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Autologous Mesenchymal Stem Cell and Bone Marrow Stem Cell Infusion Combined With Hyperbaric Oxygen Therapy in Type 2 Diabetes Mellitus
This study is currently recruiting participants.
Verified by Fuzhou General Hospital, October 2008
Sponsored by: Fuzhou General Hospital
Information provided by: Fuzhou General Hospital
ClinicalTrials.gov Identifier: NCT00767260
  Purpose

There is evidence that the non-immune mediated inflammatory pathways of cell damage occur in vitro in human islets upon hyperglycemia. Autologous stem cell therapies are an emerging set of therapies that show promise with a low side effect profile. we hypothesize that infusion of mononuclear cells from buffy coat obtained from bone marrow may provide multiple signals for regeneration and inflammation-induced lesion recovery of local tissues, of which the effect may be maximized by intra-arterial pancreatic infusion through angiography and combination with hyperbaric oxygen therapy, and simultaneous infusion of large amount of cultured mesenchymal stem cells may promote local regeneration and differentiation, as well as decrease the risk of cell infusion related pancreatitis.


Condition Intervention Phase
Type 2 Diabetes Mellitus
Biological: MSC, BMSC, HOT
Biological: BMSC, HOT
Biological: BMSC
Biological: HOT
Phase I
Phase II

MedlinePlus related topics: Diabetes
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Randomized, Open Label, Active Control, Factorial Assignment, Safety/Efficacy Study

Further study details as provided by Fuzhou General Hospital:

Primary Outcome Measures:
  • HbA1c [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • The incidence and severity of adverse events related to the stem cell infusion procedure [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
  • The incidence and severity of adverse events related to the hyperbaric oxygen therapy [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
  • proportion of subjects with a reduction of ≥1% in HbA1c [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • The percent reduction in insulin requirements [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • The reduction in/cessation of oral hypoglycemic agents [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • The increase in basal and stimulated C-peptide as measured by oral glucose tolerance test (OGTT) [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • The reduction in FPG [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Estimated Enrollment: 100
Study Start Date: March 2008
Estimated Study Completion Date: March 2010
Estimated Primary Completion Date: March 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
1: Experimental
Autologous Mesenchymal Stem Cell and Bone Marrow Stem Cell Infusion Combined With Hyperbaric Oxygen Therapy
Biological: MSC, BMSC, HOT
Autologous Mesenchymal Stem Cell and Bone Marrow Stem Cell Infusion Combined With Hyperbaric Oxygen Therapy
2: Experimental
Autologous Bone Marrow Stem Cell Infusion Combined With Hyperbaric Oxygen Therapy
Biological: BMSC, HOT
Autologous Bone Marrow Stem Cell Infusion Combined With Hyperbaric Oxygen Therapy
3: Experimental
Autologous Bone Marrow Stem Cell Infusion alone
Biological: BMSC
Autologous Bone Marrow Stem Cell Infusion alone
4: Experimental
Hyperbaric Oxygen Therapy alone
Biological: HOT
Hyperbaric Oxygen Therapy alone

  Eligibility

Ages Eligible for Study:   35 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male and female patients age 40 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 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 0.4-2.2 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 100 units/day

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 with a history of chronic sinusitis (sinusitis lasting more than 8 weeks in the past year) or recurrent acute sinusitis (sinusitis lasting more than 4 weeks more than four times in the past year.
  • Any contraindication to hyperbaric oxygen treatment
  • 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), Dipeptidyl-peptidase IV (DPP-IV) inhibitors (i.e. Sitagliptin, Januvia)
  • Any medical condition that, in the opinion of the investigator, will interfere with the safe completion of the trial.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00767260

Contacts
Contact: Jianming Tan, Professor 008613375918000 doctortjm@yahoo.com

Locations
China, FUJIAN
Fuzhou General Hospital Recruiting
FUZHOU, FUJIAN, China, 350025
Sponsors and Collaborators
Fuzhou General Hospital
Investigators
Principal Investigator: Jianming Tan, professor professor
  More Information

Responsible Party: FUZHOU GENERAL HOSPITAL ( FUZHOU GENERAL HOSPITAL )
Study ID Numbers: sc-dm-2008
Study First Received: October 6, 2008
Last Updated: October 6, 2008
ClinicalTrials.gov Identifier: NCT00767260  
Health Authority: China: State Food and Drug Administration

Keywords provided by Fuzhou General Hospital:
type 2 diabetes mellitus
bone marrow stem cell
mesenchymal stem cell
hyperbaric oxygen therapy

Study placed in the following topic categories:
Metabolic Diseases
Diabetes Mellitus, Type 2
Diabetes Mellitus
Endocrine System Diseases
Endocrinopathy
Metabolic disorder
Glucose Metabolism Disorders

ClinicalTrials.gov processed this record on January 16, 2009