Umbilical Mesenchymal Stem Cells and Mononuclear Cells Infusion in Type 1 Diabetes Mellitus

Umbilical Mesenchymal Stem Cells and Mononuclear Cells Infusion in Type 1 Diabetes Mellitus: A Randomized Controlled Open-label Study

Umbilical mesenchymal stem cells (UC-MSCs) infusion is supposed be a promising regeneration therapy with mild side effect as indicated by large quantities of animal experiments and some clinical trials. There are few UC-MSCs clinical trials with regard to diabetes mellitus. The investigators hypothesize that infusion of USC-MSCs may provide multiple signals for beta-cell regeneration and even re-differentiate into local tissues in diabetes mellitus patients, resulting in improvement of diabetic control, of which the effect may be promoted by concomitant infusion of bone marrow mononuclear cells and maximized by intra-arterial pancreatic infusion through angiography.

Study Overview

• Status: Unknown
• Conditions: Type 1 Diabetes Mellitus
• Intervention / Treatment: Biological: Umbilical mesenchymal stem cell (UC-MSCs) infusion; Drug: traditional therapy

• Study Type: Interventional
• Enrollment (Actual): 44
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Fujian
    • Fuzhou, Fujian, China, 350025
      • Fuzhou General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male and female patients age 18 to 65 years of age.
• Ability to provide written informed consent.
• Mentally stable and able to comply with the procedures of the study protocol.
• Clinical history compatible with type 1 diabetes (T1DM) as defined by the Expert Committee on the Diagnosis and classification of Diabetes Mellitus
• Onset of T1DM disease at ≤ 35 years of age.
• T1DM duration ≥ 2 and ≤ 20 years at the time of enrollment.
• Basal C-peptide ≤ 0.3 ng/mL
• HbA1c ≥ 7.5 at time of enrollment.

Exclusion Criteria:

• BMI >35 kg/m^2.
• Insulin requirements of > 100 U/day.
• C-reactive protein (hs-CRP) >3.00ng/ml
• Uncontrolled blood Pressure: SBP >160 mmHg or DBP >100 mmHg at the time of enrollment.
• Evidence of renal dysfunction, serum creatinine > 1.5 mg/dl (males) and 1.4 mg/dl (females).
• Proteinuria > 300 mg/day
• Evidence of cardiovascular disease, existing congestive cardiac failure on physical exam and/or acute coronary syndrome in past 6 months.
• For female participants: Positive pregnancy test, presently breast-feeding, or unwillingness to use effective contraceptive measures for the duration of the study. For male participants: intent to procreate 3 months before or after the intervention or unwillingness to use effective measures of contraception. Oral contraceptives, Norplant®, Depo-Provera®, and barrier devices with spermicide are acceptable contraceptive methods; condoms used alone are not acceptable
• Active infection including hepatitis C, HIV, or TB as determined by a positive skin test or clinical presentation, or under treatment for suspected TB. Positive tests are acceptable only if associated with a history of previous vaccination in the absence of any sign of active infection. Positive tests are otherwise not acceptable, even in the absence of any active infection at the time of evaluation
• Known active alcohol or substance abuse including cigarette/cigar smoking
• Baseline Hemoglobin below the lower limits of normal at the local laboratory; lymphopenia (<1,000/L), neutropenia (<1,500/L), or thrombocytopenia (platelets <100,000/L).
• A history of Factor V deficiency or other coagulopathy defined by INR >1.5, PTT >40, PT >15.
• Any coagulopathy or medical condition requiring long-term anticoagulant therapy (e.g., warfarin) after transplantation (low-dose aspirin treatment is allowed) or patients with an INR >1.5.
• Acute or chronic pancreatitis.
• Symptomatic peptic ulcer disease.
• Hyperlipidemia despite medical therapy (fasting LDL cholesterol >130 mg/dl, treated or untreated; and/or fasting triglycerides > 200 mg/dl).
• Receiving treatment for a medical condition requiring chronic use of systemic steroids.
• Symptomatic cholecystolithiasis.
• Use of any investigational agents within 4 weeks of enrollment.
• Admission to hospital for any reason in the 14 days prior to enrollment (signing consent).
• Presence of active proliferative diabetic retinopathy or macular edema
• Any malignancy
• Abnormal liver function >1.5 x ULN
• Abdominal aortic aneurysm
• History of cerebro-vascular accident
• Any patient with acute or subacute decompensation from diabetes
• Any acute or chronic infectious condition that in the criteria of the investigator would be a risk for the patient.
• Subjects with hypoproteinemia, cachexia or terminal states
• Subjects with history of anorexia/bulimia
• Subjects with respiratory insufficiency
• Any medical condition that, in the opinion of the investigator, will interfere with the safe completion of the trial.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Stem Cell Infusion	Biological: Umbilical mesenchymal stem cell (UC-MSCs) infusion; 1×10^6/kg UC-MSCs is infused through pancreatic artery along with mononuclear cells by interventional therapy and another same dose of UC-MSCs is administered one week post-intervention.
Active Comparator: traditional therapy control	Drug: traditional therapy; exogenous insulin injection daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
c-peptide area under the curve during OGTT	1 year

Secondary Outcome Measures

Outcome Measure	Time Frame
The reduction in fasting blood glucose (FBG)	1 year
The increase in basal C-peptide	1 year
The incidence and severity of adverse events related to the stem cell infusion procedure	1 year
The reduction in exogenous insulin requirements	1 year
Decrease in HbA1c	1 year
insulin area under the curve during OGTT	1 year

Collaborators and Investigators

• Sponsor: Fuzhou General Hospital
• Investigators: Principal Investigator: Jianming Tan, professor, Fuzhou General Hospital

Publications and helpful links

General Publications

• Wu Z, Xu X, Cai J, Chen J, Huang L, Wu W, Pugliese A, Li S, Ricordi C, Tan J. Prevention of chronic diabetic complications in type 1 diabetes by co-transplantation of umbilical cord mesenchymal stromal cells and autologous bone marrow: a pilot randomized controlled open-label clinical study with 8-year follow-up. Cytotherapy. 2022 Apr;24(4):421-427. doi: 10.1016/j.jcyt.2021.09.015. Epub 2022 Jan 25.
• Cai J, Wu Z, Xu X, Liao L, Chen J, Huang L, Wu W, Luo F, Wu C, Pugliese A, Pileggi A, Ricordi C, Tan J. Umbilical Cord Mesenchymal Stromal Cell With Autologous Bone Marrow Cell Transplantation in Established Type 1 Diabetes: A Pilot Randomized Controlled Open-Label Clinical Study to Assess Safety and Impact on Insulin Secretion. Diabetes Care. 2016 Jan;39(1):149-57. doi: 10.2337/dc15-0171. Epub 2015 Dec 1.

Study record dates

Study Major Dates

• Study Start: January 1, 2009
• Primary Completion (Actual): December 1, 2010
• Study Completion (Anticipated): December 1, 2014

Study Registration Dates

• First Submitted: June 15, 2011
• First Submitted That Met QC Criteria: June 15, 2011
• First Posted (Estimate): June 16, 2011

Study Record Updates

• Last Update Posted (Estimate): November 20, 2012
• Last Update Submitted That Met QC Criteria: November 18, 2012
• Last Verified: November 1, 2012

More Information

Terms related to this study

• Keywords: type 1 diabetes mellitus; mononuclear cell; umbilical mesenchymal stem cell
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1
• Other Study ID Numbers: UCMSC-T1DM