Clinical Trial of Mesenchymal Stem Cells in the Treatment of Severe Acute Kidney Injury

A Single-center, Randomized, Placebo-controlled, Patient-blinded Study of Mesenchymal Stem Cells Therapy in Subjects With Severe Acute Kidney Injury Receiving Routine Therapy

Acute kidney injury(AKI) is a common, severe emergency case in clinics,especially severe AKI ,which is associated with higher morbidity and mortality. Effect of routine therapy is limited and mesenchymal stem cells (MSC)are considered a new therapy for treating severe acute kidney injury. Patients will be randomized to receive intravenous infusion of MSC, or placebo control. This trial is to investigate whether MSC can improve renal recovery and mortality of patients with AKI.

Study Overview

• Status: Not yet recruiting
• Conditions: Acute Kidney Injury; Mesenchymal Stem Cells
• Intervention / Treatment: Biological: Mesenchymal stem cells; Other: Saline

• Study Type: Interventional
• Enrollment (Anticipated): 80
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100853
      • Chinese PLA General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Have severe AKI defined as more than two-fold increase serum creatinine level compared with baseline within 48 hours and/or urinary output consistently<0.5 ml/kg/h over 12 hours
• Age between 18 and 65 years
• Willing or having a legally acceptable representative to give a written informed consent
• Able to comply with visit schedule and study procedures including post-hospitalization discharge follow-up

Exclusion Criteria:

• AKI due to post-renal outflow obstruction,glomerulonephritis,lupus nephritis, antineutrophil cytoplasmic antibody (ANCA) related nephritis, antiglomerular basement membrane disease, cryoglobulinemia, thrombotic microangiopathy, and AKI caused by purpura nephritis
• Pregnant or lactating woman
• Allergic person
• Organ transplant or hematopoietic stem cell transplant
• Patients with malignant tumors or those with a history of cancer
• Life expectancy is less than 3 months
• Known end-stage liver disease
• Uncontrollable infection
• Patients younger than 65 years old ,whose estimated glomerular filtration rate (eGFR) were less than 60
• Severe pulmonary dysfunction
• Severe cardiac dysfunction,left ventricular ejection fraction is less than 40%, or severe arrhythmia patients
• Hemodynamically unstable patients
• Organ failure affecting more than 2 non-renal organs
• Acute or chronic vasculitis of any cause
• History of chronic systemic infection of any cause
• The investigators believe that subjects may need to gradually increase the dose of vasopressor to achieve and / or maintain hemodynamic stability
• Systemic immunosuppressive therapy that has not been stabilized for greater than 4 months, or in the case of chronic corticosteroid therapy, a dose of >15 mg/day of prednisone or the equivalent within the past 30 days
• Platelet count <25,000/uL or other severe hematologic abnormalities, causing the subject to be at risk of death
• Patients need mechanical ventilation
• Participate in other clinical trials

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: Mesenchymal stem cells cohort	Biological: Mesenchymal stem cells; In experimental group, patients receive standard treatment and allogeneic human umbilical cord derived-mesenchymal stem cells (MSCs) is administered via intravenous infusion on day 0 and day 7
Placebo Comparator: Saline cohort	Other: Saline; In placebo control group, patients receive standard treatment and saline is administered via intravenous infusion on day 0 and day 7

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The difference in the renal function between the two groups (MSC treatment group vs placebo control group) within 28 days after receiving MSC/ placebo treatment	Compare the creatinine concentration between the two groups (MSC treatment group vs placebo control group) at 28 days after receiving MSC/ placebo treatment.	within 28 days after receiving MSC/ placebo treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival within 28 days after receiving MSC/ placebo treatment	Compare the overall survival rate between the two groups (MSC treatment group vs placebo control group) at 28 days after receiving MSC/ placebo treatment.	28 days
Overall survival within 3 months after receiving MSC/ placebo treatment	Compare the overall survival rate between the two groups (MSC treatment group vs placebo control group) at month 3 after receiving MSC/ placebo treatment.	3 months
Renal replacement therapy (RRT) dependent within 3 months after receiving MSC/ placebo treatment	Compare the rate of renal replacement therapy (RRT) dependence between the two groups (MSC treatment group vs placebo control group) at month 3 after receiving MSC/ placebo treatment.	3 months
Complete renal recovery within 3 months after receiving MSC/ placebo treatment	Compare the rate of complete renal recovery between the two groups (MSC treatment group vs placebo control group) at month 3 after receiving MSC/placebo treatment. We considered complete recovery as alive, free of RRT, and the SCR decreased to no more than 1.5 times of the baseline level.	3 months
Partial renal recovery within 3 months after receiving MSC/ placebo treatment	Compare the rate of partial renal recovery between the two groups (MSC treatment group vs placebo control group) at month 3 after receiving MSC/placebo treatment. Partial recovery refers to survival, free of RRT, and the SCR 1.5 times higher than the baseline level of creatinine.	3 months
ICU and hospitalization duration of stay among all AKI patients within 3 months after receiving MSC/ placebo treatment	Compare the days in ICU and hospital between the two groups (MSC treatment group vs placebo control group) at month 3 after receiving MSC/placebo treatment.	3 months
Adverse events within 3 months after receiving MSC/ placebo treatment	Compare the rate of adverse events between the two groups (MSC treatment group vs placebo control group) at month 3 after receiving MSC/placebo treatment.	3 months

Collaborators and Investigators

• Sponsor: Chinese PLA General Hospital

Publications and helpful links

General Publications

• Yang Y, Gao J, Wang S, Wang W, Zhu FL, Wang X, Liang S, Feng Z, Lin S, Zhang L, Chen X, Cai G. Efficacy of umbilical cord mesenchymal stem cell transfusion for the treatment of severe AKI: a protocol for a randomised controlled trial. BMJ Open. 2022 Feb 21;12(2):e047622. doi: 10.1136/bmjopen-2020-047622.

Study record dates

Study Major Dates

• Study Start (Anticipated): December 31, 2021
• Primary Completion (Anticipated): October 31, 2022
• Study Completion (Anticipated): December 31, 2022

Study Registration Dates

• First Submitted: December 9, 2019
• First Submitted That Met QC Criteria: December 9, 2019
• First Posted (Actual): December 11, 2019

Study Record Updates

• Last Update Posted (Actual): October 25, 2021
• Last Update Submitted That Met QC Criteria: October 19, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency; Wounds and Injuries; Acute Kidney Injury
• Other Study ID Numbers: MSC-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Sharing Time Frame: Data will be available beginning immediately following publication and ending 36 months following article publication.
• 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
• product manufactured in and exported from the U.S.: No