Clinical trial NCT06607900: HUC-MSC-sEV-001 Nasal Drops for Neurodegenerative Diseases
Official title: A Multi-center, Open, Single-arm, Basket-design Clinical Trial to Evaluate the Safety and Efficacy of Human Umbilical Cord Mesenchymal Stem Cell-derived Small Extracellular Vesicles HUC-MSC-sEV-001 Nasal Drops for the Treatment of Multiple Neurodegenerative Diseases
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
Conditions: Alzheimer Disease
Parkinson Disease
Lewy Body Dementia
Multiple System Atrophy
Fronto-temporal Dementia
Lead sponsor: Xuanwu Hospital, Beijing
Sponsor class: OTHER
First posted: 2024-09-23
Enrollment: 100
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: To evaluate the safety and preliminary efficacy of human umbilical cord mesenchymal stem cell-derived small extracellular vesicles hUC-MSC-sEV-001 nasal drops in multiple neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, multiple system atrophy, Lewy body dementia, and frontotemporal dementia.


Eligibility criteria: Inclusion Criteria:

1. Age 40- 80;
2. Voluntarily sign informed consent;
3. Alzheimer\&#39;s disease: 1)Probable AD as defined by the 2011 criteria of the National Institute on Alzheimer\&#39;s Disease (NIA/AA); 2)Clinical Dementia Rating (CDR) score \&lt; 1.0; 3)Subjects have a reliable caregiver; 4)Stable treatment regimen for at least 1 month before treatment;
4. Parkinson\&#39;s disease: 1)Patients diagnosed with PD according to the 2015 MSD PD diagnostic criteria; 2)Hoehn and Yahr scale ≤ grade 3; 3)Stable treatment regimen for at least 1 month before drug administration;
5. Multiple system atrophy:1)Diagnosed as possible or probable multiple system atrophy; 2)Diagnosed less than 3 years from baseline, with an expected survival of at least 3 years; 3)Stable treatment regimen for at least 1 month before drug administration;
6. Lewy body dementia: 1)Meet the revised DLB consensus criteria (the fourth diagnostic consensus of the DLB Alliance in 2017). 2)The severity of motor symptoms must be less than or equal to grade 3 in the Hoehn and Yahr scale; 3)CDR score \&lt; 1.0;
7. Frontotemporal dementia: 1）Meet the 2017 International Research Society (IRS) diagnostic criteria for FTD; 2）CDR score \< 1.0;

Exclusion Criteria:

1. Subjects who have received allogeneic mesenchymal progenitor cell therapy or its derived small extracellular vesicles;
2. Suffering from other uncontrolled diseases that may interfere with the study results, including but not limited to infection, hypertension, diabetes, mental illness, etc.;
3. Combined with malignant tumors, hematological malignancies or other serious systemic diseases;
4. Clinically obvious history of allergic reactions, especially drug allergic reactions;
5. Severe renal insufficiency, creatinine clearance \&lt; 30 mL/min;
6. Severe liver insufficiency: serum aspartate aminotransferase ≤ 2.5 times the upper limit of normal; serum alanine aminotransferase ≤ 2.5 times the upper limit of normal;
7. HBsAg, or HBcAb positive and HBV DNA positive, hepatitis C virus antibody positive, peripheral blood hepatitis C virus RNA positive, HIV antibody positive; CMV DNA positive, syphilis positive.
8. Women of childbearing age who do not intend to take effective contraceptive measures during the trial or within 90 days of the last dose and have a positive pregnancy test record, as well as pregnant or lactating women, or men who are sexually active during the trial or within 90 days of the last dose and do not intend to take effective contraceptive measures, or men who plan to donate sperm during the trial or within 90 days of the last dose;
9. Undergoing investigational drug trials;
10. Participated in other clinical drug studies in the past 30 days;
11. There are situations that the investigator believes cannot understand and/or comply with the study procedures and/or follow-up.
12. Alzheimer\&#39;s disease: 1) Major history of major brain injury with persistent neurological impairment (with or without) or known brain structural abnormalities. 2)Cognitive impairment caused by other reasons: central nervous system infection, Creutzfeldt-Jakob disease, traumatic dementia, other physical and chemical factors (such as drug poisoning, alcoholism, carbon monoxide poisoning, etc.), major physical diseases (such as hepatic encephalopathy, pulmonary encephalopathy, etc.), intracranial space-occupying lesions (such as subdural hematoma, brain tumor), endocrine disorders (such as thyroid disease, parathyroid disease) and vitamin B12, folic acid deficiency or any other known causes.
13. Parkinson\&#39;s disease: Parkinson\&#39;s syndrome other than PD, including but not limited to progressive supranuclear gaze palsy, multiple system atrophy, vascular parkinsonism, drug-induced Parkinson\&#39;s disease, essential tremor, primary dystonia.
14. Multiple system atrophy: 1)Modified Unified Multiple System Atrophy Rating Scale (UMSARS) I score ≥14; 2)The presence of conditions that the investigators believe affect the diagnosis or assessment of MSA.
15. Lewy body dementia: 1)Patients currently diagnosed with any primary psychiatric disorder (such as schizophrenia, bipolar disorder, or major depressive episode) according to DSM-V; 2)Patients with clinically significant or unstable systemic illness and exposure to toxicants in the past 5 years.
16. Frontotemporal dementia: Diagnosis of severe central nervous system disease other than FTD, which may be the cause of the patient\&#39;s FTD symptoms or may affect the study objectives.

Primary outcomes:
measure: Alzheimer's disease: Change in Alzheimer's disease assessment scale-cognitive section（ADAS-cog）
timeFrame: 12 months
measure: Parkinson's disease: Change in MDS Unified-Parkinson Disease Rating Scale(MDS-UPDRS)
timeFrame: 12 months
measure: multiple system atrophy: Unified Multiple System Atrophy Rating Scale（Part I and Part II）
timeFrame: 12 months
measure: lewy body dementia: Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC)
timeFrame: 12 months
measure: frontotemporal dementia: CDR Dementia Staging Instrument PLUS National Alzheimer's Coordinating Center Behavior and Language Domains（CDR+NACC FTLD）
timeFrame: 12 months
Secondary outcomes:
measure: Barthel index
timeFrame: 6 months, 12months
measure: mini mental status exam(MMSE)
timeFrame: 6 months, 12months
measure: EQ-5D-5L
timeFrame: 6 months, 12months
measure: Alzheimer's disease: sum of boxes of the CDR（CDR-SB）
timeFrame: 6 months, 12months
measure: Alzheimer's disease: Alzheimer's Disease Cooperative Study - Activities of Daily Living （ADCS-ADL）
timeFrame: 6 months, 12months
measure: multiple system atrophy: Composite Autonomic Symptom Score
timeFrame: 6 months, 12months
measure: Clinical Global Impression
timeFrame: 6 months, 12months
measure: lewy body dementia: MDS-UPRDS
timeFrame: 6 months, 12months
measure: Lewy body dementia：Neuropsychiatric Inventory（NPI）
timeFrame: 6 months, 12months
measure: frontotemporal dementia: NPI
timeFrame: 6 months, 12months
measure: frontotemporal dementia: ADAS-cog
timeFrame: 6 months, 12months
measure: Adverse effects
timeFrame: 3months, 6 months, 12months, 24months
Other outcomes:
Locations:
city: Beijing
country: China
facility: Xuanwu Hospital, Capital Medical University
state: Beijing
Study officials:
References: