RhEumatiC Heart diseAse Genetics

NCT02118818 | Completed

• 1 other identifier: 2013P002682/BWH
• Study Type: observational
• Target: 245
• Locations: 1 country
• Sites: 1

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.

Conditions

Rheumatic Heart Disease

Outcome Measures

Primary Outcomes (1)

• Echocardiographic signs of rheumatic heart disease

  All patients enrolled will have had an echocardiogram of their heart to assess for signs of rheumatic heart disease according to WHF criteria. The investigators will perform next generation sequencing on their tissue samples and perform a combination of whole exome or genotyping array on their DNA samples. The goal is to identify variants in those patients with severe disease compared to age, gender, socioeconomic, geographically matched controls without echocardiography signs of RHD.

  3 years

Study Arms (2)

NO rheumatic heart disease by echo

There will be no intervention. This is an observational trial to examine the differences in genetic variants and gene expression between patients with and without RHD. We will be using next generation sequencing to identify these differences.

Genetic: Next generation sequencing

Rheumatic heart disease by echo

There will be no intervention. This is an observational trial to examine the differences in genetic variants and gene expression between patients with and without RHD. We will be using next generation sequencing to identify these differences.

Genetic: Next generation sequencing

Interventions

Next generation sequencing GENETIC

There will be no intervention. This is an observational trial to examine the differences in genetic variants and gene expression between patients with and without RHD.

NO rheumatic heart disease by echo; Rheumatic heart disease by echo

Eligibility Criteria

• Age: 5 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

The investigators will include patients aged between 5-40 years in Rwanda presenting with an initial diagnosis of RHD and whose echocardiographic findings meet the criteria for definite RHD. World Heart Federation's criteria for echocardiographic diagnosis of definite RHD will be used, utilizing a combination of pathological criteria and morphological features.

You may qualify if:

• Clinical and echocardiographic signs of RHD using WHF criteria

You may not qualify if:

• Congenital heart disease

Sponsors & Collaborators

• Brigham and Women's Hospital: lead
• National University, Rwanda: collaborator

Study Sites (1)

University of Rwanda

Kigali, Rwanda

Location

Biospecimen

Retention: SAMPLES WITH DNA

The investigators are collecting blood for DNA analysis from all subjects as well as heart valve tissue from subjects who undergo cardiac surgery.

MeSH Terms

Conditions

Rheumatic Heart Disease

Interventions

High-Throughput Nucleotide Sequencing

Condition Hierarchy (Ancestors)

Rheumatic Fever; Streptococcal Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Sequence Analysis; Genetic Techniques; Investigative Techniques

Study Officials

• Jochen D Muehlschlegel, MD MMSc, MBA

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Target Duration: 5 Years
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Anesthesia

Study Record Dates

• First Submitted: April 15, 2014
• First Posted: April 21, 2014
• Study Start: February 1, 2014
• Primary Completion: July 1, 2024
• Study Completion: July 1, 2024
• Last Updated: August 22, 2024

Record last verified: 2024-08

Locations

RW (1)