Frontotemporal Dementia
Conditions
Keywords
Frontotemporal Dementia, exosomes
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).
Interventions
BIOLOGICALUmbilical Cord Mesenchymal Stem Cell-Derived Exosomes （Low-Dose）
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.
BIOLOGICALUmbilical Cord Mesenchymal Stem Cell-Derived Exosomes （High-Dose）
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 36 × 10⁹ particles, twice 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 period without dose-limiting toxicity or serious adverse events.
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.
Sponsors
Ruijin Hospital
ECHO Biotech
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
30 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. 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. 2. Age between 30 and 80 years (inclusive) at screening. 3. 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. 4. Frontotemporal Lobar Degeneration Clinical Dementia Rating (FTLD-CDR) score of 0-2 and Mini-Mental State Examination (MMSE) score greater than 10 at screening. 5. 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. 6. Signed informed consent form.
Exclusion criteria
1. History of stroke or other neurological or psychiatric disorder (other than FTD) that is considered the primary cause of behavioral symptoms. 2. Pregnancy or breastfeeding, or plan to become pregnant during the study period. 3. Use of any investigational or experimental drug or device within 60 days or 5 half-lives (whichever is longer) prior to screening. 4. Presence of speech or language impairment that severely affects the implementation of neuropsychological assessments or safety evaluations per the study protocol. 5. 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. 6. 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. 7. Known hypersensitivity to the study drug or any of its excipients.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Efficacy: Change in CDR plus NACC FTLD Score | Baseline and Week 24 | 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. |
| Safety and Tolerability: Incidence of Adverse Events | Baseline through Week 24 (end of treatment) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Global Cognition: MMSE Score | Baseline, Week 12, Week 24 | Change from baseline in Mini-Mental State Examination (MMSE) total score. Range: 0-30, with higher scores indicating better cognitive function. |
| Change in Global Cognition: MoCA Score | Baseline, Week 12, Week 24 | Change from baseline in Montreal Cognitive Assessment (MoCA) Basic Version total score. Range: 0-30, with higher scores indicating better cognitive function. |
| Change in Language Function: BNT Score | Baseline, Week 12, Week 24 | Change from baseline in Boston Naming Test (BNT) total score, measuring confrontation naming ability. Unabbreviated Scale Title: Boston Naming Test (BNT) Scale Range: Minimum = 0, Maximum = 60 Interpretation: Higher scores indicate better language function; an increase (positive change) from baseline indicates improvement. |
| Change in Language Function: Semantic Fluency Test | Baseline, Week 12, Week 24 | Change from baseline in the number of animals named per minute on the Semantic Fluency Test, measuring verbal fluency and lexical access. Unabbreviated Scale Title: Semantic Fluency Test (Animal Naming) Scale Range: Minimum = 0, Maximum = no fixed upper limit (typical range in healthy adults: 12-25; in FTD patients: 0-15) \*Note: The test is scored as the number of unique, correct animal names produced within 60 seconds. While theoretically open-ended, practical scores rarely exceed 30-40.\* Interpretation: Higher scores indicate better verbal fluency and language function; an increase (positive change) from baseline indicates improvement. |
| Change in Neuropsychiatric Symptoms: NPI Score | Baseline, Week 12, Week 24 | Change from baseline in Neuropsychiatric Inventory (NPI) total score, assessing behavioral and psychiatric symptoms in dementia. Unabbreviated Scale Title: Neuropsychiatric Inventory (NPI) Scale Range: Minimum = 0, Maximum = 144 Note: The NPI assesses 12 domains (e.g., delusions, hallucinations, agitation, depression, anxiety, apathy, disinhibition, irritability, motor disturbances, sleep disturbances, appetite changes, and aberrant motor behavior). Each domain is scored as frequency (1-4) × severity (1-3), for a maximum of 12 per domain. Interpretation: Lower scores indicate fewer or less severe neuropsychiatric symptoms; a decrease (negative change) from baseline indicates improvement. |
| Change in Neuropsychiatric Symptoms: FBI Score | Baseline, Week 12, Week 24 | Change from baseline in Frontal Behavior Inventory (FBI) total score, measuring behavioral symptoms associated with frontotemporal dysfunction. Unabbreviated Scale Title: Frontal Behavior Inventory (FBI) Scale Range: Minimum = 0, Maximum = 72 \*Note: The FBI assesses 24 items (each scored 0-3), covering negative symptoms (e.g., apathy, indifference, loss of insight) and positive/disinhibited symptoms (e.g., impulsivity, perseveration, irritability, poor judgment).\* Interpretation: Lower scores indicate fewer or less severe frontal behavioral symptoms; a decrease (negative change) from baseline indicates improvement. |
| Change in Executive Function: FAB Score | Baseline, Week 12, Week 24 | Change from baseline in Frontal Assessment Battery (FAB) total score, assessing executive functions including conceptualization, mental flexibility, motor programming, sensitivity to interference, inhibitory control, and environmental autonomy. Unabbreviated Scale Title: Frontal Assessment Battery (FAB) Scale Range: Minimum = 0, Maximum = 18 Note: The FAB consists of 6 subtests, each scored from 0 to 3. Interpretation: Higher scores indicate better executive function; an increase (positive change) from baseline indicates improvement. |
| Change in Daily Function and Behavior: ADL Score | Baseline, Week 12, Week 24 | Change from baseline in Activities of Daily Living (ADL) scale total score, measuring the participant's ability to perform daily living activities. Unabbreviated Scale Title: Barthel Index of Activities of Daily Living (or specify the actual scale used, e.g., Katz Index of Independence in Activities of Daily Living, Lawton Instrumental Activities of Daily Living Scale) Scale Range (Barthel Index): Minimum = 0, Maximum = 100 Note: The Barthel Index assesses 10 items (e.g., feeding, bathing, grooming, dressing, bowel and bladder control, toilet use, transfers, mobility, stair climbing). Alternative ADL scales may have different ranges (e.g., Katz Index: 0-6). Interpretation: Lower scores indicate worse functional status (greater dependence); higher scores indicate better functional status (greater independence). Please confirm - the provided description states "Lower scores indicate better functional status," which is atypical for most ADL scales. Usually, higher scores = better fun |
Contacts
CONTACTChao Gao, MD，Ph.D
CONTACTShengdi Chen, MD, Ph.D
PRINCIPAL_INVESTIGATORShengdi Chen, MD, Ph.D
Department of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
Outcome results
None listed