SNPMiner Trials by Shray Alag


SNPMiner Trials: Clinical Trial Report


Report for Clinical Trial NCT02877212

Developed by Shray Alag, 2019.
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 33
TNFRSF13C KRAS TPP2 TNFRSF13B CASP10 PRKCD RASGRP1 CD81 CTLA4 GALC KMT2D ICOS NRAS CD19 FAS MS4A1 ADA FASLG CR2 CIITA TNFSF12 RFX5 RFXAP KDM6A ZAP70 RFXANK STAT1 ACP5 NFKB1 STAT3 NFKB2 PNP FOXP3
Petechiae
Genes 42
MPL PEPD GBA JAK2 NPM1 PRKAR1A TET2 HOXA11 GFI1B ETV6 COL5A1 FIP1L1 COL5A2 USP18 TREX1 FCGR2C ZBTB16 ITGA2 SAMD9 ITGA2B RARA NABP1 APOE GNA14 WAS OCLN WIPF1 TBL1XR1 ITGB3 CALR RAB27A ETHE1 STAT5B FERMT3 GP1BA PML GP1BB COL1A1 CD109 NUMA1 GATA1 GP9
Purpura
Genes 96
MPL IFNG STIM1 TBXAS1 JAK2 NPM1 GP6 TET2 HOXA11 MYD88 GFI1B COL5A1 COL5A2 USP18 USP8 ORAI1 TREX1 FCGR2C ARL6IP6 ZBTB16 SAMD9 PRTN3 RARA ICOS GNA14 WAS COMT SEC24C WIPF1 CD19 MS4A1 SH2B3 CHST14 ARVCF P2RY12 TNFSF12 HLA-DPA1 CALR HLA-DPB1 SBDS PRF1 ETHE1 ACP5 NFKB1 NFKB2 UFD1 CD109 NUMA1 GATA1 PEPD TNFRSF13C GBA PRKAR1A TNFRSF13B ETV6 FIP1L1 PRKCD C2 CD81 PTPN22 C4A CTLA4 AIP ITGA2 ITGA2B NABP1 APOE RREB1 OCLN F2 CR2 TERC TBL1XR1 TERT ADA2 ITGB3 JMJD1C RAB27A F13A1 TBX1 NLRC4 F13B GGCX NLRP3 MVK PROC STAT5B HIRA FERMT3 GP1BA PML PROS1 GP1BB TFR2 COL1A1 GP9