Sodium Valproate in Patients With Acute Ischemic Stroke

February 19, 2024 updated by: Peiying Li, RenJi Hospital

Sodium Valproate in Patients With Acute Ischemic Stroke: a Pilot Randomized Trial

The purpose of this pilot trial is to investigate the feasibility, safety, and efficacy of sodium valproate in patients with acute ischemic stroke, and also explore the mechanism: whether valproate increases peripheral anti-inflammatory CD177+ neutrophil levels.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Ischemic stroke is one of the leading causes of disability and mortality worldwide, which imposes a huge burden on families and society. Currently, the effective treatment strategies of ischemic stroke are limited. It is of great clinical value and significance to explore effective neuroprotective medications besides reperfusion therapy.

Sodium valproate is widely used in clinical practice, and its safety and tolerability has been confirmed. It is mainly used in the treatment of epilepsy, bipolar disorder, neuropathic pain and other diseases. In recent years, a number of preclinical studies have found that valproic acid has a potential neuroprotective effect in acute ischemic brain injury, which can decrease infarct volume, reduce blood-brain barrier damage, and improve neurological function. However, the neuroprotective mechanism of sodium valproate has not been fully revealed, and there is still a lack of clinical studies to clarify the neuroprotective effect of sodium valproate in patients with ischemic stroke.

The goal of this study is to test whether sodium valproate could become a new therapeutic approach for ischemic stroke. This prospective pilot study is intended to investigate the feasibility, safety, and efficacy of sodium valproate in patients with acute ischemic stroke, thus support the estimate of sample size for a future full trial. In addition, we will test the hypotheses that valproate increases peripheral anti-inflammatory CD177+ neutrophil levels.

Patients with acute ischemic stroke included in the study will be randomly assigned to sodium valproate group (20 mg/kg/d) or saline placebo group. Treatment will be started within 24 hours after stroke onset. The trial drug will be given intravenously for 3 consecutive days. The investigators evaluate whether sodium valproate can improve clinical outcomes and increase peripheral CD177+ neutrophil levels.

Study Type

Interventional

Enrollment (Estimated)

40

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Shanghai
      • Shanghai, Shanghai, China, 200127
        • Recruiting
        • Renji Hospital, Shanghai Jiao Tong University School of Medicine
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. 18≤age<75 years;
  2. Admitted to hospital within 24 hours after the onset of neurological impairment symptoms consequent to acute ischemic stroke diagnosed by CT or MRI;
  3. Not suitable for thrombolysis and mechanical thrombectomy;
  4. Written informed consent.

Exclusion Criteria:

  1. mRS ≥ 2 before the disease onset;
  2. Refractory hypertension (SBP>180mmHg or DBP>110mmHg after antihypertensive treatment);
  3. History of cerebral hemorrhage, intracranial tumor, cerebral arteriovenous malformation and aneurysm;
  4. History of brain trauma, intracranial or spinal surgery within 3 months, major surgery or severe physical trauma within 1 month;
  5. Signs of infection at time of admission;
  6. History of malignancy or active autoimmune disease;
  7. Use of glucocorticoids or other immunosuppressive medications;
  8. Contraindications to sodium valproate: pregnancy; liver disease or severe hepatic insufficiency (ALT, AST 3 times higher than the upper normal limit); hemorrhagic risk (such as platelet count <100x109/L, APTT≥35s); allergy to sodium valproate, sodium divalproate, or valproamide; hepatic porphyria; combined use of mefloquine; mitochondrial diseases related to POLG mutations; known disorders of the urea cycle;
  9. Use of medications containing active ingredients that can be converted to valproic acid, including sodium divalproate and valproamide;
  10. Contraindications or intolerance for CT perfusion imaging;
  11. Participating in other conflicting clinical trials;
  12. Any other condition that investigators consider unsuitable such as mental illness, cognitive impairment, or inability to follow trial procedures.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo group
Within 3 days after admission, normal saline will be given daily in the same way.
Drug: Normal saline
Patients with acute ischemic stroke included in the study are randomly assigned to low-dose sodium valproate group, high-dose sodium valproate group and placebo group. Besides receiving conventional treatment for stroke, 10mg/kg sodium valproate, 20mg/kg sodium valproate or normal saline were given intravenously for 3 consecutive days, respectively.
Experimental: Sodium valproate group
Within 3 days after admission, 20mg/kg sodium valproate will be given daily. Specifically, 400mg sodium valproate will be infused within 5 minutes, followed by intravenous drip with 1mg/kg/h.
Drug: Sodium valproate
Patients with acute ischemic stroke included in the study are randomly assigned to low-dose sodium valproate group, high-dose sodium valproate group and placebo group. Besides receiving conventional treatment for stroke, 10mg/kg sodium valproate, 20mg/kg sodium valproate or normal saline were given intravenously for 3 consecutive days, respectively.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Favorable outcome at 90 days (the Modified Rankin Scale (mRS) score≤2)
Time Frame: Day 90
The proportion of patients with favorable outcome, which is defined as the Modified Rankin Scale (mRS) score 0-2.
Day 90

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Favorable outcome at 30 days (the Modified Rankin Scale (mRS) score≤2)
Time Frame: Day 30
The proportion of patients with favorable outcome, which is defined as the Modified Rankin Scale (mRS) score 0-2.
Day 30
NIH Stroke Scale (NIHSS) score at 3 days
Time Frame: Day 3
The NIH Stroke Scale (NIHSS) score ranges from 0 to 42, where high scores mean a worse outcome.
Day 3
NIH Stroke Scale (NIHSS) score at 7 days
Time Frame: Day 7
The NIH Stroke Scale (NIHSS) score ranges from 0 to 42, where high scores mean a worse outcome.
Day 7
Changes of lesion volume from baseline to day 7
Time Frame: Day 7
The infarct lesion volume will be measures on magnetic resonance imaging DWI and FLAIR.
Day 7

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
The peripheral CD177+ neutrophil levels
Time Frame: Day 3 and Day 7
The CD177+ neutrophil levels in peripheral blood will be evaluated using flow cytometry.
Day 3 and Day 7
The levels of inflammatory cytokines in peripheral blood
Time Frame: Day 3 and Day 7
IL-1β、IL-2、IL-4、IL-5、IL-6、IL-8、IL-10、IL-12、IL-17A、IFN-α、IFN-γ、TNF-α
Day 3 and Day 7

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

RenJi Hospital

Investigators

  • Principal Investigator: Peiying Li, Doctor, Renji Hospital
  • Principal Investigator: Jieqing Wan, Doctor, Renji Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 1, 2023

Primary Completion (Estimated)

April 30, 2024

Study Completion (Estimated)

April 30, 2024

Study Registration Dates

First Submitted

August 14, 2023

First Submitted That Met QC Criteria

August 26, 2023

First Posted (Actual)

September 1, 2023

Study Record Updates

Last Update Posted (Actual)

February 21, 2024

Last Update Submitted That Met QC Criteria

February 19, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • LY2023-138-A

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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