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

Diabetes Mellitus Type 1 Clinical Trial

Official title:

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

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT02138331
• Other study ID #: 666666
• Secondary ID: Cell Free MSC Ex
• Status: Enrolling by invitation
• Phase: Phase 2/Phase 3
• First received: May 12, 2014
• Last updated: May 12, 2014
• Start date: April 2014
• Est. completion date: September 2014

Study information

• Verified date: May 2014
• Source: General Committee of Teaching Hospitals and Institutes, Egypt
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 20
• Est. completion date: September 2014
• Est. primary completion date: July 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 60 Years

Eligibility

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.

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus Type 1
• Diabetes Mellitus, Type 1

Intervention

Biological:
• 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

Locations

Country	Name	City	State
Egypt	Sahel Teaching Hospital	Sahel	Cairo
Egypt	Sahel Teaching Hospital - General Committee of Teaching Hospitals and Institutes	Shubra	Cairo
Egypt	Sahel Teaching Hospital, General Commettee of Teaching Hospitals and Institutes.	Shubra	Cairo

Sponsors (1)

Lead Sponsor	Collaborator
General Committee of Teaching Hospitals and Institutes, Egypt

Country where clinical trial is conducted

Egypt, 

References & Publications (1)

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 microenviron — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Hemoglobin A1c	HbA1c levels before enrollment and at the end of the study	Three months	Yes
Primary	Total daily insulin dose	All T1DM patients with identified pre-study insulin dose and exosomes and microvesicles will be given then weekly follow up of the total daily insulin dose will be measured. After 3 months We calculate the total daily dose of insulin that maintain the RBS levels between 120-160 mg/dl at any point of the evaluation period.	Three months	Yes
Secondary	Pancreatic ß-cell Mass	Pancreatic ß-cell Mass levels will be assessed before and after the 3 months study period of time.	3 months	No

External Links

•   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.