SNPMiner Trials (Home Page)
Report for Mutation T1405N
Developed by Shray Alag, 2020.
SNP Clinical Trial Gene
There are 4 clinical trials
Clinical Trials
1 Phase I/II Clinical Trial to Determine the Pharmacokinetics and Safety Profile of Citrulline in Children Undergoing Cardiopulmonary Bypass
This study will determine the pharmacokinetics and safety of intravenous citrulline given to children undergoing cardiopulmonary bypass for the correction of congenital heart defects.
NCT00201214 Cardiovascular Diseases Heart Diseases Heart Defects, Congenital Drug: Citrulline MeSH:Heart Diseases Heart Defects, Congenital Congenital Abnormalities Cardiovascular Diseases
HPO:Abnormal heart morphology Abnormality of the cardiovascular system
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 ---
Primary Outcomes
Measure: Oxygen index (OI) data to assess increased PVT Time: Measured through the use of continuous mean arterial pressure monitoringMeasure: Qp:Qs ratios to assess increased PVT Time: Measured by blood gases collected 48 hours post-operative
Measure: Increased PVT as measured by a sustained mean pulmonary artery pressure greater than 20 mm Hg for at least 2 hours during the first 24 hours postoperatively Time: Measured through the use of continuous mean arterial pressure monitoring 48 hours post-operative
2 A Phase III Single-Blind, Randomized, Placebo Controlled, Clinical Trial to Determine the Safety and Efficacy of Intravenous L-Citrulline 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.
NCT00335244 Heart Defects, Congenital Hypertension, Pulmonary Drug: L-citrulline Drug: Placebo of intravenous L-citrulline MeSH:Hypertension, Pulmonary Heart Defects, Congenital Congenital Ab Congenital Abnormalities
HPO:Abnormal heart morphology Pulmonary arterial hypertension
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 ---
Primary Outcomes
Measure: Duration of postoperative mechanical ventilation in hours compared between treatment groups. Time: Measured in hours from the end of surgery until extubationSecondary Outcomes
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 extubationMeasure: 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 30 days post surgical repair
3 Carbamoyl-phosphate Synthase Gene Polymorphisms Influencing Plasma L-arginine Concentrations in Preterm Infants
Plasma L-arginine concentrations are decreased in premature infants with necrotizing enterocolitis (NEC). A carbamoyl-phosphate synthetase 1 (CPS1) polymorphism has been correlated with low plasma concentrations of L-arginine in neonates (> 35 weeks of gestation). Recently Moonen et al (Pediatr Res 2007; 62(2):188-90) described a correlation between this CPS1 T1405N single nucleotide polymorphism (SNP) and the presence of NEC in VLBW infants. However there is no data about the correlation between the plasma arginine concentrations and the T1405N SNP in the CPS-1 gene in VLBW infants. In the present project we postulate that T1405N SNP in the CPS-1 gene is associated with lower plasma arginine concentrations and is also a risk factor for the development of NEC.
NCT00554866 Infant, Very Low Birth Weight Other: blood sample and buccal swab sample MeSH:Birth Weight
Recently Moonen et al (Pediatr Res 2007; 62(2):188-90) described a correlation between this CPS1 T1405N single nucleotide polymorphism (SNP) and the presence of NEC in VLBW infants. --- T1405N ---
However there is no data about the correlation between the plasma arginine concentrations and the T1405N SNP in the CPS-1 gene in VLBW infants. --- T1405N ---
In the present project we postulate that T1405N SNP in the CPS-1 gene is associated with lower plasma arginine concentrations and is also a risk factor for the development of NEC. the association between the T1405N SNP in the CPS-1 gene and lower plasma L-arginine concentrations. --- T1405N ---
In the present project we postulate that T1405N SNP in the CPS-1 gene is associated with lower plasma arginine concentrations and is also a risk factor for the development of NEC. the association between the T1405N SNP in the CPS-1 gene and lower plasma L-arginine concentrations. --- T1405N --- --- T1405N ---
To determine whether the T1405N SNP in the CPS-1 gene is associated with a higher risk of NEC. --- T1405N ---
A C-to-A nucleotide transversion (T1405N) in the gene that encodes carbamoyl-phosphate synthetase 1 (CPS1), the rate-limiting enzyme in the urea cycle, has been correlated with low plasma concentrations of L-arginine in neonates (> 35 weeks of gestation). --- T1405N ---
In the present project we postulate that T1405N SNP in the CPS-1 gene is associated with lower plasma arginine concentrations and is also a risk factor for the development of NEC. --- T1405N ---
Primary Outcomes
Measure: the association between the T1405N SNP in the CPS-1 gene and lower plasma L-arginine concentrations Time: 2 yearsSecondary Outcomes
Measure: To determine whether the T1405N SNP in the CPS-1 gene is associated with a higher risk of NEC Time: 4 years4 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 Atrioventricular Septal Defect Drug: Intravenous L-Citrulline Drug: Placebo of Intravenous L-Citrulline 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
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 ---
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 extubationMeasure: 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.