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Bone Marrow Progenitor Cell Mobilization in Diabetes (GCSF-DM)

This study is currently recruiting participants.
Verified April 2012 by University of Padova
Sponsor:
Information provided by (Responsible Party):
Angelo Avogaro, University of Padova
ClinicalTrials.gov Identifier:
NCT01102699
First received: April 9, 2010
Last updated: April 20, 2012
Last verified: April 2012
History of Changes
  Purpose

Diabetes mellitus is associated with a significant reduction of circulating progenitor cells (CPCs). These include endothelial progenitor cells (EPCs), which are involved in cardiovascular homeostasis and repair. A reduction of CPCs in metabolic patients is associated with an increased risk of future adverse cardiovascular outcomes. Therefore, ways to active stimulate an increase of CPC levels in diabetes are actively pursued.

Experimental animal studies and preliminary data in humans indicate that a bone marrow defect is causally related to the low CPC level in diabetes.

Our previous data in rats indicate that diabetes reduces the bone marrow responsiveness to granulocyte colony-stimulating factor (G-CSF) in terms of progenitor cell mobilization.

In the present study, we aim at investigating bone marrow responsiveness to pharmacological mobilization of CPC in diabetic patients as compared to non-diabetic subjects.


Condition Intervention Phase
Diabetes Mellitus
 Drug: Filgrastim, hrG-CSF
 Phase 4

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: Bone Marrow Responsiveness to Pharmacologic Mobilization of Progenitor Cells in Diabetic Versus Non-diabetic Patients

Resource links provided by NLM:

MedlinePlus related topics: Diabetes
U.S. FDA Resources

Further study details as provided by University of Padova:

Primary Outcome Measures:
  • CPC mobilization after a single G-CSF dose [ Time Frame: 0-24 hours ] [ Designated as safety issue: No ]

    Circulating progenitor cell level will be assessed before and 24 hours after a single G-CSF dose in both diabetic and non diabetic patients.

    Change in CPC level will be indicative of bone marrow mobilization. Mobilization will be compared in diabetic versus non diabetic subjects.



Estimated Enrollment: 48
Study Start Date: June 2010
Estimated Study Completion Date: September 2013
Estimated Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Filgrastim, G-CSF
Single s.c. dose of G-CSF (300 microg)
 Drug: Filgrastim, hrG-CSF
Single subcutaneous injection of Filgrastim (hrG-CSF) 300 microg (30 MU)

Detailed Description:

Diabetes mellitus is associated with a significant reduction of circulating progenitor cells (CPCs). CPCs are defined by the surface expression of the stem cell antigen CD34 and or CD133. These cells include endothelial progenitor cells (EPCs), which are involved in cardiovascular homeostasis and repair. EPCs are characterized by the co-expression of endothelial antigen(s), such as KDR.

A reduction of CPCs in metabolic patients is associated with an increased risk of future adverse cardiovascular outcomes, such as myocardial infarction, stroke, revascularization, etc. Therefore, ways to active stimulate an increase of CPC levels in diabetes are actively pursued. Indeed, there are several drugs that stimulate CPCs or EPCs, but it is not fully clear if they are active also in diabetic patients.

The mechanisms that account for CPC reduction in diabetes include defective bone marrow mobilization, reduced survival and increased homing outside the bloodstream. Experimental animal studies and preliminary data in humans indicate that a bone marrow defect is causally related to the low CPC level in diabetes.

Our previous data in rats indicate that diabetes reduces the bone marrow responsiveness to G-CSF in terms of c-kit+/Sca-1+ progenitor cell mobilization.

There is also some experimental evidence in type 2 diabetic rats that a specific form of autonomic neuropathy impairs bone marrow mobilization of progenitor cells.

In the present study, we aim at investigating bone marrow responsiveness to pharmacological mobilization of CPC in diabetic patients as compared to non-diabetic subjects.

Diabetic subjects and control subjects will be administered with a single dose of granulocyte colony stimulating factor (G-CSF) and progenitor cells will be quantified before and 24 hours after G-CSF administration. Progenitor cells will be analyzed by flow cytometry on the basis of the expression of CD34, CD133 and KDR.

Mean percentage variation of CPCs and EPCs will be compared in diabetic versus non diabetic patients to understand whether or not diabetes is associated with a significant defective mobilization of progenitor cells.

As a secondary aim, diabetic patients will be divided in those with and without diabetic autonomic neuropathy (DAN) to understand if DAN modulates bone marrow responsiveness to G-CSF.

  Eligibility

Ages Eligible for Study:   25 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Diabetes mellitus (for cases) or absence of diabetes (for controls);
  • Age 25-65;
  • Both sexes;
  • Capability of providing informed consent.

Exclusion Criteria:

  • Age <25 or >65;
  • Fertile women;
  • Recent (within 2 months) acute illnesses;
  • Chronic immune of infectious diseases;
  • Current or remote hematological disorders;
  • Leukocytosis, leukopenia or thrombocytopenia;
  • Organ transplantation or immune suppression;
  • Altered liver function;
  • Severe renal failure (eGFR<30 mL/min/m2);
  • Anomalies in lymphocytes subpopulations;
  • High basal level of CD34+ cell count;
  • Allergy to Filgrastim;
  • Bronchial asthma or other chronic lung disorders;
  • Current or remote cancer;
  • Deny or impossibility to provide informed consent.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01102699

Contacts
Contact: Angelo Avogaro, MD PhD 00390498212178 ext 2178 angelo.avogaro@unipd.it
Contact: Gian Paolo Fadini, MD 00390498212172 ext 2172 gianpaolo.fadini@unipd.it

Locations
Italy
University Hospital, Division of Metabolic Diseases Recruiting
Padova, Italy, 35100
Contact: Angelo Avogaro, MD PhD     00390498212178 ext 2178     angelo.avogaro@unipd.it    
Contact: Gian Paolo Fadini, MD     00390498214318 ext 4318     gianpaolo.fadini@unipd.it    
Principal Investigator: Angelo Avogaro, MD PhD            
Sponsors and Collaborators
University of Padova
Investigators
Principal Investigator: Angelo Avogaro, MD PhD Dept. of Medicine, University of Padova, Medical School, Padova (Italy)
Study Director: Gian Paolo Fadini, MD Department of Medicine, University of Padova.
  More Information

No publications provided by University of Padova

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Angelo Avogaro, Professor of Endocrinology, University of Padova
ClinicalTrials.gov Identifier: NCT01102699     History of Changes
Other Study ID Numbers: GCSF-DM
Study First Received: April 9, 2010
Last Updated: April 20, 2012
Health Authority: Italy: National Monitoring Centre for Clinical Trials - Ministry of Health
Italy: Ethics Committee

Keywords provided by University of Padova:
Diabetes
stem cells
bone marrow
mobilization

Additional relevant MeSH terms:
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Lenograstim
 Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 16, 2013