MSC and MC in Type 2 Diabetes Mellitus

Autologous Bone Marrow Mesenchymal Stem Cell and Bone Marrow Mononuclear Cell Infusion in Type 2 Diabetes Mellitus

Cell injury in human islets induced by non-immune mediated inflammation occur in vitro upon hyperglycemia in type 2 diabetes mellitus. Infusion of autologous bone marrow mononuclear cells (MCs) is an emerging therapeutic approach for DM, which showed promising outcomes with mild side effects. Infusion of MCs and autologous bone marrow mesenchymal stem cells in combination might exert enhanced repairing effects. We hypothesized that infusion of these two classes of cells might provide multiple signals for regeneration and improve recovery from inflammation-induced lesion. The effects might be maximized by intra-arterial pancreatic infusion.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2
• Intervention / Treatment: Drug: infusion of MSCs; Drug: infusion MCs; Drug: insulin

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Ability to provide written informed consent.
• Mentally stable and able to comply with the procedures of the study protocol.
• Clinical history compatible with type 2 diabetes (T2DM) as defined by the Expert Committee on the Diagnosis and classification of Diabetes Mellitus
• Onset of T2DM disease at ≥ 35 years of age.
• T2DM duration ≥ 3 and ≤ 20 years at the time of enrollment.
• Basal C-peptide 0.3-2.0 ng/mL
• HbA1c ≥ 7.5 and ≤ 12% before standard medical therapy (SMT). Patients must have been treated with SMT for minimum of 4 months prior to randomization.

Insulin dose and metformin doses should be stable over the 3 months prior to randomization.

• HbA1c ≥ 7.5 and ≤ 9.5% at time of randomization.
• Total insulin daily dose (TDD) at time of randomization should not exceed 1.0 units/day/kg

Exclusion Criteria:

• BMI >35 kg/m2.
• Insulin requirements of > 100 U/day.
• HbA1c >9.5%. (at the time of randomization)
• C-reactive protein (hs-CRP) >3.00
• Uncontrolled blood Pressure: SBP >160 mmHg or DBP >100 mmHg at the time of randomization.
• 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 Hgb 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
• Subjects that are being treated with any medication that could interfere with the outcome of the study such as: Sulfonylureas, Thiazolidinediones and glucagon like peptide 1 (GLP-1) analogues (Exenatide, Byetta), Pramlintide (Amylin), Dipeptidylpeptidase IV (DPP-IV) inhibitors (i.e. Sitagliptin, Januvia)
• Any medical condition that, in the opinion of the investigator, will interfere with thesafe 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

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MSC+MC; infusion of BMMSC+BMMNC and insulin injection	Drug: infusion of MSCs; infusion of MSCs; Drug: infusion MCs; infusion of MCs; Drug: insulin; intensive insulin care
Active Comparator: MC; infusion of BMMNC and insulin injection	Drug: infusion MCs; infusion of MCs; Drug: insulin; intensive insulin care
Active Comparator: Insulin; insulin injection	Drug: insulin; intensive insulin care

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
macrovascular complications	8 years
microvascular complications	8 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DPN	diabetes peripheral neuropathy	8 years
MI	myocardial infarction	8 years
angina	angina	8 years
stroke	stroke	8 years
amputation	amputation	8 years
DN	diabetes nephropathy	8 years
DRP	diabetes retinopathy	8 years
pro-DRP	proliferative diabetes retinopathy	8 years
C-peptide AUC	C-peptide area under the curve	1y
insulin AUC	insulin area under the curve	1y
HbA1c	glycated hemoglobin	1y
FBG	fasting hemoglucose	1y
insuline dose	exogenous insulin requirements	1y
fasting C-p	fasting c-peptide	1y
The incidence and severity of adverse events related to the stem cell infusion procedure		8y

Collaborators and Investigators

• Sponsor: Fuzhou General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2011
• Primary Completion (Actual): January 1, 2013
• Study Completion (Actual): January 1, 2020

Study Registration Dates

• First Submitted: October 6, 2012
• First Submitted That Met QC Criteria: October 30, 2012
• First Posted (Estimate): November 1, 2012

Study Record Updates

• Last Update Posted (Actual): January 12, 2023
• Last Update Submitted That Met QC Criteria: January 10, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: type 2 diabetes mellitus; mesenchymal stem cells; bone marrow mononeclear cells
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin
• Other Study ID Numbers: MSC-MC-DM

Drug and device information, study documents

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