Ignite Creation Date:
2024-05-05 @ 9:02 PM
Last Modification Date:
2024-10-26 @ 9:58 AM
Study NCT ID:
NCT00800449
Status:
COMPLETED
Last Update Posted:
2012-02-14
First Post:
2008-11-30
Brief Title:
Distribution of Haptoglobin Phenotype in Septic and Non Septic Pre-term Neonates PTSH
Sponsor:
Irina Kessel
Organization:
Carmel Medical Center
Study Overview
Official Title:
Prospective Assessment of the Distribution of Haptoglobin Phenotype in Septic and Non Septic Pre-term Neonates PTSH
Status:
COMPLETED
Status Verified Date:
2012-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The Haptoglobin Hp gene locus at chromosome 16q22 is polymorphic with two alleles denoted 1 and 2 The gene product exists in three phenotypes 1-1 2-1 and 2-2
The Haptoglobin 2 allele is found only in man and is believed to have arisen from the Haptoglobin 1 allele by a partial intragenic duplication Haptoglobin 2 allele frequency is higher than the Haptoglobin 1 allele It has been hypothesized that the Haptoglobin 2 allele was spread in man due to its selective advantage against life-threatening infections
In vitro only the Haptoglobin 2 allele protein binds to the streptococcus T antigen resulting in its aggregation and slowing its growth
Individuals homozygous for the Haptoglobin 1 allele 1-1 genotype are more prone to the streptococcal infection than individuals with the Haptoglobin 2 allele2-1 or 2-2 genotype
The investigators wish to explore the linkage between Hp phenotype and sepsis in pre-term neonates considering that in this early stage in life genetic properties which provide a defense against infectious agents will be of heightened importance
The Haptoglobin 2 allele is found only in man and is believed to have arisen from the Haptoglobin 1 allele by a partial intragenic duplication Haptoglobin 2 allele frequency is higher than the Haptoglobin 1 allele It has been hypothesized that the Haptoglobin 2 allele was spread in man due to its selective advantage against life-threatening infections
In vitro only the Haptoglobin 2 allele protein binds to the streptococcus T antigen resulting in its aggregation and slowing its growth
Individuals homozygous for the Haptoglobin 1 allele 1-1 genotype are more prone to the streptococcal infection than individuals with the Haptoglobin 2 allele2-1 or 2-2 genotype
The investigators wish to explore the linkage between Hp phenotype and sepsis in pre-term neonates considering that in this early stage in life genetic properties which provide a defense against infectious agents will be of heightened importance
Detailed Description:
The Haptoglobin Hp gene locus at chromosome 16q22 is polymorphic with two alleles denoted 1 and 2 The gene product exists in three phenotypes 1-1 2-1 and 2-2 Hp 2 allele DM individuals have larger myocardial infarctions than homozygous Hp 1 DM individuals This may be due to differences in the antioxidant and anti-inflammatory properties of these proteinsThe same phenomenon was demonstrated in a murine coronary ischemia-reperfusion model
The Haptoglobin is an acute phase protein with anti-oxidant bacteriostatic and anti-inflammatory functions
The Haptoglobin 2 allele is found only in man and is believed to have arisen from the Haptoglobin 1 allele by a partial intragenic duplication Haptoglobin 2 allele frequency is higher than the Haptoglobin 1 allele It has been hypothesized that the Haptoglobin 2 allele was spread in man due to its selective advantage against life-threatening infections
In vitro only the Haptoglobin 2 allele protein binds to the streptococcus T antigen resulting in its aggregation and slowing its growth
We proposed that in individuals homozygous for the Haptoglobin 1 allele 1-1 genotype the streptococcal infection would be more severe than in individuals with the Haptoglobin 2 allele 2-1 or 2-2 genotype
During a severe outbreak of impetigo in two infantry units in the Israeli Defense Forces over 60 5791 of the soldiers developed impetigo caused by a single pathogen-group A streptococcus 33 of them developed serious life-threatening complications requiring hospitalization The risk of Haptoglobin 1-1 genotype individuals developing severe infection was significantly higher than individuals with Haptoglobin 2 genotype 455 511 vs 175 1480 risk ratio 26 95 confidence interval 12-58 p005 This supports the notion that the Haptoglobin genotype determines the susceptibility to streptococcus infection an important pathogen early in human evolution and explains the spread of Haptoglobin 2 allele in human
Another study demonstrated that Diabetic dialysis patients at the age of 60 and above carrying the Hp1-1 phenotype had a lower mortality rate compared to the patients who are Hp2-2 However younger population has shown the opposite This can be explained by the survivorship pattern of Hp1-1 diabetic patients who have lower risk for diabetic complications They will also survive dialysis in older age by suffering less from vascular complications compared to Hp2-2 However in Hp2-2 younger patients the infectious parameter is more significant and mortality will be lower
We wish to explore the linkage between Hp phenotype and sepsis in pre-term neonates considering that in this early stage in life genetic properties which provide a defense against infectious agents will be of heightened importance
During the study period of one year all preterm neonates a total of 150 preterm babies 35 weeks or younger admitted to the preterm unit at Carmel hospital will be typed for Hp phenotype by a blood test Hp phenotyping needs only about 500 microliters of blood which will be taken during routine blood drawn All blood samples will be identified with the patients ID number and name in addition to the study consecutive serial number The blood samples will be sent to the laboratory of vascular medicine in the faculty of medicine at the Technion If the number of participating infants during one year will be insufficient less than 150 we will ask for additional permission of the ethical committee to continue the study for the second year
Septic neonates will be recognized by clinical deterioration abnormal body temperature andor disturbed skin perfusion andor apathy andor increase in apneabradycardia episodes andor abnormal CBC leukocytosis or leucopenia or left shift or thrombocytopenia and concomitant positive blood cultures without another explanation of non infectious etiology Details of the bacteria including antibiotic resistance profile will be documented Demographic data will be collected for all patients
In addition data regarding known pre-maturity complications such as Retinopathy of Pre-maturity ROP Necrotizing Entero-Colitis NEC Broncho-Pulmonary Dysplasia BPD will be assessed and documented according to the admission summary
Blood transport Hp typing and data collection will be done by a MD student as part of her MD thesis
As part of the informed consent we will ask the permission for a possible follow up one year after discharge from the hospital which will be done by a phone questionnaire and acquiring the patients medical file data with the help of his family
The Haptoglobin is an acute phase protein with anti-oxidant bacteriostatic and anti-inflammatory functions
The Haptoglobin 2 allele is found only in man and is believed to have arisen from the Haptoglobin 1 allele by a partial intragenic duplication Haptoglobin 2 allele frequency is higher than the Haptoglobin 1 allele It has been hypothesized that the Haptoglobin 2 allele was spread in man due to its selective advantage against life-threatening infections
In vitro only the Haptoglobin 2 allele protein binds to the streptococcus T antigen resulting in its aggregation and slowing its growth
We proposed that in individuals homozygous for the Haptoglobin 1 allele 1-1 genotype the streptococcal infection would be more severe than in individuals with the Haptoglobin 2 allele 2-1 or 2-2 genotype
During a severe outbreak of impetigo in two infantry units in the Israeli Defense Forces over 60 5791 of the soldiers developed impetigo caused by a single pathogen-group A streptococcus 33 of them developed serious life-threatening complications requiring hospitalization The risk of Haptoglobin 1-1 genotype individuals developing severe infection was significantly higher than individuals with Haptoglobin 2 genotype 455 511 vs 175 1480 risk ratio 26 95 confidence interval 12-58 p005 This supports the notion that the Haptoglobin genotype determines the susceptibility to streptococcus infection an important pathogen early in human evolution and explains the spread of Haptoglobin 2 allele in human
Another study demonstrated that Diabetic dialysis patients at the age of 60 and above carrying the Hp1-1 phenotype had a lower mortality rate compared to the patients who are Hp2-2 However younger population has shown the opposite This can be explained by the survivorship pattern of Hp1-1 diabetic patients who have lower risk for diabetic complications They will also survive dialysis in older age by suffering less from vascular complications compared to Hp2-2 However in Hp2-2 younger patients the infectious parameter is more significant and mortality will be lower
We wish to explore the linkage between Hp phenotype and sepsis in pre-term neonates considering that in this early stage in life genetic properties which provide a defense against infectious agents will be of heightened importance
During the study period of one year all preterm neonates a total of 150 preterm babies 35 weeks or younger admitted to the preterm unit at Carmel hospital will be typed for Hp phenotype by a blood test Hp phenotyping needs only about 500 microliters of blood which will be taken during routine blood drawn All blood samples will be identified with the patients ID number and name in addition to the study consecutive serial number The blood samples will be sent to the laboratory of vascular medicine in the faculty of medicine at the Technion If the number of participating infants during one year will be insufficient less than 150 we will ask for additional permission of the ethical committee to continue the study for the second year
Septic neonates will be recognized by clinical deterioration abnormal body temperature andor disturbed skin perfusion andor apathy andor increase in apneabradycardia episodes andor abnormal CBC leukocytosis or leucopenia or left shift or thrombocytopenia and concomitant positive blood cultures without another explanation of non infectious etiology Details of the bacteria including antibiotic resistance profile will be documented Demographic data will be collected for all patients
In addition data regarding known pre-maturity complications such as Retinopathy of Pre-maturity ROP Necrotizing Entero-Colitis NEC Broncho-Pulmonary Dysplasia BPD will be assessed and documented according to the admission summary
Blood transport Hp typing and data collection will be done by a MD student as part of her MD thesis
As part of the informed consent we will ask the permission for a possible follow up one year after discharge from the hospital which will be done by a phone questionnaire and acquiring the patients medical file data with the help of his family
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