Aleeto in Acute ISchemic Stroke：A RandomISed Controlled Clinical Trial

Phase 2

Not yet recruiting

• Conditions: Acute Ischemic Stroke
• Interventions: Drug: Aleeto; Drug: Placebo

• Registration Number: NCT06759753
• Lead Sponsor: Beijing Tiantan Hospital

Brief Summary

This study is a prospective, double-blind, 1:1:1 randomized controlled study aimed at evaluating the efficacy and safety of Aleeto treatment compared to placebo in improving the NIHSS score at 14 days in patients with moderate to severe acute ischemic stroke. It also aims to explore the neuroprotective effects of Aleeto in moderate to severe acute ischemic stroke and provide data support and evidence for future clinical trials and evidence-based medicine.

Detailed Description

Stroke is the second leading cause of death worldwide, associated with high rates of morbidity, mortality, and disability. As a result, it places a significant social and economic burden on societies. Stroke is generally classified into two types: ischemic stroke and hemorrhagic stroke. Acute ischemic stroke (AIS) accounts for approximately 87% of all stroke cases, characterized by the sudden cessation of oxygen and blood supply to local cerebral tissue due to arterial occlusion.

According to the Global Burden of Disease study, in 2019, there were 28.76 million stroke patients in China, including 3.94 million new cases and 2.19 million deaths due to stroke. The burden of ischemic stroke (IS) in China has increased dramatically, with the Disability-Adjusted Life Years (DALYs) for IS rising by 138.6% from 1990 to 2019. This burden is expected to grow further due to the aging population, the persistently high incidence of stroke risk factors (such as hypertension), and inadequate management. Although significant advances have been made in the diagnosis and treatment of ischemic stroke in recent years-resulting in a notable reduction in recurrence rates-effective, targeted treatments to reduce disability and improve neurological recovery remain limited.

Aleeto, derived from cellular exosomes, is a group of specific protein polymers secreted by stem cells under stress. These exosomes possess several advantages, including selective assembly, targeted delivery, efficient tissue repair, high safety, stable chemical properties, and ease of preservation. Moreover, Aleeto has demonstrated strong potential for nerve repair.

This study is a single-center, randomized, double-blind, placebo-controlled clinical trial designed to evaluate the safety, tolerability, and preliminary efficacy of Aleeto in patients with acute ischemic stroke. The trial also aims to determine the appropriate dosage for future clinical studies.

A total of 192 patients will be enrolled and randomly assigned to three groups. All participants will receive standardized treatment according to clinical guidelines, along with ginkgo ester dropping pills (4 pills per dose, 3 times per day, for 90 days of oral treatment). The dosage and type of drugs used will remain consistent throughout the trial.

Experimental Group 1: Intravenous administration of Aleeto at 130 μg/day for 14 ± 2 days (130 μg Aleeto dissolved in 100 mL sodium chloride injection).

Experimental Group 2: Intravenous administration of Aleeto at 260 μg/day for 14 ± 2 days (260 μg Aleeto dissolved in 100 mL sodium chloride injection).

Placebo Group: A placebo with the same appearance, odor, and color as Aleeto will be administered in the same manner and for the same duration as the experimental groups.

Study Timeline

• Study First Submitted: 2024-12-29
• Study First Submitted QC: 2024-12-29
• Study First Posted: 2025-01-06
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-26
• Last Update Posted: 2025-02-28
• Study Start: 2025-03-15
• Primary Completion: 2025-11-30
• Study Completion: 2026-01-31

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 192

Inclusion Criteria

1. Age between 30 and 80 years (30 ≤ age ≤ 80).
2. Diagnosis of acute ischemic stroke confirmed by CT or MRI, according to the "Key Points for Diagnosis of Major Cerebrovascular Diseases in China 2019."
3. Time from symptom onset ≤ 72 hours.
4. NIHSS score between 6 and 24, with a score of ≥ 1 on items 5 and 6 of the NIHSS.
5. Pre-stroke mRS (modified Rankin Scale) < 2, indicating independent activities of daily living.
6. Signed informed consent.

Exclusion Criteria

1. Intracranial hemorrhagic diseases identified by head CT: cerebral hemorrhage, extradural hemorrhage, subarachnoid hemorrhage, intraventricular hemorrhage, etc.
2. Combined with other active and major neurological diseases (such as induced seizures, poor drug control of recurrent seizures, multiple sclerosis, intracranial tumors, etc.).
3. History of infectious diseases (HIV positive or positive test history, HCV antibody positive or positive test history, HBV surface antigen positive and/or serum HBV DNA positive or serum HBV DNA > 2 × 10^8 IU/ml).
4. Severe renal or hepatic insufficiency. (Severe hepatic insufficiency is defined as alanine aminotransferase (ALT) value>3 times normal upper limit or Aspartate aminotransferase (AST)>3 times normal upper limit; Severe renal insufficiency is defined as creatinine>1.5 times normal upper limit or creatinine clearance < 50 ml/min, or over stage 3 of chronic kidney disease), severe heart failure (New York Heart Association grades III - IV).
5. Resistant Hypertension, systolic pressure ≥220mmHg or diastolic pressure ≥120mmHg.
6. History of Hemostatic disorder, systemic bleeding, thrombocytopenia or neutropenia, drug-induced hematology or liver dysfunction, white blood cell count <2×10^9/L or platelet count <100×10^9/L.
7. History of severe anemia within the past 1 month (hemoglobin < 90g/L).
8. Body Mass Index (BMI) < 16kg/m2 or BMI> 35kg/m2.
9. Severe organic diseases with expected survival time <5 years, such as malignant tumor.
10. Women of child bearing potential, pregnant or breastfeeding.
11. Individual who have difficulty communicating verbally to the extent that they are unable to communicate, understand or follow instructions normally, and are unable to cooperate with treatment and evaluation.
12. Combined with alcohol and drug abuse history.
13. Known history of allergy to biological agents such as proteins and cell products.
14. History of intracranial or spinal surgery, major surgery, or severe physical trauma within the past 4 weeks.
15. Received any vaccinations within the past 28 days.
16. Use of other investigational drugs within 30 days or 5 drug half-lives.
17. Unable to complete follow-up due to geographical or other reasons.
18. The researchers believe that the patient is not suitable to participate in this study.
19. Participated in other clinical trials.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Experimental group 1	Aleeto	Intravenous administration of Aleeto at 130μg/day for 14±2 days (130μg Aleeto with 100 ml sodium chloride injection), along with Ginkgo Ester Dropping Pills, 4 pills per dose, 3 times/day, orally, for 90 days.
Placebo group	Placebo	Placebo with the same dosage form, odor and color as Aleeto was administered in the same way and course of treatment, along with Ginkgo Ester Dropping Pills, 4 pills per dose, 3 times/day, orally, for 90 days.
Experimental group 2	Aleeto	Intravenous administration of Aleeto at 130μg/day for 14±2 days (260μg Aleeto with 100 ml sodium chloride injection), along with Ginkgo Ester Dropping Pills, 4 pills per dose, 3 times/day, orally, for 90 days.

Primary Outcome Measures

Name	Time	Method
Change from baseline in NIH Stroke Scale	At 14 days after randomization	NIH Stroke Scale (NIHSS) scores from 0 to 42. A higher score indicates worse neural function.

Secondary Outcome Measures

Name	Time	Method
Change from baseline in Fugl-Meyer Assessment	At 14±2 and 90±7days after randomization.	Fugl-Meyer Assessment (FMA) socres from 0 to 226. A higher score indicates better motor function.
Change from baseline in NIH Stroke Scale	At 7±1 days after randomization.	NIH Stroke Scale (NIHSS) scores from 0 to 42. A higher score indicates worse neural function.
Change from baseline in Modified Rankin Scale	At 90±7days after randomization	Modified Rankin Scale (mRS) ranks from 0 to 5. A higher rank indicates worse neural function.
Change from baseline in Ashworth scale	At 14±2 and 90±7days after randomization.	Ashworth scale ranks from 0 to 5. A higher rank indicates worse motor function.
The ratio of modified Barthel index ≥95 points	At 90±7days after randomization.	Modified Barthel index socres from 0 to 100. A higher score indicates better self-care ability.
Change from baseline in Visual Analogue Scale	At 14±2 and 90±7days after randomization.	Visual Analogue Scale (VAS) ranks from 0 to 10. A higher rank indicates higher pain level.
Change from baseline in Montreal Cognitive Assessment	At 90±7days after randomization.	Montreal Cognitive Assessment (MoCA) socres from 0 to 30. A higher score indicates better cognitive function.
Combined vascular events	From randomization to the end of treatment at 90±7days	Including stroke (including ischemic and hemorrhagic stroke), myocardial infarction and cardiovascular death
New-onset Stroke Events	From randomization to the end of treatment at 90±7days	Including hemorrhagic and ischemic strokes
All-cause Mortality	From randomization to the end of treatment at 90±7 days

Trial Locations

Locations (1)

Beijing Tiantan Hospital; 🇨🇳 Beijing, China