Evaluating the Safety and Efficacy of Autologous Adipose Tissue-derived Mesenchymal Stem Cell Transplantation on Proinflammatory Cytokines and Anti-inflammatory Cytokines on Ageing-related Low-grade Inflammation Patients.

Study Overview
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Brief Summary
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Single-group, open-label, phase I / II clinical trial: Evaluation of the safety of autologous adipose tissue-derived mesenchymal stem cell transplantation in inflammaging (Ageing-related low-grade inflammation) patients.

Detailed Description
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The proposed study is a single-group, open-label, phase I / II clinical trial in which the patients will be treated with two doses (100 million i.v) of autologous adipose tissue-derived mesenchymal stem cell transplantation. This study aims to evaluate the safety and efficiency of autologous adipose tissue-derived mesenchymal stem cell transplantation in inflammaging (Ageing-related low-grade inflammation) patients. The inflammaging-patients are who have cytokine increasing (IL6 and TNF alfa)

Official Title
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Single-group, Open-label, Phase I / II Clinical Trial: Evaluating the Safety and Efficacy of Autologous Adipose Tissue-derived Mesenchymal Stem Cell Transplantation on Proinflammatory Cytokines and Cytokines Balance in Inflammaging (Ageing-related Low-grade Inflammation) Patients.

Conditions
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Aging Problems, Aging, Chronic Inflammation

Intervention / Treatment
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* Biological: autologous adipose-derived mesenchymal stem cell transplantation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female patient, age 40 to 64 years. The inflammatory aging patient as defined in the protocol as TNF alpha or IL6 at the time of screening was higher than the 95% healthy percentile value declared by the test system manufacturer. Have at least 2 of the 3 following diseases: Diabetes type II Dyslipidemia Obesity [The diagnosis and determination of accompanying diseases (Diabetes, Dyslipidemia, Obesity) will be carried out according to the general guidance of the MOH Vietnam]. Patients are using stable drugs for co-infection (diabetes mellitus, dyslipidemia, obesity) stably in the past 3 months. Agree to participate in research and agree to comply with the research examination and evaluation process. Exclusion Criteria: Patients with a blood-clotting disorder or hemophilia Patients with severe heart failure Acute respiratory pathology at the time of screening Patients with cancer or other acute illness need treatment. Patients with a history of allergy to anesthetics, anesthesia, and antibiotics Patients are planning to participate in another clinical trial while participating in the study There are other conditions or circumstances in which it is difficult for researchers to ensure adherence to treatment in the judgment of researchers.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 64 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Interventional Model Description: Evaluating the Safety and Efficacy of Autologous Adipose Tissue-derived Mesenchymal Stem Cell Transplantation on Proinflammatory Cytokines and Anti-inflammatory Cytokines on Ageing-related Low-grade Inflammation Patients.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MSC transplantation<br>Transplant 100 million MSCs | Biological: autologous adipose-derived mesenchymal stem cell transplantation<br>* Transplant 100 million autologous adipose-derived mesenchymal stem cells at Day 0 and Day 90<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The safety and toleration of stem cell infusion | Assess the safety and tolerance of autologous adipose-derived mesenchymal stem cell transplantation in patients with inflammatory aging. During the entire duration of the study, the likelihood of adverse event occurrence and adverse event effects related or unrelated to stem cell infusion will be reported according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. | Study recruirement day 0 | 
| The safety and toleration of stem cell infusion | Assess the safety and tolerance of autologous adipose-derived mesenchymal stem cell transplantation in patients with inflammatory aging. During the entire duration of the study, the likelihood of adverse event occurrence and adverse event effects related or unrelated to stem cell infusion will be reported according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. | Day 90 | 
| The safety and toleration of stem cell infusion | Assess the safety and tolerance of autologous adipose-derived mesenchymal stem cell transplantation in patients with inflammatory aging. During the entire duration of the study, the likelihood of adverse event occurrence and adverse event effects related or unrelated to stem cell infusion will be reported according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. | Study endpoint at day 180 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The change of proinflammatory cytokines after stem cell transplantation in patients | The measurement of proinflammatory cytokines concentration in patients peripheral blood such as IL-1α (pg/ml), IL-1β (pg/ml), TNF-α (pg/ml), TNF-β (pg/ml), IL-6 (pg/ml), IL-11 (pg/ml), IL-18 (pg/ml), IFN-γ (pg/ml) at day 0, 90, and 180 after stem cell infusion. During the study period, the variation of cytokine levels in individual patients revealed the results. | Day 0, Day 90 and Day 180 | 
| The change of anti-inflammatory cytokines after stem cell transplantation in patients | At day 0, 90, and 180 after stem cell infusion, the concentration of anti-inflammatory cytokines such as IL - 4 (pg/ml), IL-10 (pg/ml), EGF (pg/ml), and MCP-1 (pg/ml) in the peripheral blood of patients is measured. During the study period, the variation of cytokine levels in individual patients revealed the results. | Day 0, Day 90 and Day 180 | 
| The influence of stem cell transplantation on thechange of the ratio of pro-inflammatory to anti-inflammatory cytokines | The ratio of pro-inflammatory cytokines to anti-inflammatory cytokines will be used to assess the inflammation balance. The ratios from baseline were compared to three and six months after stem cell infusion such as IL-4/IL-10, IL-1/IL-10, IL-6/IL-10, and IL-1/EGF will be reported. | Day 0, Day 90 and Day 180 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ageing-related low-grade inflammation;, inflammaging;, aging