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

NCT ID: NCT01374854

Last Updated: 2012-11-20

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 44 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-01-31
• Study Completion Date: 2014-12-31

Brief Summary

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.

Conditions

Type 1 Diabetes Mellitus

Keywords

type 1 diabetes mellitus; umbilical mesenchymal stem cell; mononuclear cell

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Stem Cell Infusion

Group Type: EXPERIMENTAL

Umbilical mesenchymal stem cell (UC-MSCs) infusion

Intervention Type: BIOLOGICAL

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.

traditional therapy control

Group Type: ACTIVE_COMPARATOR

traditional therapy

Intervention Type: DRUG

exogenous insulin injection daily

Interventions

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.

Intervention Type: BIOLOGICAL

traditional therapy

exogenous insulin injection daily

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fuzhou General Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jianming Tan, professor

Role: PRINCIPAL_INVESTIGATOR

Fuzhou General Hospital

Locations

Fuzhou General Hospital

Fuzhou, Fujian, China

Countries

China

References

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.

Reference Type: DERIVED

PMID: 35086778 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 26628416 (View on PubMed)

Other Identifiers

UCMSC-T1DM

Identifier Type: -

Identifier Source: org_study_id