Mesenchymal Stem Cells to Treat Type 2 Diabetes (UC-MSCs)

• ClinicalTrials.gov Identifier: NCT02302599
• Recruitment Status: Completed
• First Posted: November 27, 2014
• Last Update Posted: February 3, 2021
• Sponsor: Chinese PLA General Hospital
• Information provided by (Responsible Party): Yiming Mu, Chinese PLA General Hospital

Tracking Information

• First Submitted Date: November 12, 2014
• First Posted Date: November 27, 2014
• Last Update Posted Date: February 3, 2021
• Actual Study Start Date: January 2013
• Actual Primary Completion Date: December 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 29, 2020)

The efficacy of umbilical cord mesenchymal stem cells in Chinese adults with T2D [ Time Frame: 48 weeks from baseline ]

proportion of patients with HbA1c <7.0% and daily insulin reduction ≥50% from baseline to 48 weeks

• Original Primary Outcome Measures (submitted: November 26, 2014): Change in MSCs Level From Baseline to Week 48 From Baseline [ Time Frame: 48 weeks ]

Current Secondary Outcome Measures (submitted: October 29, 2020)

• Other efficacy parameter of umbilical-cord mesenchymal stem cells in Chinese adults with T2D [ Time Frame: 48 weeks from baseline ]
  Changes of insulin requirement, HbA1c and proportion of patients reaching the HbA1c target (<7.0%)
• Other efficacy parameter of umbilical-cord mesenchymal stem cells in Chinese adults with T2D [ Time Frame: 48 weeks from baseline ]
  Change of islet β cell function and insulin resistance
• safety parameter of umbilical-cord mesenchymal stem cells in Chinese adults with T2D [ Time Frame: 48 weeks from baseline ]
  Fever, pruritus, nausea and vomiting, anaphylactic shock, phlebitis，tumor formation, infection, impaired liver and kidney function.

• Original Secondary Outcome Measures (submitted: November 26, 2014): Change From Baseline in Fasting Glucose Over Time [ Time Frame: 48 weeks from baseline ]
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures (submitted: November 26, 2014): Response Rates for Reduction in Fasting Glucose of ≥20 mg/dl, a Reduction in HbA1c of ≥0.5%, and a Reduction in HbA1c of ≥0.8% [ Time Frame: 48 weeks ]

Descriptive Information

• Brief Title: Mesenchymal Stem Cells to Treat Type 2 Diabetes
• Official Title: Efficacy and Safety of Umbilical-cord Mesenchymal Stem Cells in Chinese Adults With Type 2 Diabetes: a Single Center, Double-blind, Randomized, Placebo-controlled Trial
• Brief Summary: Umbilical cord mesenchymal stem cells indicate the therapeutic effects and safety on type 2 diabetes by characteristics of secretion and immune Immunomodulation.
• Detailed Description: Umbilical cord mesenchymal stem cells can improve insulin resistance of the target tissues, reduce the islet progressive damage, ease or regenerate of the islet beta cells and improve hyperglycemic state of diabetes by secreting a variety of cytokines. It can induce damaged alpha cells differentiate into beta cells in the islet transformation to realize the islet beta cells in situ regeneration by improving microenvironment of islet beta cells. Umbilical cord mesenchymal stem cells also have immunosuppressive effect, it can promote islet cell repair and regeneration by the inhibition of T cell mediated immune response to beta cells.
• Study Type: Interventional
• Study Phase: Phase 2

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

UC-MSCs (1.5×106/kg) or the same volume of placebo (suspension liquid without UC-MSCs)

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:

All investigators and participants were masked to treatment allocation. The independent data monitoring committee and the statisticians supporting the committee's activities were the only people with access to unblinded data.

Primary Purpose: Treatment

Condition

• Type 2 Diabetes
• Mesenchymal Stem Cells

Intervention

• Biological: Umbilical cord mesenchymal stem cells
  Infusion treatment
• Biological: Controlled suspension liquid
  Infusion treatment

Study Arms

• Experimental: Umbilical cord mesenchymal stem cells
  Patients receive Umbilical cord mesenchymal stem cells intravenous infusion for three times with an interval of 4 weeks in the absence of disease progression or unacceptable toxicity
  Intervention: Biological: Umbilical cord mesenchymal stem cells
• Experimental: Controlled suspension liquid
  Patients receive Controlled suspension liquid
  Intervention: Biological: Controlled suspension liquid

Publications *

• Hao H, Liu J, Shen J, Zhao Y, Liu H, Hou Q, Tong C, Ti D, Dong L, Cheng Y, Mu Y, Liu J, Fu X, Han W. Multiple intravenous infusions of bone marrow mesenchymal stem cells reverse hyperglycemia in experimental type 2 diabetes rats. Biochem Biophys Res Commun. 2013 Jul 5;436(3):418-23. doi: 10.1016/j.bbrc.2013.05.117. Epub 2013 Jun 11.
• Wang XL, Lu JM, Pan CY, Mu YM, Dou JT, Ba JM. [Characteristics of the daily blood glucose profiles of impaired glucose tolerance and type 2 diabetes mellitus subjects by continuous glucose monitoring system]. Zhonghua Yi Xue Za Zhi. 2006 Mar 14;86(10):674-7. Chinese.
• Si Y, Zhao Y, Hao H, Liu J, Guo Y, Mu Y, Shen J, Cheng Y, Fu X, Han W. Infusion of mesenchymal stem cells ameliorates hyperglycemia in type 2 diabetic rats: identification of a novel role in improving insulin sensitivity. Diabetes. 2012 Jun;61(6):1616-25. doi: 10.2337/db11-1141.
• Zang L, Li Y, Hao H, Liu J, Cheng Y, Li B, Yin Y, Zhang Q, Gao F, Wang H, Gu S, Li J, Lin F, Zhu Y, Tian G, Chen Y, Gu W, Du J, Chen K, Guo Q, Yang G, Pei Y, Yan W, Wang X, Meng J, Zhang S, Ba J, Lyu Z, Dou J, Han W, Mu Y. Efficacy and safety of umbilical cord-derived mesenchymal stem cells in Chinese adults with type 2 diabetes: a single-center, double-blinded, randomized, placebo-controlled phase II trial. Stem Cell Res Ther. 2022 May 3;13(1):180. doi: 10.1186/s13287-022-02848-6.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: February 1, 2021): 103
• Original Estimated Enrollment (submitted: November 26, 2014): 200
• Actual Study Completion Date: December 2020
• Actual Primary Completion Date: December 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. 20 ≤ age ≤ 65 years;
2. Duration of type 2 diabetes ≤20 years;
3. 24.0 kg/m2 ≤ BMI ≤40.0 kg/m2;
4. Stable exogenous insulin dose between 0.5-1.0 U/Kg/Day with or without oral hypoglycemic agents (Dipeptidyl peptidase-4 (DPP-4) inhibitor, Glucagon like peptide 1 receptor (GLP-1R) agonist and Sodium-glucose co-transporter 2 (SGLT-2) inhibitor excluded) for at least 3 months;
5. 7.0% ≤ HbA1c ≤ 12.0%;
6. Fasting C-peptide ≥ 1ng/ml;
7. Willingness to participate in the trial.

Exclusion Criteria:

1. Patients with ketonuria, tumor, serum creatinine level more than 175μmol/L, myocardial infarction in the previous year, current angina or heart failure, more than one major vascular event, retinopathy requiring laser treatment, malignant hypertension, uncorrected endocrine disorder, occupations precluding insulin therapy;
2. Severe concurrent illness limiting life expectancy, inadequate understanding of the study protocol, drug abuse, pregnant willing and allergic constitution.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 20 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: China

Administrative Information

• NCT Number: NCT02302599
• Other Study ID Numbers: CHIN-PLAGH-ST-003
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Yiming Mu, Chinese PLA General Hospital
• Original Responsible Party: Same as current
• Current Study Sponsor: Chinese PLA General Hospital
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: weidong HAN; Chinese PLA General Hospital
• Principal Investigator: yiming MU; Chinese PLA General Hospital

• PRS Account: Chinese PLA General Hospital
• Verification Date: February 2021