the Safety and the Efficacy Evaluation of Allogenic Adipose MSC-Exos in Patients With Alzheimer's Disease

Open-Label, Single-Center, Phase I/Ⅱ Clinical Trial to Evaluate the Safety and the Efficacy of Exosomes Derived From Allogenic Adipose Mesenchymal Stem Cells in Patients With Mild to Moderate Dementia Due to Alzheimer's Disease

Evaluate the Safety and Efficacy of Exosomes Derived from Allogenic Adipose Mesenchymal Stem Cells（MSCs-Exos）in Subjects with Alzheimer's disease.

Study Overview

• Status: Unknown
• Conditions: Alzheimer Disease
• Intervention / Treatment: Biological: low dosage MSCs-Exos administrated for nasal drip; Biological: mild dosage MSCs-Exos administrated for nasal drip; Biological: high dosage MSCs-Exos administrated for nasal drip

Detailed Description

To date, the main pathological characteristics of AD patients are the accumulation of β-amyloid (Aβ) into senile plaques, the abnormal aggregation of intracellular Tau protein to form neuron fiber tangles (NFT) and neuron death. There are still no effective treatments to prevent, halt, or reverse Alzheimer's disease.

Exosomes are naturally occurring nanosized vesicles and comprised of natural lipid bilayers with the abundance of adhesive proteins that readily interact with cellular membranes. These vesicles have a content that includes cytokines and growth factors, signaling lipids, mRNAs, and regulatory miRNAs. Exosomes are involved in cell-to-cell communication, cell signaling, and altering cell or tissue metabolism at short or long distances in the body, and can influence tissue responses to injury, infection, and disease.

The purpose of this single center, open label, phase I/Ⅱ clinical trial, therefore, is to explore the safety and efficacy of the exosomes derived from allogenic adipose mesenchymal stem cells (MSCs-Exos) in the treatment of mild to moderate dementia due to Alzheimer's Disease.

• Study Type: Interventional
• Enrollment (Anticipated): 9
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200000
      • Recruiting
      • Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine
      • Contact: Xinyi Xie, MD; Phone Number: 18616817612; Email: Xiexy0619@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Subjects themselves and their legal representatives (or their immediate family members) voluntarily received the treatment and signed the consent form before this study;
2. Age ≧ 50 years, males and females;
3. Subjects diagnosed with Patients with mild or moderate Alzheimer's disease, based on the NIA/AA(2011).
4. The Mini-Mental Status Examination (MMSE) score was 10-24 (inclusive);
5. Modified Hachinski Ischemic Scale (MHIS) score was ≦ 4;
6. Suspension of cognitive-enhancing drugs and marketed therapeutic drugs such as ginkgo, high-dose vitamin E, lecithin, estrogen, non-steroidal anti-inflammatory drugs (NSAIDs), Donepezil, Memantine, etc ;
7. Based on medical history, physical examination, vital signs, laboratory tests and 12-lead electrocardiogram (ECG) results, subjects are generally in good condition;
8. Subjects can walk independently or receive outpatient follow-up with assistive devices (wheelchairs, walkers or crutches), while the subject's vision and hearing (allowing glasses and / or hearing aids) do not affect the follow-up procedure;
9. The subject has an identified and reliable caregiver who must also meet the following conditions:

(1) In the hospital, caregiver can independently read and understand relevant research documents, and can do necessary communication with the investigator; (2) Caregiver can follow clinical research procedures and ensure that accurate information about the status of the subject can be provided during the study; (3) Caregiver live with the subject; or take care of the subject no less than 3 days a week and no less than 2 hours a day; 10. Female subjects with fertility (including women of childbearing age and women less than 1 year after menopause) were required to take effective contraception throughout the study. At the same time, urine pregnancy tests were negative during screening.

Exclusion Criteria:

1. The subjects with more serious allergic constitution;
2. Received allogeneic mesenchymal progenitor cell therapy or its derived exosomes;
3. Laboratory test (any item meets): neutrophil absolute number < 1.0 × 109 / L, platelet count < 100 × 109 / L, serum albumin < 30g / L, serum creatinine > upper limit of normal value range, total bilirubin, alanine aminotransferase, aspartate aminotransferase > upper limit of 2 times of normal value range;
4. The subject has serious and poorly controlled concomitant diseases, such as (but not limited to) cardiovascular, cerebrovascular, liver, kidney, lung, endocrine and other system diseases;
5. Severe Alzheimer's Disease;
6. Severe depression;
7. The subjects suffered from Parkinson's disease, multiple cerebral infarction, vascular dementia, Huntington's disease, hydrocephalus, progressive supranuclear paralysis, multiple sclerosis, epilepsy, mental retardation or major history of brain injury (with or without persistent neurological impairment) or known brain structural abnormalities;
8. The subject has an history malignant tumor；
9. The subject has severe generalized infectious diseases in the 3 months prior to this trial.;
10. The subject has contraindication of MRI, included but not only: the subject installed heart pacemaker, defibrillator, heart bracket, heart valve prosthesis, metal clip after aneurysm surgery, drug infusion device implanted in vivo, any electronic device implanted in the body (nerve stimulator, bone growth stimulator) endovascular coil, strainer, ECG monitor, metal suture, shrapnel or sand of body, plate fixation and steel nail after fracture surgery, artificial cochlea, middle ear shift plant, metallic intraocular foreign body etc; the subject is a claustrophobia, critical ill patient and so on.
11. The subject tests positive for: HIV, HBV, HCV and treponema pallidum;
12. The subject has history of alcoholism, drug abuse, or mental illness in the 10 years prior to this trial.
13. The subject has participated in any other clinical trial in the 6 months prior to this trial;
14. The female subjects are pregnant, lactating or pregnant in the past half a year;
15. The subject has any other unsuitable condition (such as factors reducing the follow-up compliance) to be determined by the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MSCs-Exos Dosage 1; MSCs-Exos. low-dose group	Biological: low dosage MSCs-Exos administrated for nasal drip; Dosage：5μg MSCs-Exos,Total volume： 1ml Frequency：Twice a week Duration：12 weeks
Experimental: MSCs-Exos Dosage 2; MSCs-Exos mid-dose group	Biological: mild dosage MSCs-Exos administrated for nasal drip; Dosage：10μg MSCs-Exos,Total volume： 1ml Frequency：Twice a week Duration：12 weeks
Experimental: MSCs-Exos Dosage 3; MSCs-Exos high-dose group	Biological: high dosage MSCs-Exos administrated for nasal drip; Dosage：20μg MSCs-Exos,Total volume： 1ml Frequency：Twice a week Duration：12 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of participants with treatment-related abnormal laboratory values of Liver or kidney function	12 weeks
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cognitive function	ADAS-cog (Alzheimer 's disease assessment scale-cognitive section) consists of 12 items. Maximum value is 70 and higher score means a worse congnitive condition.	baseline
Cognitive function	ADAS-cog (Alzheimer 's disease assessment scale-cognitive section) consists of 12 items. Maximum value is 70 and higher score means a worse congnitive condition.	12 weeks
Cognitive function	ADAS-cog (Alzheimer 's disease assessment scale-cognitive section) consists of 12 items. Maximum value is 70 and higher score means a worse congnitive condition.	24 weeks
Cognitive function	ADAS-cog (Alzheimer 's disease assessment scale-cognitive section) consists of 12 items. Maximum value is 70 and higher score means a worse congnitive condition.	36 weeks
Cognitive function	ADAS-cog (Alzheimer 's disease assessment scale-cognitive section) consists of 12 items. Maximum value is 70 and higher score means a worse congnitive condition.	48 weeks
Quality of life evaluation	Scores of ADCS-ADL (Alzheimer's Disease Cooperative Study Activities of Daily Living) range from 0 to 54 and higher score means a better life quality.	baseline
Quality of life evaluation	Scores of ADCS-ADL (Alzheimer's Disease Cooperative Study Activities of Daily Living) range from 0 to 54 and higher score means a better life quality.	12 weeks
Quality of life evaluation	Scores of ADCS-ADL (Alzheimer's Disease Cooperative Study Activities of Daily Living) range from 0 to 54 and higher score means a better life quality.	24 weeks
Quality of life evaluation	Scores of ADCS-ADL (Alzheimer's Disease Cooperative Study Activities of Daily Living) range from 0 to 54 and higher score means a better life quality.	36 weeks
Quality of life evaluation	Scores of ADCS-ADL (Alzheimer's Disease Cooperative Study Activities of Daily Living) range from 0 to 54 and higher score means a better life quality.	48 weeks
MRI Neuroimaging	Evaluation of MRI（Magnetic Resonance Imaging)	baseline
MRI Neuroimaging	Evaluation of MRI（Magnetic Resonance Imaging)	48 weeks
PET-CT Neuroimaging	Evaluation of and PET-CT（Positron Emission Computed Tomography- Computed Tomography)	baseline
PET-CT Neuroimaging	Evaluation of and PET-CT（Positron Emission Computed Tomography- Computed Tomography)	48 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes of AD biomarkers	Changes of Aβ in serum and cerebrospinal fluid will be tested at baseline and 48 weeks	baseline and 48 weeks

Collaborators and Investigators

• Sponsor: Ruijin Hospital
• Collaborators: Cellular Biomedicine Group Ltd.
• Investigators: Principal Investigator: Gang Wang, MD,PhD, Ruijin Hospital; Principal Investigator: Xiaoling Gao, PhD, Shanghai Jiao Tong University School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2020
• Primary Completion (Anticipated): August 1, 2021
• Study Completion (Anticipated): August 1, 2022

Study Registration Dates

• First Submitted: April 28, 2020
• First Submitted That Met QC Criteria: May 14, 2020
• First Posted (Actual): May 15, 2020

Study Record Updates

• Last Update Posted (Actual): June 25, 2021
• Last Update Submitted That Met QC Criteria: June 23, 2021
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease
• Other Study ID Numbers: CBMG-AD-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Sharing Supporting Information Type: Study Protocol

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No