About this trial
Moyamoya disease is a cerebrovascular disease clinically characterized by chronic progressive stenosis or occlusion at the ends of bilateral internal carotid arteries and the origin of anterior cerebral arteries and middle cerebral arteries, followed by the formation of abnormal vascular networks at the base of the skull. Clinically, patients with Moyamoya disease mainly present with ischemic or hemorrhagic stroke, and there are two peaks of incidence in children aged 3-5 and middle-aged people aged 40-50. Moreover, as the pathogenesis and treatment evaluation of Moyamoya disease are still in the research trough at present, new discoveries are prone to occur and thus attract a great deal of attention. It not only has a beneficial promoting effect on the treatment and diagnosis of patients, but also makes it easier for research topics to be reported in top journals.
This study intends to combine iPSC-EVs local skin transplantation with temporal muscle application to promote muscle angiogenesis and the establishment of extracranial and intracranial collateral circulation after temporal muscle application. The above-mentioned design features high efficiency, safety and convenience, and is an innovative exploration both at home and abroad. We hope to screen out safe, efficient and simple preparation methods and transplantation methods of iPSC-EVs through systematic experiments, establish an effective clinical evaluation system, and provide auxiliary means for intracranial and extracranial blood flow reconstruction surgery in the treatment of Moyamoya disease. Moreover, in terms of topic selection, iPSC is currently one of the most promising directions for innovative treatment worldwide.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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.
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.
Patients have undergone temporal muscle patch surgery and have not achieved satisfactory improvement in symptoms.
Patients have been followed up for ≥ 3 months since the surgery.
Disqualifiers
Patients with severe liver or kidney dysfunction or other complications;
Patients with a history of mental disorders or mental diseases;
Patients with coagulation disorders;
Patients with extensive cerebral infarction or in a coma;
Trial design
Single group
Treatments tested in this trial
iPSC-EVs
Biological/VaccineiPSC-EVs,The drug number is NouvSoma002-01. It is from iRegene Therapeutics Co., Ltd.
Treatment groups
Trial outcomes
Primary outcomes
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Evaluate the tolerance and adverse reactions of patients after 3 days, 2 weeks and 1 month of iPSC-EVs treatment. Incidence of Treatment-Emergent Adverse Events \[Safety and Tolerability\].
Imaging examinations
Imaging examinations were conducted on the patients before iPSC-EVs treatment, and at 1 month after treatment. Imaging examinations: MRI and TCD.
Neuropsychological tests
Neuropsychological tests were conducted on the patients before iPSC-EVs treatment, and at 1 month after treatment. neuropsychological tests: mRS, MMSE and MoCA
Secondary outcomes
Imaging examinations
Imaging examinations for post-treatment imaging assessment of blood flow reconstruction function. Imaging examinations: DSA, MRI, CTP, TCD, HR-VWI, and CT.
Neuropsychological tests
Neuropsychological tests for post-treatment imaging assessment of blood flow reconstruction function. neuropsychological tests: mRS, MMSE and MoCA
Sponsors and contacts
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Huaqiu Zhang
Lead sponsor
Tongji Hospital
Sponsor institution