HUC-MSC-sEV-001 Nasal Drops for Neurodegenerative Diseases

Phase 1

Not yet recruiting

• Conditions: Alzheimer Disease; Parkinson Disease; Lewy Body Dementia; Multiple System Atrophy; Fronto-temporal Dementia
• Interventions: Drug: hUC-MSC-sEV-001 nasal drops

• Registration Number: NCT06607900
• Lead Sponsor: Xuanwu Hospital, Beijing

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.

Detailed Description

Not available

Study Timeline

• Status Verified: 2024-09
• Study First Submitted: 2024-09-19
• Study First Submitted QC: 2024-09-19
• Last Update Submitted: 2024-09-19
• Study First Posted: 2024-09-23
• Last Update Posted: 2024-09-23
• Study Start: 2024-11-01
• Primary Completion: 2027-08-31
• Study Completion: 2028-08-31

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

1. Age 40- 80;
2. Voluntarily sign informed consent;
3. Alzheimer's disease: 1)Probable AD as defined by the 2011 criteria of the National Institute on Alzheimer's Disease (NIA/AA); 2)Clinical Dementia Rating (CDR) score < 1.0; 3)Subjects have a reliable caregiver; 4)Stable treatment regimen for at least 1 month before treatment;
4. Parkinson'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 < 1.0;
7. Frontotemporal dementia: 1）Meet the 2017 International Research Society (IRS) diagnostic criteria for FTD; 2）CDR score < 1.0;

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
hUC-MSC-sEV-001 group	hUC-MSC-sEV-001 nasal drops	hUC-MSC-sEV-001 nasal drops treatment

Primary Outcome Measures

Name	Time	Method
Alzheimer's disease: Change in Alzheimer's disease assessment scale-cognitive section（ADAS-cog）	12 months	ADAS-Cog is comprised of 11 modalities that evaluate memory, praxis, and language deficiencies. The total score range is 0 to 70 points, with higher scores indicating greater cognitive impairment.
Parkinson's disease: Change in MDS Unified-Parkinson Disease Rating Scale(MDS-UPDRS)	12 months	The MDS-UPDRS is defined by 4 Parts, each composed by a different number of items. The MDS-UPDRS has a minimum score of 0 and a maximum score of 260. The higher the score, the more severe the impairment.
multiple system atrophy: Unified Multiple System Atrophy Rating Scale（Part I and Part II）	12 months	UMSARS is a clinical tool designed to assess the severity and progression of MSA. The scale is divided into multiple parts, with Part I focusing on functional disability based on the history and self-report symptoms and Part II the severity of motor symptoms through a physical examination. The higher score, the severer impairment.
lewy body dementia: Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC)	12 months	ADCS-CGIC provides a clinician-rated, subjective evaluation of a patient\'s cognitive, behavioral, and functional performance based on interviews and observations. The scoring typically uses a 7-point scale. The lower score, the better changes in overall condition.
frontotemporal dementia: CDR Dementia Staging Instrument PLUS National Alzheimer's Coordinating Center Behavior and Language Domains（CDR+NACC FTLD）	12 months	The CDR Dementia Staging Instrument provides a global assessment of cognitive and functional decline, while the NACC Behavior and Language Domains offer a more nuanced view of neuropsychiatric symptoms and language impairments.

Secondary Outcome Measures

Name	Time	Method
Barthel index	6 months, 12months	The Barthel Index is used for measuring a person\'s ability to perform basic activities of daily living.Scores typically range from 0 (totally dependent) to 100 (completely independent), with higher scores indicating greater independence in daily functioning.
mini mental status exam(MMSE)	6 months, 12months	The Mini-Mental State Examination (MMSE) is used for assessing cognitive function. The MMSE is scored out of a total of 30 points. A higher score indicates better cognitive function.
EQ-5D-5L	6 months, 12months	The EQ-5D-5L is used to measure health-related quality of life. The EQ-5D-5L assesses health on a scale of 0 to 25. A higher score means a lower quality of life.
Alzheimer's disease: sum of boxes of the CDR（CDR-SB）	6 months, 12months	The CDR-SB is used to assess the severity of cognitive impairment and dementia. The total score can range from 0 to 18, where higher scores indicate greater levels of impairment across the domains.
Alzheimer's disease: Alzheimer's Disease Cooperative Study - Activities of Daily Living （ADCS-ADL）	6 months, 12months	The ADCS-ADL is used to assess functional decline in patients with Alzheimer's disease, especially in the mild to moderate stages. The total score ranges from 0 to 78 , with higher scores indicating greater functional independence.
multiple system atrophy: Composite Autonomic Symptom Score	6 months, 12months	The COMPASS questionnaire is used to evaluate autonomic dysfunction, which can present with a variety of symptoms.Higher scores indicate greater impairment in autonomic function.
Clinical Global Impression	6 months, 12months	CGI is used to assess the severity of a patient's illness, the change in their condition over time, and the efficacy of treatments. It is scored on a 7-point scale, with a higher score indicating a worsen condition.
lewy body dementia: MDS-UPRDS	6 months, 12months
Lewy body dementia：Neuropsychiatric Inventory（NPI）	6 months, 12months	NPI is used to assess neuropsychiatric symptoms and behavioral disturbances in individuals. The Total NPI Score ranges from 0 to 144. Higher scores indicate greater overall severity of neuropsychiatric disturbances.
frontotemporal dementia: NPI	6 months, 12months
frontotemporal dementia: ADAS-cog	6 months, 12months
Adverse effects	3months, 6 months, 12months, 24months

Trial Locations

Locations (1)

Xuanwu Hospital, Capital Medical University; 🇨🇳 Beijing, Beijing, China