MSC-Exosome Therapy for Frontotemporal Dementia
A Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate the Safety and Efficacy of Umbilical Cord Mesenchymal Stem Cell-Derived Exosomes Via Intranasal Administration in Patients With Frontotemporal Dementia
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).
調査の概要
状態
条件
研究の種類
入学 (推定)
段階
- フェーズ2
- フェーズ 1
連絡先と場所
研究連絡先
- 名前：Chao Gao, MD，Ph.D
- 電話番号：+8618217590273
- メール：anshangaochao@163.com
研究連絡先のバックアップ
- 名前：Shengdi Chen, MD, Ph.D
- 電話番号：+8613818018166
- メール：chensd@rjh.com.cn
参加基準
適格基準
就学可能な年齢
- 大人
- 高齢者
健康ボランティアの受け入れ
説明
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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.
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：ランダム化
- 介入モデル：並列代入
- マスキング：トリプル
武器と介入
参加者グループ / アーム |
介入・治療 |
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プラセボコンパレーター：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.
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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.
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実験的：Low-Dose Exosome Group
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.
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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.
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実験的：High-Dose MSC-Exosome
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 without dose-limiting toxicity or serious adverse events.
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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.
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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
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Clinical Efficacy: Change in CDR plus NACC FTLD Score
時間枠：Baseline and Week 24
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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
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Safety and Tolerability: Incidence of Adverse Events
時間枠：Baseline through Week 24 (end of treatment)
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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.
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Baseline through Week 24 (end of treatment)
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
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Change in Global Cognition: MMSE Score
時間枠：Baseline, Week 12, Week 24
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Change from baseline in Mini-Mental State Examination (MMSE) total score.
Range: 0-30, with higher scores indicating better cognitive function.
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Baseline, Week 12, Week 24
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Change in Global Cognition: MoCA Score
時間枠：Baseline, Week 12, Week 24
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Change from baseline in Montreal Cognitive Assessment (MoCA) Basic Version total score.
Range: 0-30, with higher scores indicating better cognitive function.
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Baseline, Week 12, Week 24
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Change in Language Function: BNT Score
時間枠：Baseline, Week 12, Week 24
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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. |
Baseline, Week 12, Week 24
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Change in Language Function: Semantic Fluency Test
時間枠：Baseline, Week 12, Week 24
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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. |
Baseline, Week 12, Week 24
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Change in Neuropsychiatric Symptoms: NPI Score
時間枠：Baseline, Week 12, Week 24
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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. |
Baseline, Week 12, Week 24
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Change in Neuropsychiatric Symptoms: FBI Score
時間枠：Baseline, Week 12, Week 24
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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. |
Baseline, Week 12, Week 24
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Change in Executive Function: FAB Score
時間枠：Baseline, Week 12, Week 24
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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. |
Baseline, Week 12, Week 24
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Change in Daily Function and Behavior: ADL Score
時間枠：Baseline, Week 12, Week 24
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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 |
Baseline, Week 12, Week 24
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その他の成果指標
結果測定 |
メジャーの説明 |
時間枠 |
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Change in Brain Structure: Regional Brain Volume
時間枠：Baseline，and Week 24
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Change from baseline in regional brain volume, assessed by structural magnetic resonance imaging (MRI), to evaluate the effect of intranasal exosome treatment on brain structure in FTD patients. Units of Measure: Cubic millimeters (mm³) or percentage change from baseline in specific regions of interest (e.g., frontal lobe, temporal lobe, hippocampus) Interpretation: Specific regional volume changes will be analyzed exploratory. Direction of improvement is not predefined for this exploratory outcome. |
Baseline，and Week 24
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Change in Brain Function: Resting-State Functional Connectivity
時間枠：Baseline and Week 24
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Change from baseline in resting-state functional connectivity, assessed by functional magnetic resonance imaging (fMRI), to evaluate the effect of intranasal exosome treatment on brain function in FTD patients. Units of Measure: Correlation coefficient (z-scored or Fisher-transformed correlation values between predefined brain networks or regions of interest) Interpretation: Changes in functional connectivity will be analyzed exploratory. Direction of improvement is not predefined for this exploratory outcome. |
Baseline and Week 24
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Change in Plasma Biomarker: Neurofilament Light Chain (NfL)
時間枠：Baseline，Week 24
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Exploratory outcome: Change from baseline in plasma levels of neurofilament light chain (NfL), a biomarker of axonal injury associated with frontotemporal dementia pathophysiology. Units of Measure: Picograms per milliliter (pg/mL) Interpretation: Higher levels indicate greater axonal injury; a decrease (negative change) from baseline may suggest improvement (reduced neuronal damage). This is an exploratory outcome. |
Baseline，Week 24
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Change in Plasma Biomarker: Tau Proteins
時間枠：Baseline and Week 24
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Exploratory outcome: Change from baseline in plasma levels of tau proteins (e.g., total tau, phosphorylated tau), biomarkers associated with frontotemporal dementia pathophysiology. Units of Measure: Picograms per milliliter (pg/mL) - please confirm based on assay used Interpretation: Higher levels may indicate greater neurodegeneration; a decrease (negative change) from baseline may suggest improvement. This is an exploratory outcome. |
Baseline and Week 24
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協力者と研究者
スポンサー
協力者
捜査官
- 主任研究者：Shengdi Chen, MD, Ph.D、Department of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
研究記録日
主要日程の研究
研究開始 (推定)
一次修了 (推定)
研究の完了 (推定)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
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