iPSC-derived exosome treatment for Moyamoya disease

Phase I Clinical Trial of Induced Pluripotent Stem Cell-derived Extracellular Vesicles Combined With Temporal Muscle Flap Application in Promoting Intracranial and Extracranial Blood Flow Reconstruction in Patients With Moyamoya Disease

This Phase 1 trial will test whether applying iPSC-derived extracellular vesicles to the temporal muscle can help adults with Moyamoya disease who had a temporal muscle patch but still have inadequate blood flow.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 9 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Tongji Hospital (Academic / other)
• Locations: 1 site (Wuhan, Hubei)
• Trial ID: NCT07065409 on ClinicalTrials.gov

What this trial studies

This single-center Phase 1 interventional trial will deliver induced pluripotent stem cell–derived extracellular vesicles (iPSC-EVs) locally to the temporal muscle in adults with Moyamoya disease to promote angiogenesis. Participants are adults (18–75) with bilateral terminal ICA involvement and Suzuki score ≥3 who have undergone temporal muscle patch surgery without satisfactory improvement. The primary focus is safety and tolerability of the local iPSC-EV transplantation, with exploratory measures of improved muscle and cerebral perfusion. Procedures and follow-up visits will take place at Tongji Hospital in Wuhan.

Who should consider this trial

Good fit: Adults aged 18–75 with confirmed Moyamoya disease (bilateral terminal ICA stenosis/occlusion, ACA/MCA origin involvement), Suzuki score ≥3, who have had temporal muscle patch surgery without satisfactory improvement and meet standard lab criteria are ideal candidates.

Not a fit: Children, patients with early or mild disease (Suzuki <3), those who have not had a temporal muscle patch, or those with significant organ dysfunction are unlikely to be eligible or benefit from this intervention.

Why it matters

Potential benefit: If successful, the approach could boost collateral vessel formation in the temporal muscle and improve cerebral blood flow, potentially reducing ischemic symptoms or stroke risk.

How similar studies have performed: This application of iPSC-derived extracellular vesicles for Moyamoya is largely novel; related iPSC-EV and extracellular vesicle approaches have shown pro-angiogenic effects in preclinical studies but clinical evidence is limited.

Eligibility criteria

Inclusion criteria:

1. Diagnosed adult patients with MMD aged 18-75 years (inclusive), with bilateral terminal occlusion of the internal carotid arteries (ICA) and stenosis or occlusion of the anterior cerebral artery (ACA) and middle cerebral artery (MCA) at the origin, accompanied by the formation of abnormal vascular networks at the base of the skull, as indicated by head DSA or MRA. Unilateral or bilateral lesions are acceptable. Suzuki score ≥ 3.
2. Relevant bone marrow, liver, kidney, and heart function indicators meet the following standards (based on the normal values of the clinical trial center): absolute neutrophil count (ANC) ≥ 1.5×109/L, platelets ≥ 100×109/L, total serum bilirubin ≤ 1.5 times the upper limit of normal (ULN), ALT, AST, or ALP ≤ 3 times ULN; serum creatinine ≤ 1.5 times ULN, international normalized ratio (INR) ≤ 1.5 times ULN, APTT ≤ 1.5 times ULN.
3. Patients have undergone temporal muscle patch surgery and have not achieved satisfactory improvement in symptoms.
4. Patients have been followed up for ≥ 3 months since the surgery.
5. Vascular DSA performed 3 months after the surgery indicates poor blood flow reconstruction.
6. CTP or ASL performed 3 months after the surgery shows ischemia.
7. Patients still have clinical manifestations of cerebral ischemia or cerebral infarction due to MMD 3 months after the surgery.
8. Patients or their legal representatives have given informed consent and signed the informed consent form.

Exclusion criteria:

1. Patients with severe liver or kidney dysfunction or other complications;
2. Patients with a history of mental disorders or mental diseases;
3. Patients with coagulation disorders;
4. Patients with extensive cerebral infarction or in a coma;
5. Patients who only undergo direct bypass surgery;
6. Patients who have not signed the surgical consent form;
7. Patients with allergic constitutions or a clear history of allergies;
8. Pregnant women, lactating women, and patients with plans to conceive during the trial period;
9. Patients who have participated in other clinical trials in the past three months;
10. Patients deemed unsuitable for the trial by the researcher.

Where this trial is running

Wuhan, Hubei

• Tongji hospital — Wuhan, Hubei, China (Recruiting)

Study contacts

• Principal investigator: Huaqiu Zhang — Tongji Hospital
• Study coordinator: Huaqiu Zhang

Conditions Moyamoya Disease