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Report for Clinical Trial NCT02877212

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

Association of FC Gamma RIIIA Polymorphism and Thrombopoietin (THPO) Expression With Response to TPO Agonists in Refractory ITP and the Impact of Therapy on B and T Cells Subsets in the Patients With Mutated Genotypes

Idiopathic thrombocytopenic purpura (ITP) is an autoimmune disease characterized by antibody-mediated platelet destruction. The complex pathogenesis of ITP with multiple challenges to immune system in terms of genetic predisposition, infection, responsiveness to immunosuppressive therapy (IST) and inhibition of platelet production has proven the diversity of constraints in diagnosing and treating ITP. Thrombopoietin receptor agonist (Eltrombopag) is specifically indicated for the treatment of thrombocytopenia in patients with chronic immune (idiopathic) thrombocytopenic purpura (ITP) who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy. This clinical trial aims to investigate the association of Fc gammaRIIIA gene (V158F) genetic predisposition with treatment outcome of Immune Thrombocytopenia (ITP) in refractory ITP patients and especially with Eltrombopag.

NCT02877212 Immune Thrombocytopenic Purpura (ITP)
MeSH: Purpura Purpura, Thrombocytopenic Purpura, Thrombocytopenic, Idiopathic
HPO: Autoimmune thrombocytopenia Petechiae Purpura

1 Interventions

Name: Eltrombopag

Description: Eltrombopag will be given to steroid refractory ITP patients and ITP patients treated with standard Immunosuppressive therapy (IST) will be taken as control.

Type: Drug

Study subjects


Primary Outcomes

Measure: The overall response rate 4-6 months after treatment defined by a platelet count > 30 x 109/L with at least a two-fold increase from the initial (pre-treatment) count

Time: 6 months after inclusion

Description: The inclusion of 75 patients (25 ITP patients treated with Eltrombopag and 50 subjects with ITP treated with other standard IST) would be considered as sufficient to show an association of the FcgammaRIIIA V158F genotypes distribution and THPO expression with the response for the patients treated with Eltrombopag and other IST at different time points; (M0, M3 and M6 )** **M0=pretreatment sample at 0 month; M3=sample after 3 months of treatment; M6= sample after 6 months of treatment.

Measure: Fc Receptor polymorphism and THPO expression in responders and non-responders

Time: 6-12 months after inclusion

Secondary Outcomes

Description: The Thrombopoietin and cytokine expression among the responders and non responders will be taken as secondary outcome to evaluate the influence of Fc gamma RIIIA mutated genotypes to evaluate the correlation between steroid refractory and control groups.

Measure: The Thrombopoietin and cytokine expression among the responders and non responders

Time: 6 months

Purpose: Treatment

Single Group Assignment


There is one SNP

SNPs


1 V158F

This clinical trial aims to investigate the association of Fc gammaRIIIA gene (V158F) genetic predisposition with treatment outcome of Immune Thrombocytopenia (ITP) in refractory ITP patients and especially with Eltrombopag. --- V158F ---

The inclusion of 75 patients (25 ITP patients treated with Eltrombopag and 50 subjects with ITP treated with other standard IST) would be considered as sufficient to show an association of the FcgammaRIIIA V158F genotypes distribution and THPO expression with the response for the patients treated with Eltrombopag and other IST at different time points; (M0, M3 and M6 )** **M0=pretreatment sample at 0 month; M3=sample after 3 months of treatment; M6= sample after 6 months of treatment.. --- V158F ---

3. Fc gamma RIIIA V158F polymorphism will be assessed by means of an allele-specific PCR and/nested PCR following sequence verification 4. In order to validate the genotypes of study participants; direct sequencing of the SNPs will be done through automated capillary sequencing method. --- V158F ---

8. To find the association of the Fc V158F genotypic distribution with THPO and cytokine expression in THPO agonists responders and nonresponders ; statistical analysis will be performed by using statistical program SPSS (Version 23.0) . --- V158F ---



HPO Nodes


HPO:
Autoimmune thrombocytopenia
Genes 44
KRAS FAS CASP10 CD19 CD81 FAS CTLA4 PRKCD ACP5 TNFRSF13B PRKCD GALC TNFRSF13C KDM6A MS4A1 NFKB1 FASLG NFKB2 CASP10 PNP TNFSF12 CR2 ADA KMT2D ICOS FASLG RFXANK SMPD1 TNFSF12 IL7R FOXP3 TPP2 RFX5 ARHGEF1 CIITA FAS RASGRP1 ZAP70 NRAS RFXAP PRKCD STAT1 STAT3 NFKB2
Petechiae
Genes 55
COL5A2 ITGA2B GFI1B GP1BA GP1BA GP1BA FERMT3 TBL1XR1 CD109 GP1BB JAK2 FIP1L1 GP1BB OCLN SAMD9 CLCN7 WIPF1 BCOR GBA COL5A1 RAB27A ETHE1 IRF2BP2 USP18 ITGB3 FCGR2C PEPD NABP1 CALR ITGB3 PML GP9 WAS PRKAR1A NUMA1 TET2 APOE ITGA2B ITGA2 RARA TREX1 WAS ZBTB16 GATA1 GNA14 NPM1 MPL ETV6 HOXA11 STAT3 STAT5B ETHE1 WAS GATA1 COL1A1
Purpura
Genes 132
COL5A2 CFHR1 STIM1 GP1BB CD19 ITGA2B GFI1B GP1BA GP1BA ITGB3 FERMT3 F13A1 MS4A1 TFR2 NFKB2 GP1BB F13A1 JAK2 GP1BB F2 F13B AIP TBXAS1 GGCX OCLN PROS1 ITGA2B CLCN7 WIPF1 SBDS GBA MPL SH2B3 PROS1 PROC ARL6IP6 TBX1 GP1BB IRF2BP2 USP18 CD81 TERT PEPD ITGB3 PML PRF1 NLRP3 GP9 WAS PRKAR1A TET2 APOE ITGA2B ITGA2 RARA TREX1 WAS TERC ICOS CTLA4 GATA1 TNFSF12 GNA14 NPM1 PROC CFHR3 JAK2 MPL TBXA2R HOXA11 F13B WAS COL1A1 HLA-DPA1 PTPN22 HIRA MYD88 GP1BA MVK PRKCD GP1BA ACP5 PROS1 TNFRSF13B GP9 C2 ORAI1 C4A TBL1XR1 CD109 ADA2 USP8 FIP1L1 CALR SAMD9 RREB1 BCOR HLA-DPB1 GP6 COL5A1 P2RY12 RAB27A ETHE1 ITGA2B ITGB3 CD81 FCGR2C ARVCF NABP1 CALR TNFRSF13C ITGB3 SEC24C CFH NFKB1 NLRC4 NUMA1 TNFSF12 IFNG CR2 ZBTB16 CHST14 JMJD1C PRTN3 TBX1 COMT UFD1 ETV6 STAT3 STAT5B ETHE1 GATA1