Clinical trial NCT02138331: Effect of Microvesicles and Exosomes Therapy on β-cell Mass in Type I Diabetes Mellitus (T1DM)
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
PHASE3
Conditions: Diabetes Mellitus Type 1
Keywords: Diabetes Mellitus Type 1
Microvesicles
Exosomes
Cord Blood
Mesenchymal Stem Cells
Lead sponsor: General Committee of Teaching Hospitals and Institutes, Egypt
Sponsor class: OTHER_GOV
First posted: 2014-05-14
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).

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.

Primary outcomes:
measure: Total daily insulin dose
timeFrame: Three months
Secondary outcomes:
measure: Pancreatic β-cell Mass
timeFrame: 3 months
Other outcomes:
measure: Hemoglobin A1c
timeFrame: Three months
Locations:
city: Sahel
country: Egypt
facility: Sahel Teaching Hospital
state: Cairo
city: Shubra
country: Egypt
facility: Sahel Teaching Hospital - General Committee of Teaching Hospitals and Institutes
state: Cairo
city: Shubra
country: Egypt
facility: Sahel Teaching Hospital, General Commettee of Teaching Hospitals and Institutes.
state: Cairo
Study officials:
affiliation: Sahel Teaching Hospital, General Committee of teaching Hospitals and Institutes
name: Wael F Nassar, MD
role: STUDY_CHAIR
affiliation: Cairo University
name: Mervat El Ansary, MD
role: STUDY_DIRECTOR
affiliation: Sahel Teaching Hospital, General Committee of teaching Hospitals and Institutes
name: Abdelnaser A Saad, MSc
role: PRINCIPAL_INVESTIGATOR
affiliation: Sahel Teaching Hospital, General Committee of teaching Hospitals and Institutes
name: Mosaad A Hamid, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Sahel Teaching Hospital, General Committee of teaching Hospitals and Institutes
name: Wael M Esa, MSc
role: PRINCIPAL_INVESTIGATOR
affiliation: Sahel Teaching Hospital, General Committee of teaching Hospitals and Institutes
name: Sameh Shawki, MSc
role: PRINCIPAL_INVESTIGATOR
affiliation: Sahel Teaching Hospital, General Committee of teaching Hospitals and Institutes
name: Marwa Mohammad, MSc
role: PRINCIPAL_INVESTIGATOR
affiliation: Sahel Teaching Hospital, General Committee of teaching Hospitals and Institutes
name: Tamer Shehab, MRCP
role: PRINCIPAL_INVESTIGATOR
affiliation: Cairo University
name: Heba A Ghaffar, MSc
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.