Study of Neural Stem Cell-Derived Exosomes in Moderate-to-Severe Early-Onset Alzheimer's Disease

NCT07554872 | Not Yet Recruiting Phase 1 DMC

• 1 other identifier: SMHC-EOAD-NSCEV-2026-01
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open-label, single-center, phase I clinical study in patients with moderate-to-severe early-onset Alzheimer's disease. The study aims to evaluate the safety, tolerability, and preliminary efficacy of neural stem cell-derived exosomes (NSC-EVs) administered by the intranasal route. A total of 9 participants will be enrolled in 3 frequency-escalation groups: once every 3 days, once every other day, and once daily, each for 28 days. Participants will undergo screening and baseline assessment, a 28-day treatment period, and follow-up visits at 4, 8, and 24 weeks after the end of treatment.

Conditions

Alzheimer Disease (AD)

Keywords

Early-Onset Alzheimer's Disease; Moderate-to-Severe Alzheimer's Disease; Neural Stem Cell-Derived Exosomes; Intranasal Administration; Phase I Clinical Study; Frequency Escalation; Safety; Tolerability

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Treatment-Related Adverse Events

  Number of participants experiencing treatment-related adverse events assessed according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.

  Baseline to Week 4

• Number of Participants With Treatment-Related Clinical Laboratory Abnormalities

  Number of participants with treatment-related clinical laboratory abnormalities during the treatment period.

  Baseline to Week 4

Secondary Outcomes (8)

• Change in Chinese Mini-Mental Status (CMMS) Score

  Baseline, Week 4 (end of treatment), and 4, 8, and 24 weeks after end of treatment

• Change in Severe Impairment Battery (SIB) Score

  Baseline, Week 4 (end of treatment), and 4, 8, and 24 weeks after end of treatment

• Change in Neuropsychiatric Inventory (NPI) Score

  Baseline, Week 4 (end of treatment), and 4, 8, and 24 weeks after end of treatment

• Change in Geriatric Depression Scale (GDS) Score

  Baseline, Week 4 (end of treatment), and 4, 8, and 24 weeks after end of treatment

• Change in Pittsburgh Sleep Quality Index (PSQI) Score

  Baseline, Week 4 (end of treatment), and 4, 8, and 24 weeks after end of treatment

Study Arms (3)

Low-Frequency NSC-EVs

EXPERIMENTAL

Participants receive neural stem cell-derived exosomes by intranasal administration once every 3 days for 28 days. The single dose is 6 × 10\^9 particles administered into both nostrils. In the low-frequency group, dosing is scheduled on Days 1, 4, 7, 10, 13, 16, 19, 22, 25, and 28, for a total of 10 doses.

Biological: Neural Stem Cell-Derived Exosomes

Medium-Frequency NSC-EVs

EXPERIMENTAL

Participants receive neural stem cell-derived exosomes by intranasal administration every other day for 28 days. The single dose is 6 × 10\^9 particles administered into both nostrils. In the medium-frequency group, dosing is scheduled on Days 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, and 27, for a total of 14 doses.

Biological: Neural Stem Cell-Derived Exosomes

High-Frequency NSC-EVs

EXPERIMENTAL

Participants receive neural stem cell-derived exosomes by intranasal administration once daily for 28 days. The single dose is 6 × 10\^9 particles administered into both nostrils. In the high-frequency group, dosing is scheduled daily from Day 1 through Day 28, for a total of 28 doses.

Biological: Neural Stem Cell-Derived Exosomes

Interventions

Neural Stem Cell-Derived Exosomes BIOLOGICAL

The investigational product is a neural stem cell-derived exosome preparation administered intranasally. The product specification is 6 × 10\^9 particles per 2 mL vial. The product is thawed to room temperature before administration and delivered into both nostrils. The same investigational product is used in all study groups; the groups differ only in dosing frequency.

Also known as: NSC-EVs

High-Frequency NSC-EVs; Low-Frequency NSC-EVs; Medium-Frequency NSC-EVs

Eligibility Criteria

• Age: 50 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or postmenopausal female, aged 50 to 75 years.
• Meets the 2011 NIA-AA criteria for probable Alzheimer's disease dementia.
• Age at onset ≤65 years.
• CMMS score 5-20
• Stable dose for at least 2 months before enrollment if receiving pro-cognitive or psychiatric medications.
• Primary school education or above and able to complete study-required cognitive assessments.
• Hachinski Ischemic Score ≤4.
• GDS total score ≤10.
• Positive amyloid pathology confirmed by Aβ-PET at screening or before enrollment.
• Adequate vision and hearing to complete assessments.
• Has a reliable caregiver able to accompany the participant to study visits and provide information for assessments.
• Willing to participate and sign informed consent.

You may not qualify if:

• Dementia due to causes other than Alzheimer's disease.
• Brain MRI showing any of the following: Fazekas white matter hyperintensity score \>2; more than 2 lacunar infarcts \>1.5 cm; lacunar infarcts involving critical regions such as the thalamus, hippocampus, entorhinal cortex, or parahippocampal region; cerebral hemorrhage, subdural hematoma, aneurysm, arteriovenous malformation, intracranial mass lesion, or other clinically significant structural abnormalities.
• Allergy to stem cell-derived exosomes or PET examination.
• Severe psychiatric disorder or symptoms.
• Significant active physical illness, including severe cardiac disease, severe systemic infection, or severe liver/kidney dysfunction.
• Elevated tumor markers or tumor history.
• Immune-related disease.
• Significant nasal obstruction.
• Serious suicide risk.
• Participation in another clinical trial or stem cell therapy within the past 6 months.
• Any other condition judged inappropriate by the investigator.
• Contraindications to MRI or inability to complete MRI examinations, including non-MRI-compatible metallic implants, certain stents, plates, pacemakers, or severe claustrophobia.

Sponsors & Collaborators

• Shanghai Mental Health Center: lead
• Shanghai Angecon Biotechnology Co., Ltd.: collaborator

Study Sites (1)

Shanghai Mental Health Center

Shanghai, Shanghai Municipality, 200030, China

Location

MeSH Terms

Conditions

Alzheimer Disease

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Central Study Contacts

Yue Ling 岳玲, MD, PhD

CONTACT

18017311249; bellinthemoon@hotmail.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: This is a sequential, open-label, single-center phase 1 study using a 3+3 frequency-escalation design. Participants are enrolled from the lowest-frequency group to the highest-frequency group. Each group starts with 3 participants, including a sentinel participant, and escalation proceeds only after protocol-defined safety review. Expansion is permitted according to protocol-defined dose-limiting toxicity criteria.

Study Record Dates

• First Submitted: April 21, 2026
• First Posted: April 28, 2026
• Study Start: May 1, 2026
• Primary Completion (Estimated): October 20, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: May 4, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)