Ignite Creation Date:
2024-05-06 @ 9:13 AM
Last Modification Date:
2024-10-26 @ 12:11 PM
Study NCT ID:
NCT02926963
Status:
TERMINATED
Last Update Posted:
2017-09-29
First Post:
2016-10-04
Brief Title:
Generation of Powerful Biological Tools for Understanding the Pathophysiology of Chronic Granulomatous Disease
Sponsor:
University Hospital Grenoble
Organization:
University Hospital Grenoble
Study Overview
Official Title:
Generation of Powerful Biological Tools - Fibroblast or Inducible Pluripotent Bone Marrow Cells - for Understanding the Pathophysiology of Chronic Granulomatous Disease
Status:
TERMINATED
Status Verified Date:
2017-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
insufficient recruitment
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
FIBRO CGD
Brief Summary:
Chronic granulomatous disease CGD is a rare genetic disease of innate immune due to the malfunction of phagocytic cells unable to destroy pathogens during infection The four genes implicated are CYBB CYBA NCFA and NCF2 respectively encoding Nox2 p22phox p47phox and p67phox Nox2 analogs have recently been discovered in cells other than phagocytes So the question arises on physiopathological impact of the absence of theses proteins not only in phagocytes but also in other cells types such as fibroblasts or neurons
The principal objective is thus to study the impact of protein deficits Nox2 and p22phox in the pathophysiology of neurons from inducible pluripotent bone marrow cells iPSC
For this purpose a collection was built of fibroblasts and keratinocytes from patients with different forms of CGD to get iPSC similar to embryonic marrow cells and differentiable into several cell types neurons phagocytes
The principal objective is thus to study the impact of protein deficits Nox2 and p22phox in the pathophysiology of neurons from inducible pluripotent bone marrow cells iPSC
For this purpose a collection was built of fibroblasts and keratinocytes from patients with different forms of CGD to get iPSC similar to embryonic marrow cells and differentiable into several cell types neurons phagocytes
Detailed Description:
Non randomised pilot descriptive multicentric study Since recently it has been shown that Nox2p22phox protein is expressed not only in phagocytic cells but also in non-phagocytic cells such as fibroblasts epithelial cells vascular cells neurons If pathological consequences of the deficiency Nox2 and p22phox essential to the production of bactericidal toxic derivatives at the level of phagocytic cells is well documented impact of their absence in other types of non-phagocytic cells is not known A better understanding of the impact of the absence of these proteins in these tissues could improve the management of CGD patients by providing a more specific monitoring of their condition Similarly the formation of different cell models of all genetic forms of CGD that do not exist at present will be of great use to study the physiopathology of this disease and as tools for future studies
The study requires the inclusion of minor subjects as CGD is usually diagnosed in early childhood 2 years it is rare frequency 1200 000 and the life expectancy is reduced
To elaborate the cells collection hair and skin biopsy are necessary They will be performed under local anesthesia for adults and during a planned general anesthesia for minors
Fibroblasts and keratinocytes in culture will be obtained by conventional control methods and the absence of expression of p22phox or Nox2 will be checked
Measurement of the kinetics of neuronal development and apoptosis iPSC will be performed in a differentiation system 2 dimensions on stromal cells MS5 For that markers of neuronal differentiation of each step will be measured
Measurement of Reactive Oxygen Species ROS in phagocytes and p22phox deficient Nox2 from differentiation from iPSC chemiluminescence flow cytometry will be performed
Measurement of the effectiveness of phagocytosis phagocytic function in phagocytes deficient p22phox and Nox2 from differentiation from iPSC flow cytometry will be performed
The absence of protein and p22phox Nox2 in phagocytes and p22phox deficient Nox2 from differentiation from the iPSC western blot flow cytometry will be verified
Kinetic of transformation of fibroblasts derived from CGD patients with deficiency or p22phox Nox2 in myofibroblasts will be measured
To answer the principal objective of this study the recruitment of 10 patients will be necessary
The study requires the inclusion of minor subjects as CGD is usually diagnosed in early childhood 2 years it is rare frequency 1200 000 and the life expectancy is reduced
To elaborate the cells collection hair and skin biopsy are necessary They will be performed under local anesthesia for adults and during a planned general anesthesia for minors
Fibroblasts and keratinocytes in culture will be obtained by conventional control methods and the absence of expression of p22phox or Nox2 will be checked
Measurement of the kinetics of neuronal development and apoptosis iPSC will be performed in a differentiation system 2 dimensions on stromal cells MS5 For that markers of neuronal differentiation of each step will be measured
Measurement of Reactive Oxygen Species ROS in phagocytes and p22phox deficient Nox2 from differentiation from iPSC chemiluminescence flow cytometry will be performed
Measurement of the effectiveness of phagocytosis phagocytic function in phagocytes deficient p22phox and Nox2 from differentiation from iPSC flow cytometry will be performed
The absence of protein and p22phox Nox2 in phagocytes and p22phox deficient Nox2 from differentiation from the iPSC western blot flow cytometry will be verified
Kinetic of transformation of fibroblasts derived from CGD patients with deficiency or p22phox Nox2 in myofibroblasts will be measured
To answer the principal objective of this study the recruitment of 10 patients will be necessary
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 2009-A00944-53 | OTHER | ID RCB | None |