MSC-Exosome Therapy for Frontotemporal Dementia

NCT07638813 | Not Yet Recruiting Phase 1 DMC

• 1 other identifier: 2026-221
• Study Type: interventional
• Target: 33
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study is testing a new treatment for Frontotemporal Dementia (FTD) - a progressive brain disease that affects personality, behavior, and language. Currently, there is no cure for FTD and no approved medication that can slow down or stop the disease. Existing treatments only help manage some symptoms temporarily. The investigational treatment in this study is made from exosomes - tiny particles naturally released by umbilical cord stem cells. Exosomes act like "message carriers" between cells. Researchers believe they may help protect brain cells, reduce harmful protein buildup, and improve brain function. The exosomes will be given as a nasal spray (sprayed into the nose). This method may allow the treatment to reach the brain directly without needing to pass through the blood-brain barrier (a natural protective layer that often blocks medications from entering the brain).

Conditions

Frontotemporal Dementia

Keywords

Frontotemporal Dementia; exosomes

Outcome Measures

Primary Outcomes (2)

• Clinical Efficacy: Change in CDR plus NACC FTLD Score

  Change from baseline in the Clinical Dementia Rating (CDR®) Dementia Staging Instrument plus the National Alzheimer's Coordinating Center Frontotemporal Lobar Degeneration (NACC FTLD) module total score at Week 24. Scale Range: Minimum = 0, Maximum = 30 Interpretation: A higher score indicates worse cognitive and behavioral function; a decrease (negative change) from baseline indicates improvement.

  Baseline and Week 24

• Safety and Tolerability: Incidence of Adverse Events

  Number of participants with treatment-emergent adverse events (AE), serious adverse events (SAE), adverse drug reactions (ADR), and serious adverse drug reactions (SADR), including assessment of causality and severity. Adverse events include local nasal reactions (e.g., epistaxis, nasal congestion, rhinorrhea, cough, pharyngeal discomfort, sneezing, nasal dryness) and systemic reactions (e.g., rash, pruritus, facial/eyelid swelling, dyspnea, chest tightness, fever, chills). Severity graded as mild, moderate, or severe.

  Baseline through Week 24 (end of treatment)

Secondary Outcomes (8)

• Change in Global Cognition: MMSE Score

  Baseline, Week 12, Week 24

• Change in Global Cognition: MoCA Score

  Baseline, Week 12, Week 24

• Change in Language Function: BNT Score

  Baseline, Week 12, Week 24

• Change in Language Function: Semantic Fluency Test

  Baseline, Week 12, Week 24

• Change in Neuropsychiatric Symptoms: NPI Score

  Baseline, Week 12, Week 24

Other Outcomes (4)

• Change in Brain Structure: Regional Brain Volume

  Baseline，and Week 24

• Change in Brain Function: Resting-State Functional Connectivity

  Baseline and Week 24

• Change in Plasma Biomarker: Neurofilament Light Chain (NfL)

  Baseline，Week 24

Study Arms (3)

Placebo Comparator

PLACEBO COMPARATOR

Participants randomized to the placebo group will receive intranasal spray of normal saline (0.9% sodium chloride), 1 mL per administration, twice weekly for 24 consecutive weeks. The placebo is identical in appearance, packaging, and administration procedure to the active investigational product to maintain blinding.

Other: Placebo Comparator (0.9% NaCl)

Low-Dose Exosome Group

EXPERIMENTAL

Participants randomized to the low-dose group will receive intranasal spray of human umbilical cord mesenchymal stem cell-derived exosomes (MSC-Exos), 1 mL per administration containing 24 × 10⁹ particles, twice weekly for 24 consecutive weeks.

Biological: Umbilical Cord Mesenchymal Stem Cell-Derived Exosomes （Low-Dose）

High-Dose MSC-Exosome

EXPERIMENTAL

Participants randomized to the high-dose group will receive intranasal spray of human umbilical cord mesenchymal stem cell-derived exosomes (MSC-Exos), 1 mL per administration containing 24 × 10⁹ particles, three times weekly for 24 consecutive weeks. Enrollment in this arm will only begin after the first 3 participants in the low-dose arm complete the 4-week safety lead-in and 21-day safety observation period without dose-limiting toxicity or serious adverse events.

Biological: Umbilical Cord Mesenchymal Stem Cell-Derived Exosomes （High-Dose）

Interventions

Umbilical Cord Mesenchymal Stem Cell-Derived Exosomes （Low-Dose） BIOLOGICAL

Participants randomized to the low-dose group will receive intranasal spray of human umbilical cord mesenchymal stem cell-derived exosomes (MSC-Exos), 1 mL per administration containing 24 × 10⁹ particles, twice weekly for 24 consecutive weeks.

Low-Dose Exosome Group

Umbilical Cord Mesenchymal Stem Cell-Derived Exosomes （High-Dose） BIOLOGICAL

Participants randomized to the high-dose group will receive intranasal spray of human umbilical cord mesenchymal stem cell-derived exosomes (MSC-Exos), 1 mL per administration containing 24 × 10⁹ particles, three times weekly (e.g., Monday, Wednesday, Friday) for 24 consecutive weeks. Enrollment in this arm will only begin after the first 3 participants in the low-dose arm complete the 4-week safety lead-in and 21-day safety observation period without dose-limiting toxicity or serious adverse events.

High-Dose MSC-Exosome

Placebo Comparator (0.9% NaCl) OTHER

Participants randomized to the placebo group will receive intranasal spray of normal saline (0.9% sodium chloride), 1 mL per administration, twice weekly for 24 consecutive weeks. The placebo is identical in appearance, packaging, and administration procedure to the active investigational product to maintain blinding.

Placebo Comparator

Eligibility Criteria

• Age: 30 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of probable frontotemporal dementia (FTD), including behavioral variant (bvFTD), semantic variant primary progressive aphasia (svPPA), or non-fluent variant primary progressive aphasia (nfvPPA), according to established diagnostic criteria, with supportive neuroimaging evidence showing frontal and/or temporal lobe atrophy score of 2 or higher on brain CT or MRI.
• Age between 30 and 80 years (inclusive) at screening.
• Study partner who agrees to participate in the study, provides at least 3 hours of daily care or visits, and can manage all study medication.
• Frontotemporal Lobar Degeneration Clinical Dementia Rating (FTLD-CDR) score of 0-2 and Mini-Mental State Examination (MMSE) score greater than 10 at screening.
• Stable use of cognition- or behavior-related medications (e.g., cholinesterase inhibitors, memantine, antidepressants, antipsychotics, mood stabilizers, benzodiazepines) for at least 30 days before baseline.
• Signed informed consent form.

You may not qualify if:

• History of stroke or other neurological or psychiatric disorder (other than FTD) that is considered the primary cause of behavioral symptoms.
• Pregnancy or breastfeeding, or plan to become pregnant during the study period.
• Use of any investigational or experimental drug or device within 60 days or 5 half-lives (whichever is longer) prior to screening.
• Presence of speech or language impairment that severely affects the implementation of neuropsychological assessments or safety evaluations per the study protocol.
• History of cancer, unless: (a) considered cured; (b) not actively receiving anti-cancer therapy or radiation and the investigator judges that treatment is unlikely to be needed in the next 5 years; or (c) for prostate cancer or basal cell carcinoma, no significant progression in the past 2 years.
• Any clinically significant hematologic, endocrine, cardiovascular, renal, hepatic, gastrointestinal, or neurological disease that would interfere with study participation. Participants may be included if the condition has been stable for at least one year and the investigator judges that it does not affect participation.
• Known hypersensitivity to the study drug or any of its excipients.

Sponsors & Collaborators

• Ruijin Hospital: lead

MeSH Terms

Conditions

Frontotemporal Dementia

Condition Hierarchy (Ancestors)

Frontotemporal Lobar Degeneration; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; TDP-43 Proteinopathies; Neurodegenerative Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases; Neurocognitive Disorders; Mental Disorders

Study Officials

• Shengdi Chen, MD, Ph.D

  Department of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Chao Gao, MD，Ph.D

CONTACT

+8618217590273; anshangaochao@163.com

Shengdi Chen, MD, Ph.D

CONTACT

+8613818018166; chensd@rjh.com.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Physician

Study Record Dates

• First Submitted: June 2, 2026
• First Posted: June 10, 2026
• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): October 31, 2027
• Study Completion (Estimated): October 31, 2027
• Last Updated: June 10, 2026

Record last verified: 2026-06