Bone Marrow Mononuclear Cell and Hyperbaric Oxygen Therapy in Diabetes Mellitus

NCT00767260 | Completed Phase 1 DMC

• 1 other identifier: sc-dm-2008
• Study Type: interventional
• Target: 82
• Locations: 1 country
• Sites: 1

Brief Summary

There were evidences that the non-immune mediated inflammatory pathways of cell damage occurred in vitro in human islets upon hyperglycemia in type 2 diabetes mellitus. Autologous stem cell therapies were an emerging set of therapies that showed promise with a low side effect profile. we hypothesized that infusion of mononuclear cells from buffy coat obtained from bone marrow might provide multiple signals for regeneration and inflammation-induced lesion recovery of local tissues, of which the effect might be maximized by intra-arterial pancreatic infusion through angiography and combination with hyperbaric oxygen therapy. This trail includes a foregoing sub-trial that investigate the feasibility and safety of a novel method for massive bone marrow collection. The traditional BM collecting procedure is unfavorable because it yields minor bone marrow. Studies have shown that physiological exercise can increase bone marrow blood flow, which might facilitate BM collection. We plan to include a total of 60 patients with type 2 diabetes and randomly assign them to either a control group or an exercise group (n =30 each). The patients in the exercise group exercised 30 minutes before the operation. All patients underwent routine surgical care. The collected BM volume, operation time, collecting speed , puncture times and pain scores during the operation were recorded. Bone marrow samples were tested for CD34+ flow cytometry and whole blood cell count.

Conditions

Type 2 Diabetes Mellitus

Keywords

type 2 diabetes mellitus; bone marrow mononuclear cell; hyperbaric oxygen therapy

Outcome Measures

Primary Outcomes (1)

• area under the curve of c-peptide

  1 year

Secondary Outcomes (7)

• The incidence and severity of adverse events related to the stem cell infusion procedure

  1 year

• The incidence and severity of adverse events related to the hyperbaric oxygen therapy

  1 year

• HbA1c

  1 year

• exogenous insulin requirements

  1 year

• fasting hemoglucose

  1 year

Study Arms (4)

BM-MNC+HOT

EXPERIMENTAL

Autologous Bone Marrow Mononuclear cell Infusion Combined With Hyperbaric Oxygen Therapy

Drug: BM-MNC+HOT

BM-MNC

EXPERIMENTAL

Autologous Bone Marrow mononuclear cell Infusion

Drug: BM-MNC

HOT

EXPERIMENTAL

hyperbaric oxygen therapy

Device: HOT

Control

ACTIVE COMPARATOR

stand medical therapy (enhanced hemoglucose monitor, health and diet counseling and insulin injection)

Drug: SMT

Interventions

BM-MNC+HOT DRUG

Autologous Bone Marrow Mononuclear cell Infusion Combined With Hyperbaric Oxygen Therapy

BM-MNC+HOT

BM-MNC DRUG

Autologous Bone Marrow Mononuclear cell Infusion

BM-MNC

HOT DEVICE

Hyperbaric Oxygen Therapy

HOT

SMT DRUG

hypoglycemic drugs or exogenous insulin

Also known as: stand medical therapy (enhanced hemoglucose monitor, health and diet counseling and insulin injection)

Control

Eligibility Criteria

• Age: 40 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 0.3-2.0 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Fuzhou General Hospital: lead

Study Sites (1)

Fuzhou General Hospital

Fuzhou, Fujian, 350025, China

Location

Related Publications (2)

• Wu Z, Luo F, Wu Z, Tao X, Zou X, Tan J. Preoperative exercise facilitates abundant bone marrow collection in patients with type 2 diabetes for mononuclear cell therapy. Cytotherapy. 2015 Apr;17(4):454-7. doi: 10.1016/j.jcyt.2014.11.007. Epub 2015 Jan 2.

  PMID: 25559146 DERIVED

• Wu Z, Cai J, Chen J, Huang L, Wu W, Luo F, Wu C, Liao L, Tan J. Autologous bone marrow mononuclear cell infusion and hyperbaric oxygen therapy in type 2 diabetes mellitus: an open-label, randomized controlled clinical trial. Cytotherapy. 2014 Feb;16(2):258-65. doi: 10.1016/j.jcyt.2013.10.004. Epub 2013 Nov 28.

  PMID: 24290656 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Health; Insulin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Population Characteristics; Proinsulin; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Jianming Tan, professor

  professor

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Vice President

Study Record Dates

• First Submitted: October 6, 2008
• First Posted: October 7, 2008
• Study Start: March 1, 2008
• Primary Completion: March 1, 2012
• Study Completion: March 1, 2015
• Last Updated: September 21, 2017

Record last verified: 2017-09

Locations

CN (1)