Induced Pluripotent Stem Cells-derived Small Extracellular Vesicles May Promote Neurological Function and Improve Cognitive Impairment in Acute Ischemic Stroke Patients

Overview

This study primarily evaluates whether iEV nasal administration can improve neurological impairment and cognitive dysfunction in patients with acute cerebral infarction and cognitive impairment, and preliminarily explores its clinical efficacy.

Detailed description

1. It is planned to enroll 40 patients with post - stroke cognitive impairment (PSCI, i.e., acute ischemic stroke (AIS) combined with cognitive impairment) who are hospitalized in the Department of Neurology and Stroke Ward of Shanghai Sixth People's Hospital. These patients should have had an AIS onset within 14 days. They will be divided into the PSCI + treatment group and the PSCI + control group according to a random number table, with 20 patients in each group. 2. Enrolled patients need to first complete blood tests such as blood routine and blood biochemistry, as well as skull MRI or skull CT examinations. The total course of treatment for both groups will be 12 weeks. 3. Both the treatment group and the control group will receive conventional basic treatment for cerebrovascular diseases. In addition, the treatment group will be given intranasal iEV administration, twice a week, 2 ml each time (with a concentration of 2×10¹⁰/ml), for 12 consecutive weeks. Before treatment and 12 weeks after treatment, the severity of neurological impairment, self - care ability, disability status, and cognitive function status will be evaluated to assess the therapeutic effect of iEV on neurological impairment and cognitive dysfunction in PSCI patients. 4. Before intranasal iEV treatment and 12 weeks after treatment, blood samples will be collected respectively to detect changes in indicators such as nerve cell damage, pro - inflammatory factors, angiogenesis, and blood - brain barrier disruption, so as to clarify the neuroprotective mechanism of iEV in PSCI patients.

Interventions

• Biological iEV
  Intranasal administration of iEV, twice a week, 2 ml each time (at a concentration of 2×10¹⁰/ml), for 12 consecutive weeks.
• Other Basic treatments
  Basic treatments for cerebrovascular diseases such as antiplatelet aggregation, blood pressure control, blood glucose control, blood lipid control, and plaque stabilization.

Primary outcome measures

• NIHSS [Time frame: From enrollment to the end of treatment at 12 weeks]
• mRS [Time frame: From enrollment to the end of treatment at 12 weeks]
• ADL [Time frame: From enrollment to the end of treatment at 12 weeks]
• MoCA [Time frame: From enrollment to the end of treatment at 12 weeks]
• MMSE [Time frame: From enrollment to the end of treatment at 12 weeks]

Secondary outcome measures (3)

• Indicators of pro-inflammatory factors [Time frame: From enrollment to the end of treatment at 12 weeks]
• Indicators of blood-brain barrier disruption [Time frame: From enrollment to the end of treatment at 12 weeks]
• Indicators of neuronal injury [Time frame: From enrollment to the end of treatment at 12 weeks]

Eligibility criteria

Inclusion criteria

• Age ≥ 18 years old.
• Diagnosed with acute ischemic stroke (AIS) according to WHO criteria.
• Time from onset to enrollment ≤ 2 weeks (stable condition after admission and able to cooperate with cognitive assessment), accompanied by manifestations of cognitive impairment, with a score of < 26 on the Montreal Cognitive Assessment (MoCA) scale.
• Cerebral MRI or CT scan shows stroke lesions related to the condition.
• Subjects or their family members voluntarily participate and sign the informed consent form.

Exclusion criteria

• A diagnosis of cognitive impairment prior to the onset of AIS;
• Presence of aphasia, hearing impairment, visual impairment, dysarthria, or other conditions that prevent completion of neuropsychological assessments;
• Patients with mental illnesses such as depression, anxiety disorder, or schizophrenia;
• Patients with severe diseases of the heart, liver, lungs, kidneys, or other vital organs;
• Patients with disturbed consciousness, a history of long-term alcohol consumption, a history of severe head trauma, or those who cannot cooperate with cognitive function tests for various reasons;
• illiterate patients.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Shanghai Sixth People's Hospital — Shanghai

Identifiers

NCT: NCT07145294 · 2024-100-（1）

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗