Phase 1 Study of The Effect of Cell-Free Cord Blood Derived Microvesicles On β-cell Mass in Type 1 Diabetes Mellitus (T1DM) Patients

Effect of Microvesicles and Exosomes Therapy on β-cell Mass in Type I Diabetes Mellitus (T1DM)

Sponsors

Lead sponsor: General Committee of Teaching Hospitals and Institutes, Egypt

Source General Committee of Teaching Hospitals and Institutes, Egypt
Brief Summary

Type 1 diabetes mellitus is strictly autoimmune mediated disease destructing the islets β-cell of the pancreas. Mesenchymal stem cells and its microvesicles are reported as an anti-inflammatory agents. We hypothesis that intravenous infusion of cell free umbilical cord-blood derived MSC microvesicles may reduce the inflammatory state and hence improve the β-cell mass as well as the glycemic control of the patients of T1DM.

Detailed Description

- Twenty T1DM patients, age between 18-60 years with reduction of C-peptide chain more than 50%, C-peptide of more than 0.8 ng/mL at Screening and requiring insulin ≥0.4 IU per kg per day.

- Twenty T1DM patients of the same entry selection criteria will be subjected to all steps except the microvesicles administration as a control group.

- Study follow up period: Three months

- Gender: Both males and females are included

- Entry selection criteria include:

UACR less than 300, BUN between 10-20 mg/dl, serum creatinin between 0.6-1.4 mg/dl and normal liver enzymes, normal serum bilirubin, normal serum albumin and coagulation profile). C-peptide of more than 0.8 ng/mL at Screening. BMI 20-40 kgm/m2 - Exclusion criteria: Other autoimmune diseases. Pregnancy. Previous treatment with stem cells. All patients and controls will be investigated for HBV, HCV & HIV by PCR test before enrollment in the study and positivity for any of these parameters means exclusion of this patient from the study.

- The primary end point will be the end of three months follow up. At day (0):All patients and controls will be subjected to the following investigations: Liver functions tests, kidney functions tests, HbA1c, glucose tolerance test (GTT), fasting and 2 hrs.post prandial blood glucose levels, C-peptide chain level and calculated total daily insulin dose.

After three months (at the end of the study) the same investigations will be repeated.

Two intravenous infusions of cell free cord-blood derived mesenchymal stem cells [CB-MSC] microvesicles:

- The first dose will be purified exosomes, ranging between 40-180 nm, in a dose of the supernatant produced from (1.22-1.51) × 10 (6)/kg/IV.

(Characterization of exosomes:CD63, CD9, Alix, TSG 101, HSP 70).

- The second dose, after 7 days, will be the microvesicles, ranging between 180-1000 nm, in a dose of the supernatant produced from (1.22-1.51) × 10 (6)/kg/IV.

(Characterization of microvesicles: (Annexin V, Flotillin-2, selectin,integrin, CD40 metalloproteinase).

Overall Status Unknown status
Start Date April 2014
Completion Date September 2014
Primary Completion Date July 2014
Phase Phase 2/Phase 3
Study Type Interventional
Primary Outcome
Measure Time Frame
Total daily insulin dose Three months
Secondary Outcome
Measure Time Frame
Pancreatic β-cell Mass 3 months
Enrollment 20
Condition
Intervention

Intervention type: Biological

Intervention name: MSC exosomes.

Description: Exosomes: (Size) 40-100 nm, (markers) CD63, CD9, Alix, TSG 101, HSP 70 Microvesicles: (Size) 100-1000 nm, (markers) Annexin V, Flotillin-2, selectin, integrin, CD40 metalloproteinase

Arm group label: Exosomes

Eligibility

Criteria:

Inclusion Criteria:

- UACR less than 300, BUN between 10-20 mg/dl, serum creatinin between 0.6-1.4 mg/dl and normal liver enzymes, normal serum bilirubin, normal serum albumin and coagulation profile). C-peptide more than 0.8 ng/mL at Screening. BMI 20-40 kgm/m2.

Exclusion Criteria:

- Other autoimmune diseases. Pregnancy. Previous treatment with stem cells. All patients and controls will be investigated for HBV, HCV & HIV by PCR test before enrollment in the study and positivity for any of these parameters means exclusion of this patient from the study.

Gender: All

Minimum age: 18 Years

Maximum age: 60 Years

Healthy volunteers: No

Overall Official
Location
facility
Sahel Teaching Hospital | Sahel, Cairo, 11522, Egypt
Sahel Teaching Hospital - General Committee of Teaching Hospitals and Institutes | Shubra, Cairo, 11522, Egypt
Sahel Teaching Hospital, General Commettee of Teaching Hospitals and Institutes. | Shubra, Cairo, 11522, Egypt
Location Countries

Egypt

Verification Date

May 2014

Responsible Party

Responsible party type: Principal Investigator

Investigator affiliation: General Committee of Teaching Hospitals and Institutes, Egypt

Investigator full name: Wael Fouad Nassar

Investigator title: Senior Consultant of Nephrology.

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 1
Arm Group

Arm group label: Exosomes

Arm group type: Experimental

Description: The exosomes have exosome-associated proteins such as the tetraspanin proteins, CD9 and CD81, Alix, Tsg101, and RNA that consists primarily of short RNAs of less than 300 nm. Some of these RNAs are microRNAs that are predominantly pre-microRNAs..Additionally, CB-SC displayed very low immunogenicity as indicated by expression of a very low level of major histocompatibility complex (MHC) antigens and failure to stimulate the proliferation of allogeneic lymphocytes.

Study Design Info

Allocation: N/A

Intervention model: Single Group Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Source: ClinicalTrials.gov