Ignite Creation Date:
2024-05-06 @ 2:44 AM
Last Modification Date:
2024-10-26 @ 11:23 AM
Study NCT ID:
NCT02118818
Status:
COMPLETED
Last Update Posted:
2023-02-08
First Post:
2014-04-15
Brief Title:
RhEumatiC Heart diseAse Genetics
Sponsor:
Brigham and Womens Hospital
Organization:
Brigham and Womens Hospital
Study Overview
Official Title:
Next Generation Sequencing Approach to the Study of Rheumatic Heart Disease
Status:
COMPLETED
Status Verified Date:
2024-08
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:
RECHARGE
Brief Summary:
Rheumatic fever RF is an autoimmune disease that is mediated by the cellular and humoral immune response that follows an untreated pharyngeal Streptococcus pyogenes infection The most serious complication is rheumatic heart disease RHD one of the most common problems facing children and young adults worldwide which leads to chronic valvular lesions It is estimated that 60 of all acute rheumatic fever cases will develop RHD
The pathogenesis of RHD is complex with both environmental and genetic factors contributing to its etiology The investigators know little about the genetic etiology cellular events and modifiers of progression of RHD and there exists a wide range of disease severity and progression to severe valve pathology
Thus the investigators will study the genetics of RHD in Rwanda a country with a very high incidence of RHD using a combination of next-generation targeted exome capture transcriptomics and expressed quantitative trait loci eQTL analysis
The pathogenesis of RHD is complex with both environmental and genetic factors contributing to its etiology The investigators know little about the genetic etiology cellular events and modifiers of progression of RHD and there exists a wide range of disease severity and progression to severe valve pathology
Thus the investigators will study the genetics of RHD in Rwanda a country with a very high incidence of RHD using a combination of next-generation targeted exome capture transcriptomics and expressed quantitative trait loci eQTL analysis
Detailed Description:
There are an estimated 24 million children between 5 and 14 years of age affected by RF andor RHD in developing countries of the world approximately one million of whom live in sub-Saharan Africa 40 1 A systematic review of prevalence studies found exceptionally high rates of RHD in sub-Saharan Africa with the highest level found at 304 cases per 1000 children in Mozambique 2345 At present no specific treatment for rheumatic heart disease exists other than for its complications including heart failure atrial fibrillation ischemic embolic events and infective endocarditis Medical treatment other than antibiotic prophylaxis has shown little evidence of slowing the progression of the disease Medical heart failure treatment is given when patients become symptomatic and includes mainly β blockers angiotensin converting- enzyme inhibitor therapies or a combination of both as tolerated and symptomatic treatments such as diuretics Patients with atrial fibrillation need rate or rhythm control and anticoagulation with warfarin if at high risk of embolic complications Rheumatic heart disease is a major cause of infective endocarditis in African countries
North American and European guidelines have considerably reduced the number of heart disorders needing antibiotic prophylaxis to prevent infective endocarditis Whether guidelines issued from developed regions can be safely applied to developing countries is debatable and further studies are warranted Pregnancy in patients with rheumatic heart disease is a challenge and is associated with high morbidity and mortality Antenatal consultation with support from cardiology and obstetrics clinics should be done to Provide contraception counseling treatment planning before start of pregnancy and planning for patients with moderate to severe disease who are already pregnant eg caesarean section
Rheumatic fever RF is an autoimmune disease that is mediated by the cellular and humoral immune response that follows an untreated pharyngeal Streptococcus pyogenes infection The most serious complication is rheumatic heart disease RHD one of the most common problems facing children and young adults worldwide which leads to chronic valvular lesions It is estimated that 60 of all acute rheumatic fever cases will develop RHD Each year there are 280000 new cases and almost as many deaths from RHD with a worldwide prevalence of 15 million of which almost 20 are children aged 5-14 years The worldwide mortality from RHD is 15 annually compared with an overall mortality of 026 for all other cardiovascular diseases in the US3 79 of all RHD cases come from less developed countries with the highest prevalence in sub-Saharan Africa and Pacific and indigenous AustraliaNew Zealand 3-7 cases per 1000
The pathogenesis of RHD is complex with both environmental and genetic factors contributing to its etiology though molecular mimicry between components of S pyogenes and human heart tissue appear to be a central problem A clear correlation exists between disease prevalence and lower socioeconomic status in developing countries while the disease prevalence in developed countries continues to decline However the manifestation of acute rheumatic fever in only a subset of children with untreated throat infection by S pyogenes familial clustering and high concordance of RHD among monozygous twins provides strong evidence for genetic determinants for disease susceptibility Yet the investigators know little about the genetic etiology cellular events and modifiers of progression of RHD and there exists a wide range of disease severity and progression to severe valve pathology
North American and European guidelines have considerably reduced the number of heart disorders needing antibiotic prophylaxis to prevent infective endocarditis Whether guidelines issued from developed regions can be safely applied to developing countries is debatable and further studies are warranted Pregnancy in patients with rheumatic heart disease is a challenge and is associated with high morbidity and mortality Antenatal consultation with support from cardiology and obstetrics clinics should be done to Provide contraception counseling treatment planning before start of pregnancy and planning for patients with moderate to severe disease who are already pregnant eg caesarean section
Rheumatic fever RF is an autoimmune disease that is mediated by the cellular and humoral immune response that follows an untreated pharyngeal Streptococcus pyogenes infection The most serious complication is rheumatic heart disease RHD one of the most common problems facing children and young adults worldwide which leads to chronic valvular lesions It is estimated that 60 of all acute rheumatic fever cases will develop RHD Each year there are 280000 new cases and almost as many deaths from RHD with a worldwide prevalence of 15 million of which almost 20 are children aged 5-14 years The worldwide mortality from RHD is 15 annually compared with an overall mortality of 026 for all other cardiovascular diseases in the US3 79 of all RHD cases come from less developed countries with the highest prevalence in sub-Saharan Africa and Pacific and indigenous AustraliaNew Zealand 3-7 cases per 1000
The pathogenesis of RHD is complex with both environmental and genetic factors contributing to its etiology though molecular mimicry between components of S pyogenes and human heart tissue appear to be a central problem A clear correlation exists between disease prevalence and lower socioeconomic status in developing countries while the disease prevalence in developed countries continues to decline However the manifestation of acute rheumatic fever in only a subset of children with untreated throat infection by S pyogenes familial clustering and high concordance of RHD among monozygous twins provides strong evidence for genetic determinants for disease susceptibility Yet the investigators know little about the genetic etiology cellular events and modifiers of progression of RHD and there exists a wide range of disease severity and progression to severe valve pathology
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