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

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ClinicalTrials.gov Identifier: NCT01102699
Recruitment Status : Completed
First Posted : April 13, 2010
Last Update Posted : September 2, 2013
Sponsor:
Information provided by (Responsible Party):
Angelo Avogaro, University of Padova

Tracking Information
First Submitted Date  ICMJE April 9, 2010
First Posted Date  ICMJE April 13, 2010
Last Update Posted Date September 2, 2013
Study Start Date  ICMJE June 2010
Actual Primary Completion Date August 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 12, 2010)
CPC mobilization after a single G-CSF dose [ Time Frame: 0-24 hours ]
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT01102699 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Bone Marrow Progenitor Cell Mobilization in Diabetes
Official Title  ICMJE Bone Marrow Responsiveness to Pharmacologic Mobilization of Progenitor Cells in Diabetic Versus Non-diabetic Patients
Brief Summary

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.

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Condition  ICMJE Diabetes Mellitus
Intervention  ICMJE Drug: Filgrastim, hrG-CSF
Single subcutaneous injection of Filgrastim (hrG-CSF) 300 microg (30 MU)
Study Arms  ICMJE Experimental: Filgrastim, G-CSF
Single s.c. dose of G-CSF (300 microg)
Intervention: Drug: Filgrastim, hrG-CSF
Publications * Fadini GP, Albiero M, Vigili de Kreutzenberg S, Boscaro E, Cappellari R, Marescotti M, Poncina N, Agostini C, Avogaro A. Diabetes impairs stem cell and proangiogenic cell mobilization in humans. Diabetes Care. 2013 Apr;36(4):943-9. doi: 10.2337/dc12-1084. Epub 2012 Oct 30.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Estimated Enrollment  ICMJE
 (submitted: April 12, 2010)
48
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE August 2013
Actual Primary Completion Date August 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 25 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Italy
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01102699
Other Study ID Numbers  ICMJE GCSF-DM
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Angelo Avogaro, University of Padova
Study Sponsor  ICMJE University of Padova
Collaborators  ICMJE Not Provided
Investigators  ICMJE
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.
PRS Account University of Padova
Verification Date August 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP