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

May 12, 2014 updated by: Wael Fouad Nassar, General Committee of Teaching Hospitals and Institutes, Egypt

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

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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).

Study Type

Interventional

Enrollment (Anticipated)

20

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Egypt
    • Cairo
      • Sahel, Cairo, Egypt, 11522
        • Sahel Teaching Hospital
      • Shubra, Cairo, Egypt, 11522
        • Sahel Teaching Hospital - General Committee of Teaching Hospitals and Institutes
      • Shubra, Cairo, Egypt, 11522
        • Sahel Teaching Hospital, General Commettee of Teaching Hospitals and Institutes.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 58 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
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
Other Names:
  • Extacellular vesicles
  • Microvesicles

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Total daily insulin dose
Time Frame: Three months
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

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pancreatic β-cell Mass
Time Frame: 3 months
Pancreatic β-cell Mass levels will be assessed before and after the 3 months study period of time.
3 months

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Hemoglobin A1c
Time Frame: Three months
HbA1c levels before enrollment and at the end of the study
Three months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

General Committee of Teaching Hospitals and Institutes, Egypt

Investigators

  • Study Chair: Wael F Nassar, MD, Sahel Teaching Hospital, General Committee of teaching Hospitals and Institutes
  • Study Director: Mervat El Ansary, MD, Cairo university
  • Principal Investigator: Abdelnaser A Saad, MSc, Sahel Teaching Hospital, General Committee of teaching Hospitals and Institutes
  • Principal Investigator: Mosaad A Hamid, MD, Sahel Teaching Hospital, General Committee of teaching Hospitals and Institutes
  • Principal Investigator: Wael M Esa, MSc, Sahel Teaching Hospital, General Committee of teaching Hospitals and Institutes
  • Principal Investigator: Sameh Shawki, MSc, Sahel Teaching Hospital, General Committee of teaching Hospitals and Institutes
  • Principal Investigator: Marwa Mohammad, MSc, Sahel Teaching Hospital, General Committee of teaching Hospitals and Institutes
  • Principal Investigator: Tamer Shehab, MRCP, Sahel Teaching Hospital, General Committee of teaching Hospitals and Institutes
  • Principal Investigator: Heba A Ghaffar, MSc, Cairo university

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2014

Primary Completion (Anticipated)

July 1, 2014

Study Completion (Anticipated)

September 1, 2014

Study Registration Dates

First Submitted

May 12, 2014

First Submitted That Met QC Criteria

May 12, 2014

First Posted (Estimate)

May 14, 2014

Study Record Updates

Last Update Posted (Estimate)

May 14, 2014

Last Update Submitted That Met QC Criteria

May 12, 2014

Last Verified

May 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 666666
  • Cell Free MSC Exo

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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