • CT angiography (CTA) confirmed large vessel occlusion of anterior circulation
  • Alberta Stroke Program Early Computed Tomography Score (ASPECT) score of 6-10.
  • initial infarct volume on CT perfusion (CTP) lesser than 70ml; a ratio of hypoperfused volume to infarcted volume greater than 1.8; absolute mismatch volume greater than 15 ml according to DEFUSE-3 trial.

Who cannot join

  • Clinical Exclusion Criteria:
  • Clinical findings suggest intracranial parenchymal hemorrhage or subarachnoid hemorrhage.
  • Accompanied by epilepsy.
  • Accompanied by coma or mental disorders, may interfere with neurological function assessment.
  • History of premorbid phenothiazine allergy or contraindication.
  • History of allergy to iodine contrast medium or anaphylactic shock
Show all 26Show fewer
  • Baseline blood glucose <50mg/dL (2.78mmol) or >400mg/dL (22.20mmol)
  • Acceptable fingertip blood glucose results
  • Baseline platelet <50×109 /L
  • Recent (i.e. within 30 days prior to randomization) history of gastrointestinal or other clinically significant bleeding; Active bleeding, abnormal clotting factors, or bleeding tendency (INR≥3 or PT≥3×ULN on anticoagulants; If the investigator believes that the subject does not have coagulation dysfunction, it is not necessary to wait for the results of the coagulation test before deciding whether to enroll.)
  • The stroke is accompanied by fever, or there is an active infection requiring systemic treatment (such as active tuberculosis, etc.)
  • Expected survival less than 90 days (According to the Chinese Guidelines for Early Endovascular Interventional Diagnosis and Treatment of Acute Ischemic Stroke 2022, expected survival less than 90 days is a contraindication for endovascular therapy)
  • A history of severe cardiovascular disease, including but not limited to: uncontrolled hypertension (systolic blood pressure >180 mmHg or diastolic blood pressure >105 mmHg after standard treatment), hypotension (systolic blood pressure ≤100 mmHg after standard treatment), or pulmonary hypertension; Had unstable angina pectoris, myocardial infarction, or bypass or stent surgery within 6 months before randomization; New York Heart Association (NYHA) grade 3-4 history of chronic heart failure; Clinically significant valvular disease; Severe arrhythmias requiring treatment (except atrial fibrillation and paroxysmal supraventricular tachycardia), including QT interval ≥450ms for men and ≥470ms for women
  • accompanied by chronic obstructive pulmonary disease（COPD）, tuberculosis, pneumonia, pneumothorax, atelectasis, pulmonary fibrosis, bronchopulmonary dysplasia, pleural effusion, acute respiratory distress syndrome, respiratory irregularity and other lung diseases
  • Severe hepatic and renal insufficiency, including but not limited to: cirrhosis, hepatic encephalopathy, ascites, renal failure or uremia (Ccr<25ml/min), hepatorenal syndrome, etc
  • Pregnancy or lactating women
  • Participation in other clinical trials and have used an investigational drug or medical device
  • Patients that may not be able to complete the study for other reasons or who the investigator believes should not be included
  • Image exclusion criteria:
  • computed tomographic angiography（CTA）/magnetic resonance angiography（MRA）/digital substraction angiography（DSA） shows excessive vascular curvature, which may hinder delivery of interventional devices
  • Cerebrovascular inflammation is suspected based on medical history and CTA/MRA/DSA
  • Aortic dissection is suspected based on medical history and CTA/MRA/DSA
  • CTA/MRA/DSA confirmed multi-vascular regional occlusion (such as bilateral anterior circulation or anterior/posterior circulation, extracranial carotid artery with intracranial tandem lesions), or clinical evidence of bilateral or multi-regional infarction
  • CTA/MRA/DSA confirms moyamoya disease or moyamoya syndrome
  • CT/MRI confirmed a significant midline shift effect
  • CT/MRI confirms the presence of intracranial tumors (except cerebellar meningioma) CT/MRI confirmed intracranial hemorrhage

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Xunming Ji, Doctor contact

+86 13911077166

Jixm@ccmu.edu.cn

Hao Wang, Doctor contact

+86 13518690201

neurology_hao@163.com

China1 site, 1 recruiting

  • Linyi People's Hospital

    Linyi, Shandong, 276000

    Qi Wang, Dr., +8615910461567, bingdianhedk@yeah.net

    Recruiting

Other trials in China

About this study

Official title: The Safety and effiCacy of HIbernation-Like Therapy Combining recanaLization in Ischemic Stroke: a Phase 1, Dose-escalation Study

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.

Read more

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.

Read the detailed description

Chlorpromazine and promethazine (C+P), due to their effort to induce a hibernation-like status, has been proved to be neuroprotective for ischemic stroke in pre-clinical experiments. However, whether it is safe and potentially effective in acute ischemic stroke (AIS) patients is currently unknown. The reason might be that the optimal dosage is not defined in AIS treatment. High dosage of C+P might result in hypotension and extrapyramidal symptoms that diminishes its neuroprotective effect. So it is essential to determine a safe and potentially dosage. Another reason might be that patients from previous clinical trials assessing the effectiveness of C+P did not receive reperfusion therapy. In this study，we plan to conduct a 6+2 dose-escalation clinical trial to determine the safety of C+P in AIS patients receiving endovascular thrombectomy. Four dosage groups of C+P will be set(10mg/20mg/50mg/100mg).A minimum of 32 patients will be involved if no drug related severe adverse event(SAE) was observed. A maximum of 64 patients will be required if one SAE is observed in each group. The current study aim to provide a basis for phase Ⅱ clinical trial to further explore the efficacy of C+P in AIS treatmment.

Being tested
chlorpromazine and promethazine, Placebo group, endovascular thrombectomy, rt-PA
Keywords
Hibernation-like status, Reperfusion, Neuroprotection, phenothiazine, dose-escalation
Medical subject headings
Ischemic Stroke

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • chlorpromazine and promethazineDrug

    Also called C+P, lytic cocktail

    C+P were diluted to 50 ml saline solution and delivered intravenously at the beginning of endovascular thrombectomyat a velocity of 4ml/h. The whole period of drug delivery lasts for approximately 12h.

  • Placebo groupDrug

    Also called Control group

    50 ml saline solution was set as placebo and delivered intravenously at the beginning of endovascular thrombectomyat a velocity of 4ml/h. The whole period of drug delivery lasts for approximately 12h.

  • endovascular thrombectomyProcedure or surgery

    All patients that are eligible for endovascular thrombectomy will receive this surgery in aim to remove thrombus and restore reperfusion.

  • rt-PADrug

    Also called Intravenous thrombolysis

    All patients that are eligible for Intravenous thrombolysis will receive 0.9mg/kg rt-PA in aim to remove thrombus and restore reperfusion

Study groups in NCT06663631
Study groupRoleWhat they receive
chlorpromazine and promethazine of Very low dosageExperimentalpatients will receive C+P（chlorpromazine and promethazine ,10 mg each)at the beginning of endovascular thrombectomy.
Receives: Drug: chlorpromazine and promethazine; Procedure: endovascular thrombectomy; Drug: rt-PA
chlorpromazine and promethazine of low-dosageExperimentalpatients will receive C+P（chlorpromazine and promethazine ,20 mg each)at the beginning of endovascular thrombectomy.
Receives: Drug: chlorpromazine and promethazine; Procedure: endovascular thrombectomy; Drug: rt-PA
chlorpromazine and promethazine of moderate dosageExperimentalpatients will receive C+P（chlorpromazine and promethazine ,50 mg each)at the beginning of endovascular thrombectomy.
Receives: Drug: chlorpromazine and promethazine; Procedure: endovascular thrombectomy; Drug: rt-PA
chlorpromazine and promethazine of high dosageExperimentalpatients will receive C+P（chlorpromazine and promethazine ,100 mg each)at the beginning of endovascular thrombectomy.
Receives: Drug: chlorpromazine and promethazine; Procedure: endovascular thrombectomy; Drug: rt-PA
Placebo groupPlacebo comparator50 ml saline solution was delivered intravenously at the beginning of endovascular thrombectomyat a velocity of 4ml/h. The whole period of drug delivery lasts for approximately 12h.
Receives: Drug: Placebo group; Procedure: endovascular thrombectomy; Drug: rt-PA

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. The incidence and severity of all adverse events (AEs) and severe adverse events (SAEs)

    AEs including:

    1. Severe hypothermia with body temperature<32 degree centigrade
    2. Severe hypotension with systolic blood pressure<90mmHg that needs additional support
    3. Any forms of intracranial hemorrhage
    4. Coma
    5. Death within 72h
    6. Respiratory depression defined as respiration rate<8 bpm/min
    7. Extrapyramidal symptoms including Parkinsonism, dystonia, dyskinesia.

    AEs are defined as severe adverse events(SAEs) if severity reaches grade 3-5 according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) ver. 5.0.

    Measured: 72 hours after randomization

Secondary outcomes (3)

  1. Scores of National institutes of health stroke scale (NIHSS)

    Scores on the National Institutes of Health Stroke Scale (NIHSS) range from 0 to 42, with higher scores indicating worse neurologic deficit.

    Measured: 24 hours after randomization

  2. Infarct volume

    Infarct volume is assessed by Computed Tomography and automatically calculated by software.

    Measured: 72 hours after randomization

  3. Plasma proteomics and metabolomics

    Proteomics and metabolomics will be performed using patients' plasma. The purpose is to determine what proteins or metabolites are mediated by C+P and correlated with favorable outcome.

    Measured: 24 hours±6 hours

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Oct 2024
  2. Study start9 Nov 2024
  3. Primary completionJan 2025 (estimated)
  4. Study completionFeb 2025 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
32 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06663631
Sponsor's protocol ID
CHILL-1
Acronym
CHILL-1
Status last verified
Dec 2024
First submitted
24 Oct 2024
Last updated
20 Dec 2024
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No: Because this study is an exploratory trial of dose-escalation, we want to decide whether to share the drug based on some of the problems and situations found during the study and the subject's personal decision. The purpose is to protect the privacy of the subjects and the implementation of the study.

Publications

  • 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.

    PubMed 27933367

  • 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.

    PubMed 31232236

  • 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.

    PubMed 33811844

  • 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.

    PubMed 35873710

  • 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.

    PubMed 31847503

  • 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.

    PubMed 33829970

  • 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.

    PubMed 33531913

  • 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.

    PubMed 33815250

  • 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.

    PubMed 36939736

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing chlorpromazine and promethazine, endovascular thrombectomy and rt-PA in people with Acute Ischemic Stroke, run by Capital Medical University at 1 site in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 20 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Xunming Ji, Doctor (+86 13911077166, Jixm@ccmu.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

The incidence and severity of all adverse events (AEs) and severe adverse events (SAEs) (time frame: 72 hours after randomization). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06663631, which also lists 9 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Dec 2024.

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