MSC and BMMNC in Type 2 Diabetes Mellitus

• ClinicalTrials.gov Identifier: NCT01719640
• Recruitment Status: Completed
• First Posted: November 1, 2012
• Last Update Posted: April 25, 2018
• Sponsor: Fuzhou General Hospital
• Information provided by (Responsible Party): Jianming Tan, Fuzhou General Hospital

Study Description

Brief Summary:

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 (BMMNCs) is an emerging therapeutic approach for DM, which showed promising outcomes with mild side effects. Infusion of BMMNCs 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.

Condition or disease	Intervention/treatment	Phase
Diabetes Mellitus, Type 2	Drug: infusion of BMMSCs; Drug: infusion BMMNCs; Drug: insulin	Phase 1; Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 22 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Autologous Bone Marrow Mesenchymal Stem Cell and Bone Marrow Mononuclear Cell Infusion in Type 2 Diabetes Mellitus
• Actual Study Start Date: January 2011
• Actual Primary Completion Date: January 2014
• Actual Study Completion Date: January 2015

Arms and Interventions

Arm	Intervention/treatment
Experimental: BMMSC+BMMNC; infusion of BMMSC+BMMNC and insulin injection	Drug: infusion of BMMSCs; infusion of BMMSCs; Drug: infusion BMMNCs; infusion of BMMNCs; Drug: insulin; intensive insulin care
Active Comparator: BMMNC; infusion of BMMNC and insulin injection	Drug: infusion BMMNCs; infusion of BMMNCs; Drug: insulin; intensive insulin care
Active Comparator: Insulin; insulin injection	Drug: insulin; intensive insulin care

Outcome Measures

Primary Outcome Measures :

1. HbA1c [ Time Frame: 1y ]

Secondary Outcome Measures :

1. exogenous insulin requirements [ Time Frame: 1y ]
2. fasting hemoglucose [ Time Frame: 1y ]
3. fasting c-peptide [ Time Frame: 1y ]
4. The incidence and severity of adverse events related to the stem cell infusion procedure [ Time Frame: 1y ]

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

China, Fujian

Fuzhou General Hospital, Xiamen Univ

Fuzhou, Fujian, China, 350025

Sponsors and Collaborators

Fuzhou General Hospital

More Information

• Responsible Party: Jianming Tan, Professor, Fuzhou General Hospital
• ClinicalTrials.gov Identifier: NCT01719640
• Other Study ID Numbers: MSC-BMMNC-DM
• First Posted: November 1, 2012
• Last Update Posted: April 25, 2018
• Last Verified: April 2018

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Jianming Tan, Fuzhou General Hospital:

mesenchymal stem cells; bone marrow mononeclear cells; type 2 diabetes mellitus

Additional relevant MeSH terms:

Diabetes Mellitus; Diabetes Mellitus, Type 2; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Insulin; Hypoglycemic Agents; Physiological Effects of Drugs