SNPMiner Trials by Shray Alag


SNPMiner Trials: Clinical Trial Report


Report for Clinical Trial NCT01120964

Developed by Shray Alag, 2019.
SNP Clinical Trial Gene

Phase IB Double Blind, Randomized, Placebo Controlled Clinical Trial to Determine the Pharmacokinetics and Safety of a Revised Protocol of Intravenous L-Citrulline (Citrupress®) Versus Placebo in Children Undergoing Cardiopulmonary Bypass

This clinical trial will determine the safety and effectiveness of intravenous L-citrulline in children undergoing cardiopulmonary bypass during heart surgery. Participants will be randomly assigned to either L-citrulline or a placebo (a substance that has no medicine in it). Citrulline is a protein building block in the body that can convert into another substance, nitric oxide (NO), which controls blood pressure in the lungs. Increased blood pressure in the lungs can be an important surgical problem; it may also lead to problems following surgery, such as severe high blood pressure in the lungs (pulmonary hypertension), increased time spent on a breathing machine, and a longer stay in the intensive care unit (ICU). The hypothesis of this study is that perioperative supplementation with intravenous citrulline will increase plasma citrulline, arginine and NO metabolites and prevent elevations in the postoperative PVT leading to a decrease in the duration of postoperative invasive mechanical ventilation. The objective of this study is to determine in a randomized placebo controlled phase IB multicenter clinical trial if a revised protocol of intravenous L-citrulline delivery given perioperatively achieves a plasma citrulline level of > 100 umol/L in children undergoing surgical repair of an atrial septal defect,ventricular septal defect or an atrioventricular septal defect.

NCT01120964 Atrial Septal Defect Ventricular Septal Defect Atrioventricular Septal Defect
MeSH: Heart Septal Defects Heart Septal Defects, Ventricular Heart Septal Defects, Atrial Endocardial Cushion Defects
HPO: Abnormal cardiac septum morphology Atrial septal defect Atrioventricular canal defect Secundum atrial septal defect Ventricular septal defect

2 Interventions

Name: Intravenous L-Citrulline

Description: 150mg bolus X 1 after initiation of cardiopulmonary bypass, the addition of L-citrulline at a concentration of 200 umol/L or placebo to the filtration and hemoconcentration fluid utilized during cardiopulmonary bypass in addition to a 20mg/kg bolus 30 minutes after separation from cardiopulmonary bypass immediately followed by a continuous infusion of 9mg/kg/hr IV, and ending at 48 hours continuous infusion or discharge from the PCCU.

Type: Drug

Intravenous L-Citrulline

Name: Placebo of Intravenous L-Citrulline

Description: Placebo of Intravenous L-Citrulline given at the same prescribed times as L-Citrullne Drug

Type: Drug

Placebo of Intravenous L-Citrulline


Primary Outcomes

Description: Citrulline Blood Levels : 1. Baseline sample in OR prior to Cardiopulmonary Bypass prior to admistration of first bolus of Citrulline or Placebo 2. Immediately after Bolus 1 administered in Operating Room. 3. 30 minutes after separation from Cardiopulmonary Bypass; immediately prior to administration of Bolus 2 and start of continuous infusion of Citrulline or Placebo. 4. Six hours after after start of infusion. 5. 12 hours after start of infusion. 6. 24 hours after start of infusion. 7. 48 hours after start of infusion; or whenever infususion is discontinued if prior to 48 hours.

Measure: To determine if L-citrulline given perioperatively achieves a plasma citrulline level of > 100 umol/L in children undergoing surgical repair of an atrial septal defect, a ventricular septal defect or an atrioventricular septal defect.

Time: Measured in seven blood sample time points from the beginning of surgery until end of IV Citrulline Infusion; at either 48 hours postoperatively or at extubation, whichever comes first.

Secondary Outcomes

Measure: Duration of postoperative mechanical ventilation in hours compared between treatment groups

Time: Measured in hours from the end of surgery until extubation

Measure: Incidence of increased PVT (defined as a sustained mean pulmonary artery pressure greater than 20 mm Hg for at least 2 hours, measured during the first 48 hours

Time: Measured in hours from the end of surgery until extubation

Measure: Postoperative intravenous inotrope score

Time: Measured at 48 hours

Measure: Length and volume of chest tube drainage

Time: Measured in hours from the end of surgery until removal of chest tubes

Measure: Length of ICU stay

Time: Measured in hours from the end of surgery to discharge from ICU

Measure: Length of hospitalization

Time: Measured from the day of surgery until discharge from hospital

Measure: Survival

Time: Measured at 28 days post surgical repair

Description: Age specific mean aterial blood pressrue limits compared between the citrulline and placebo groups will be used to determine significant hypotension.

Measure: The incidence of clinically significant hypotension.

Time: Mean Arterial Blood pressure as continuously monitored postoperatively in the PCCU during Citrulline or Placebo infusion.

Purpose: Prevention

Allocation: Randomized

Parallel Assignment


There is one SNP

SNPs


1 T1405N

Finally, a genetic single nucleotide polymorphism (SNP) in the rate limiting urea cycle enzyme (carbamyl phosphate synthetase I [CPSl T1405N]) appeared to affect postoperative plasma arginine levels and PVT. --- T1405N ---



HPO Nodes


HPO:
Abnormal cardiac septum morphology
Genes 462
EPHB4 MKKS TACO1 PIGN RPL27 ASXL1 ERBB3 CTU2 SLC29A3 ERCC2 RPL35A DGCR6 SF3B4 AMER1 ERCC3 BRIP1 LZTR1 ERCC4 ABL1 IRX5 ESS2 ZMPSTE24 PDHA1 CWC27 DNAJC19 CCDC174 USP9X SMC1A TRAIP APC2 GDF6 NAA10 PEX1 ACTC1 PEX6 PEX10 EVC MMP21 PEX12 PEX13 RPS17 PEX14 RPS19 CHD4 EXT2 RPS26 WNT4 ACVR2B RREB1 TRIP13 LYST CHRM3 TRIP4 MEIS2 HNRNPU HIRA RNU4ATAC CDC45 MEOX1 EFTUD2 FANCA FANCC FANCD2 CITED2 FANCE ADK HOXA13 CRELD1 FANCB DACT1 FANCF FANCG LONP1 ARID1B MGAT2 FBN1 FBN2 SALL1 PIGA MGP HOXD13 ARHGAP31 FKTN PIK3CA STRADA PIK3R2 JAG1 RECQL4 UFD1 GPC4 PEX16 HRAS WDR35 GTF2H5 KMT2A ALG8 UMPS PLAGL1 FGFR1 FGFR3 FGFR2 DGCR8 PLD1 MAD2L2 FTO TMCO1 LTBP4 KDM6A NIPBL ALG12 HSPA9 DSE SDHA FOXF1 FOXC1 CHST3 COL1A1 FOXC2 MPL SLC25A24 COL5A1 FLI1 COL5A2 HSPG2 NDUFB11 FLNA FLNB PIGL FOXRED1 COL11A1 COL11A2 TBX4 CCDC22 NDUFAF5 POLR1A ANK1 COMT TAPT1 CLIP2 DLL4 PTF1A PUF60 WHCR NSD2 NELFA IFT81 PEX3 CEP290 ARX SLC19A2 KCNAB2 WT1 COX7B POR PORCN COX15 CHD7 GATA5 XRCC2 FANCM GTF2IRD1 SKI GDF3 CREBBP CDK10 SHANK3 SH2B1 ARCN1 PEX26 CRKL STAMBP ZIC3 PPP1CB MTFMT PACS1 PPP2CA SETD2 LIPT1 VAC14 IGBP1 VIPAS39 NPHP3 PIEZO2 IGF1R KANSL1 SEC24C UBE2T G6PC3 ARVCF CTCF DYNC2LI1 CDK13 OTUD6B TP63 TTC37 SETBP1 ANKRD11 MPLKIP RSPO2 FLCN NKX2-5 SMARCE1 SMN1 CTBP1 NDUFAF6 ATIC RERE MAPK1 FUT8 MAP2K1 SNRPB MAP2K2 CEP57 MCTP2 PRDM16 STAG2 SLX4 AFF4 CRB2 SEMA3E SON SOS1 SOS2 SOX2 RAB23 GABRD UBR1 ATP6V1A TCTN3 KDM5B INTU MYH6 MASP1 ATP6V1E1 MYH7 NDUFS7 EOGT MYL2 ATRX CHST14 TMEM94 PET100 IFT172 PIEZO1 PKD1L1 RNF113A KIAA0586 HDAC8 GATA1 CPLX1 GATA4 GATA6 FADD BBS2 FGFRL1 TAB2 NKX2-6 UPF3B PSMD12 NDUFA2 NDUFA4 PEX11B SRCAP NDUFA9 PTEN BCOR GDF1 NDUFA10 BCR NEK9 ZEB2 NDUFS1 NDUFS2 NDUFS3 PHGDH NDUFV1 NDUFS4 STAT1 B3GAT3 MKS1 NDUFS8 NDUFV2 NSDHL DDX11 XYLT1 TMEM260 XYLT2 STK4 GJA1 BMP2 NEK1 BMPR1A PTPN11 TXNL4A NF1 GLA GPC3 NDUFA12 BRCA1 BRAF BRCA2 VPS33B CANT1 FIG4 WASHC5 NFE2L2 GLI1 NFIX GLI3 SURF1 DHCR7 MYPN BUB1 BUB1B CFC1 PEX19 ABCD4 PEX2 MYMK PEX5 SMG9 HYLS1 PACS2 RBM8A STRA6 AMMECR1 TBX20 MAP3K7 HYMAI NODAL TALDO1 MYRF NONO MED12 PIGO NOTCH1 TBX1 NOTCH2 NOTCH3 KIF11 DNMT3A GP1BB RAD21 TBX2 TBX5 RAD51 TBX22 RAD51C KRAS RAF1 CACNA1C CACNA1D DGCR2 DPH1 TBX3 AKT3 RAP1A RAP1B EVC2 B3GLCT RARB NUP107 DSG1 NDUFAF2 DTNA SYNE1 UBE3B ROR2 KAT6A GPX4 ASCC1 DVL3 SLC19A3 NSD1 AGGF1 BAZ1B WDR60 B3GALT6 SALL4 FANCL SPECC1L DPF2 LBR SIK3 MED13L RFC2 ECE1 GPC6 CCNQ LARS2 PQBP1 ECHS1 SHOC2 NXN TFAP2B JMJD1C WDPCP PALB2 LETM1 NR2F2 TSFM RFWD3 KIF7 CCND2 SIX6 ESCO2 RIT1 TTC7A TGFB3 ADAMTS10 TGFBR1 NDUFA13 RMRP TGFBR2 MLXIPL LIMK1 GTF2E2 KMT2D GTF2I LMNA MEGF8 SMC3 NKX2-1 SETD5 ZDHHC9 TKT CCBE1 FANCI GYG1 ARID2 TLL1 ALG9 TGDS PAH MED25 LRP2 EHMT1 FIBP CKAP2L LRP5 HAAO YY1AP1 BSCL2 ASXL2 LTBP2 PAX3 ELN BUB3 KAT6B CDC42 HCCS RPL5 TBL2 CD96 EP300 VPS13B RPL10 RPL11 SMAD4 ATP6V0A2 RPL15 PCNT
Atrial septal defect
Genes 281
EPHB4 MKKS RAB23 PIGN UBR1 ATP6V1A RPL27 KDM5B ASXL1 MYH6 MASP1 ATP6V1E1 CTU2 MYH7 SLC29A3 AMER1 BRIP1 EOGT ERCC4 ABL1 IRX5 ZMPSTE24 CHST14 TMEM94 USP9X SMC1A PIEZO1 TRAIP KIAA0586 HDAC8 CPLX1 GATA4 GATA6 NAA10 ACTC1 BBS2 EVC MMP21 FGFRL1 RPS17 RPS19 CHD4 UPF3B SRCAP RREB1 PTEN BCOR GDF1 BCR TRIP13 LYST CHRM3 NEK9 TRIP4 ZEB2 PHGDH MEIS2 STAT1 B3GAT3 HIRA RNU4ATAC CDC45 EFTUD2 FANCA FANCC FANCD2 CITED2 FANCE ADK TMEM260 XYLT2 STK4 GJA1 BMP2 FANCB DACT1 FANCF FANCG NEK1 BMPR1A LONP1 ARID1B PTPN11 FBN2 TXNL4A NF1 SALL1 PIGA GPC3 BRCA1 BRAF BRCA2 VPS33B FIG4 WASHC5 ARHGAP31 FKTN NFE2L2 STRADA GLI1 NFIX PIK3R2 GLI3 DHCR7 JAG1 UFD1 BUB1 BUB1B GPC4 PEX19 HRAS ABCD4 WDR35 KMT2A UMPS RBM8A FGFR1 FGFR3 FGFR2 PLD1 MAD2L2 STRA6 AMMECR1 TBX20 TMCO1 MAP3K7 NODAL TALDO1 LTBP4 MYRF NONO KDM6A NIPBL ALG12 MED12 PIGO HSPA9 NOTCH1 TBX1 DSE NOTCH2 FOXF1 FOXC1 KIF11 DNMT3A GP1BB CHST3 COL1A1 RAD21 TBX2 TBX5 RAD51 TBX22 RAD51C KRAS SLC25A24 RAF1 CACNA1C CACNA1D COL5A1 COL5A2 HSPG2 NDUFB11 FLNB COL11A1 EVC2 B3GLCT TBX4 CCDC22 ANK1 COMT CLIP2 PTF1A WHCR NSD2 NELFA UBE3B ROR2 CEP290 KAT6A GPX4 ASCC1 SLC19A2 DVL3 WT1 NSD1 COX7B AGGF1 BAZ1B POR B3GALT6 SALL4 FANCL CHD7 GATA5 SPECC1L SIK3 XRCC2 MED13L RFC2 FANCM GTF2IRD1 ECE1 GPC6 PQBP1 SHOC2 NXN CREBBP CDK10 JMJD1C PALB2 SH2B1 LETM1 TSFM CRKL RFWD3 STAMBP ZIC3 PPP1CB ESCO2 RIT1 TGFB3 TGFBR1 TGFBR2 PACS1 MLXIPL LIMK1 VAC14 KMT2D NPHP3 IGF1R GTF2I KANSL1 SEC24C LMNA UBE2T MEGF8 G6PC3 ARVCF SMC3 CTCF NKX2-1 SETD5 ZDHHC9 DYNC2LI1 CDK13 TKT CCBE1 FANCI OTUD6B ARID2 TLL1 SETBP1 TGDS FLCN NKX2-5 HAAO SMARCE1 SMN1 CTBP1 ASXL2 PAX3 ELN ATIC MAPK1 BUB3 KAT6B MAP2K1 SNRPB MAP2K2 CEP57 HCCS RPL5 TBL2 EP300 SLX4 RPL11 SMAD4 SEMA3E SON PCNT
Atrioventricular canal defect
Genes 40
GATA4 GATA6 RAF1 HYLS1 EVC GJA1 MMP21 NKX2-5 CRELD1 FANCB FLNA NEK1 INTU LONP1 NKX2-6 PTPN11 EVC2 CCDC22 ACVR2B BRAF GDF1 KAT6B MAP3K7 WASHC5 DYNC2LI1 PUF60 KDM6A GLI1 WDPCP GLI3 NR2F2 TBX1 DHCR7 FOXF1 PKD1L1 ZIC3 CFC1 CDC45 TBX5 GATA1
Secundum atrial septal defect
Genes 9
MYH6 GDF1 GATA6 RPL11 NKX2-5 PTF1A NF1 TRIP4 TBX5
Ventricular septal defect
Genes 294
SOX2 MKKS RAB23 TACO1 UBR1 TCTN3 ASXL1 MASP1 ERBB3 CTU2 SLC29A3 ERCC2 RPL35A DGCR6 SF3B4 NDUFS7 AMER1 ERCC3 EOGT ABL1 ESS2 ATRX PDHA1 CWC27 DNAJC19 TMEM94 CCDC174 PET100 IFT172 SMC1A TRAIP PKD1L1 RNF113A GDF6 HDAC8 CPLX1 GATA4 GATA6 NAA10 FADD PEX1 PEX6 PEX10 EVC PEX12 FGFRL1 PEX13 PEX14 TAB2 RPS19 CHD4 EXT2 NDUFA2 RPS26 NDUFA4 WNT4 ACVR2B PEX11B RREB1 NDUFA9 BCOR GDF1 NDUFA10 BCR CHRM3 NEK9 ZEB2 NDUFS1 NDUFS2 NDUFS3 PHGDH NDUFV1 MEIS2 NDUFS4 NDUFS8 NDUFV2 HIRA RNU4ATAC CDC45 MEOX1 EFTUD2 DDX11 CITED2 XYLT1 TMEM260 XYLT2 GJA1 HOXA13 BMP2 NEK1 LONP1 ARID1B PTPN11 MGAT2 FBN1 FBN2 TXNL4A SALL1 GPC3 NDUFA12 MGP BRAF VPS33B CANT1 FIG4 WASHC5 ARHGAP31 PIK3CA GLI1 PIK3R2 GLI3 SURF1 DHCR7 JAG1 UFD1 GPC4 PEX19 PEX16 HRAS PEX2 GTF2H5 PEX5 SMG9 HYLS1 KMT2A UMPS PLAGL1 RBM8A FGFR1 FGFR2 DGCR8 STRA6 FTO HYMAI NODAL TALDO1 MYRF NONO KDM6A NIPBL MED12 TBX1 NOTCH2 SDHA FOXF1 NOTCH3 GP1BB CHST3 RAD21 TBX5 FOXC2 KRAS CACNA1C CACNA1D DGCR2 DPH1 FLI1 NDUFB11 FLNB TBX3 PIGL AKT3 FOXRED1 COL11A2 EVC2 B3GLCT CCDC22 RARB NDUFAF5 COMT TAPT1 NUP107 DSG1 CLIP2 NDUFAF2 DLL4 PUF60 WHCR NSD2 DTNA IFT81 UBE3B PEX3 ROR2 CEP290 KAT6A ARX SLC19A2 DVL3 SLC19A3 WT1 NSD1 COX7B BAZ1B WDR60 PORCN B3GALT6 COX15 SALL4 CHD7 GATA5 SPECC1L LBR RFC2 GTF2IRD1 ECE1 GPC6 LARS2 PQBP1 ECHS1 SHOC2 GDF3 NXN CREBBP TFAP2B JMJD1C SHANK3 PALB2 LETM1 NR2F2 ARCN1 PEX26 CRKL STAMBP ZIC3 PPP1CB MTFMT CCND2 SIX6 ESCO2 RIT1 TTC7A TGFB3 ADAMTS10 NDUFA13 MLXIPL LIMK1 LIPT1 GTF2E2 VAC14 IGBP1 KMT2D VIPAS39 PIEZO2 IGF1R GTF2I KANSL1 SEC24C ARVCF SMC3 NKX2-1 SETD5 DYNC2LI1 CDK13 TKT CCBE1 FANCI OTUD6B TP63 TTC37 TGDS PAH ANKRD11 LRP2 MPLKIP FIBP CKAP2L RSPO2 LRP5 NKX2-5 SMN1 CTBP1 NDUFAF6 YY1AP1 LTBP2 ELN RERE MAPK1 KAT6B MAP2K1 SNRPB CEP57 HCCS RPL5 TBL2 CD96 EP300 VPS13B RPL11 CRB2 SMAD4 RPL15 SEMA3E SOS1