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

NCT ID: NCT02138331

Last Updated: 2014-05-14

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-04-30
• Study Completion Date: 2014-09-30

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).

Conditions

Diabetes Mellitus Type 1

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Exosomes

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.

Group Type: EXPERIMENTAL

MSC exosomes.

Intervention Type: BIOLOGICAL

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

Interventions

MSC exosomes.

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

Intervention Type: BIOLOGICAL

Other Intervention Names

Extacellular vesicles; Microvesicles

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

General Committee of Teaching Hospitals and Institutes, Egypt

OTHER_GOV

Sponsor Role: lead

Responsible Party

Wael Fouad Nassar

Senior Consultant of Nephrology.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Wael F Nassar, MD

Role: STUDY_CHAIR

Sahel Teaching Hospital, General Committee of teaching Hospitals and Institutes

Mervat El Ansary, MD

Role: STUDY_DIRECTOR

Cairo University

Abdelnaser A Saad, MSc

Role: PRINCIPAL_INVESTIGATOR

Sahel Teaching Hospital, General Committee of teaching Hospitals and Institutes

Mosaad A Hamid, MD

Role: PRINCIPAL_INVESTIGATOR

Sahel Teaching Hospital, General Committee of teaching Hospitals and Institutes

Wael M Esa, MSc

Role: PRINCIPAL_INVESTIGATOR

Sahel Teaching Hospital, General Committee of teaching Hospitals and Institutes

Sameh Shawki, MSc

Role: PRINCIPAL_INVESTIGATOR

Sahel Teaching Hospital, General Committee of teaching Hospitals and Institutes

Marwa Mohammad, MSc

Role: PRINCIPAL_INVESTIGATOR

Sahel Teaching Hospital, General Committee of teaching Hospitals and Institutes

Tamer Shehab, MRCP

Role: PRINCIPAL_INVESTIGATOR

Sahel Teaching Hospital, General Committee of teaching Hospitals and Institutes

Heba A Ghaffar, MSc

Role: PRINCIPAL_INVESTIGATOR

Cairo University

Locations

Sahel Teaching Hospital

Sahel, Cairo Governorate, Egypt

Sahel Teaching Hospital - General Committee of Teaching Hospitals and Institutes

Shubrā, Cairo Governorate, Egypt

Sahel Teaching Hospital, General Commettee of Teaching Hospitals and Institutes.

Shubrā, Cairo Governorate, Egypt

Countries

Egypt

References

Ezquer F, Ezquer M, Contador D, Ricca M, Simon V, Conget P. The antidiabetic effect of mesenchymal stem cells is unrelated to their transdifferentiation potential but to their capability to restore Th1/Th2 balance and to modify the pancreatic microenvironment. Stem Cells. 2012 Aug;30(8):1664-74. doi: 10.1002/stem.1132.

Reference Type: RESULT

PMID: 22644660 (View on PubMed)

Related Links

http://www.biomedcentral.com/1741-7015/10/3/prepub

doi:10.1186/1741-7015-10-3 Cite this article as: Zhao et al.: Reversal of type 1 diabetes via islet b cell regeneration following immune modulation by cord blood-derived multipotent stem cells. BMC Medicine 2012 10:3.

Other Identifiers

Cell Free MSC Exo

Identifier Type: -

Identifier Source: secondary_id

666666

Identifier Type: -

Identifier Source: org_study_id