Exosome of Mesenchymal Stem Cells for Multiple Organ Dysfuntion Syndrome After Surgical Repaire of Acute Type A Aortic Dissection

Exosome of Mesenchymal Stem Cells for Multiple Organ Dysfuntion Syndrome After Surgical Repaire of Acute Type A Aortic Dissection: a Pilot Study

Multiple organ dysfunction syndrome (MODS) after surgical repaired for acute type A aortic dissection (ATAAD) is a life-threatening condition. In this study, patients who undergoing surgical repaired of ATAAD immediately or presenting sever MODS after surgical repaired of acute type A aortic dissection will be treated with umbilical cord-derived mesenchymal stem cell.

Study Overview

• Status: Not yet recruiting
• Conditions: Multiple Organ Failure
• Intervention / Treatment: Biological: Exosome of MSC

Detailed Description

Multiple organ dysfunction syndrome (MODS) are common debilitating complications after surgical repaired for ATAAD. MODS is one of the chief causes of post-operative death for acute type A aortic dissection (ATAAD) patients, and it was reported that MODS accounted for more than half of the death after surgery for ATAAD. Despite recent advance in surgical technique, mortality rate remains high in such critical care conditions. In animal models, studies have demonstrated the beneficial effects of MSCs with respect to ischemia-reperfusion injury of heart, lungs, kidney, brains and livers. Several pilot studies have provided evidence that MSC may be effective in treating critically ill patients with traumatic brain injury, acute renal failure, or acute respiratory distress syndrome. There is increasing evidence that MSCs function in a paracrine manner. Exosomes have been reported to activate signaling pathways by binding to receptors. Compared with mesenchymal stem cells, exosomes are more stable and storable and no risk of aneuploidy. The possibility of immune rejection after allogeneic administration of exosomes is lower and can provide alternative treatment for a variety of diseases.

The trial contains two parts:

Part one (prevention scheme):to explore the safety and efficacy of exosome of MSC, the investigators will recruit patients who are diagnosed with ATAAD, and 15 participants will be administrated intravenously with exosome of MSC immediately after ascending aortic replacement combined with open placement of triple branched stent graft while other 15 not. Then the investigators will monitor participants' MODS related biochemical indexes, sequential organ failure assessment (SOFA) scores, comparing to those don't be treated with exosome of MSC.

Phase two (treatment scheme): for patients presenting severe MODS (SOFA score≥10) after ascending aortic replacement combined with open placement of triple-branched stent graft, the investigators will randomly use exosome of MSC to 15 of participants while other 15 not. Then the investigators will monitor participants' MODS related biochemical indexes, SOFA scores, comparing to those don't be treated with MSC. The dosage of the exosome of MSC was determined on the basis of the previous clinical studies, which is 180mg once a time and administrated intravenously.

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Yi-Kun Jiang; Phone Number: 86-14759926068; Email: 869582567@qq.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Part 1:

  • Patients who are diagnosed with ATAAD and received emergency surgery with ascending aortic replacement combined with open placement of triple-branched stent graft
  • elder than 60 years old
  • Preoperative PaO2/FiO2 ≥ 400mmHg, platelets ≥ 150*109/L, bilirubin≥ 20μmol/L, no hypotension (without vasoactive drugs), Glasgow Coma Score Scale = 15, creatine ≥110μmol/L

Part 2:

• Patients who are diagnosed with ATAAD and received emergency surgery with ascending aortic replacement combined with open placement of triple-branched stent graft
• Patients who have failure of at least 2 organs
• Patients who meet the criteria as below:

sequential organ failure assessment score (SOFA) ≥ 10

Exclusion Criteria:

• • uncontrollable underlying disease life expectancy of less than 4 days history of long-term corticosteroid use during the past 6 months.

  • The pre-operative computer tomography angiography(CTA) demonstrate the visceral arteries are involved
  • pre-existing severe disease of any major organs

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: The exosome of MSC arm; Exosome of MSC at a dose of 150mg will be given intravenously to Patients in the exosome of MSC arm once a day for 14 times.	Biological: Exosome of MSC; Exosome of MSC at a dose of 150mg will be given intravenously to patients once a day for 14 times.
No Intervention: The control arm; Patients in the control arm will not be given exosome of MSC.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
survival after intervention	comparing survival ratio in hospital(6 months post-intervention) between groups.	Up to 6 month
sequential organ failure assessment score	Compare the change of sequential organ failure assessment score between groups. Scores ranged from 0 to 24. The higher the score, the worse the prognosis.	Up to 6 months
interleukin-6	Compare the change of concentration of interleukin( IL)-6 between groups.	Early 3 days
The number of allergic reactions	Allergic reactions are mostly manifested as skin flushing, rash and itching. Severe allergic reactions such as chills, high fever and anaphylactic shock are rare.	Up to 6 months
The number of people who get cancer	The number of people diagnosed with cancer after treatment	Up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the effects on kidney function	the therapeutic effects in the improvement of kidney function, as indicated by Scr level.	Up to 6 months
the effects on liver function	the therapeutic effects in the improvement of liver function, as indicated by bilirubin levels.	Up to 6 months
the effects on lung function	the therapeutic effects in the improvement of lung function, as indicated by oxygenation index.	Up to 6 months
the effects on coagulation function	the therapeutic effects in the improvement of coagulation function, as indicated by blood platelet count.	Up to 6 months
the effects on central nervous system	The Glasgow coma scale has a maximum score of 15 and a minimum score of 3, indicating consciousness. 12-14 was classified as mild consciousness disorder; 9-11 was classified as moderate disturbance of consciousness; A score below 8 is coma; The lower the score, the greater the disturbance of consciousness.	Up to 6 months

Collaborators and Investigators

• Sponsor: Fujian Medical University
• Investigators: Principal Investigator: Liang-wan Chen, M.D, Union Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): September 1, 2020
• Primary Completion (Anticipated): September 1, 2021
• Study Completion (Anticipated): September 1, 2030

Study Registration Dates

• First Submitted: April 19, 2020
• First Submitted That Met QC Criteria: April 19, 2020
• First Posted (Actual): April 22, 2020

Study Record Updates

• Last Update Posted (Actual): May 6, 2020
• Last Update Submitted That Met QC Criteria: May 5, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Shock; Aneurysm; Aneurysm, Dissecting; Multiple Organ Failure
• Other Study ID Numbers: 2020005

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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