NIAID Centralized Sequencing Protocol

Primary Immunodeficiency Clinical Trial

Official title: NIAID Centralized Sequencing Protocol

Status Recruiting

Clinical Trial Summary

Background:

Genetic testing called "sequencing" helps researchers look at DNA. Genes are made of DNA and are the instructions for our bodies to function. We all have thousands of genes. DNA variants are differences in genes between two people. We all have lots of variants. Most are harmless and some cause differences like blue or brown eyes. A few variants can cause health problems.

Objective:

To understand the genetics of immune disorders various health conditions, as well as outcomes of clinical genomics and genetic counseling services performed under this protocol.

Eligibility:

Participants in other NIH human subjects research protocols - either at the NIH Clinical Center (CC) or at Children s National Health System (CNHS) - (aged 0-99 years), and, in select cases, their biological relatives

Design:

Researchers will study participant s DNA extracted from blood, saliva, or another tissue sample, including previously collected samples we may have stored at the NIH. Researchers will look at participant s DNA in great detail. We are looking for differences in the DNA sequence or structure between participants and other people.

Participants will receive results that:

• Are important to their health

• Have been confirmed in a clinical lab

• Suggest that they could be at risk for serious disease that may affect your current or future medical management.

Some genetic information we return to participants may be of uncertain importance.

If genetic test results are unrelated to the participant s NIH evaluations, then we will not typically report:

• Normal variants

• Information about progressive, fatal conditions that have no effective treatment

• Carrier status (conditions you don t have but could pass on)

The samples and data will be saved for future research.

Personal data will be kept as private as possible.

If future studies need new information, participants may be contacted.

Clinical Trial Description

Study Design: This study serves as a centralized sequencing protocol for NIH human subjects research studies to facilitate standardization and consolidate accrual of genotype and phenotype data for participating programs. Participants of other NIH studies both at the NIH CC and CNHS that include genetic testing may enroll in this protocol and genetic testing will be conducted under this

study.

Objective: Primary: To generate and analyze evidence regarding the genetic contribution to diverse immune diseases and other health

conditions studied by the NIH intramural research program (IRP).

Secondary: To generate and analyze evidence regarding the processes and outcomes of the clinical genomics and genetic

counseling services performed under this protocol.

Endpoint: Primary: Discrete genetic contributions to immune diseases and other health conditions, explicitly including:

Established genetic disorders.

Novel genetic defects.

Novel phenotypes associated with established genetic

disorders.

Secondary: Evidence base for how to improve clinical genomic services on this protocol and related programs.

PRECIS

Investigators at the National Institute of Allergy and Infectious Diseases (NIAID) use next-generation sequencing technologies to help determine genetic contributions to immune diseases. These efforts have increased rates of molecular diagnosis for a subset of NIAID

participants as well as uncovered fundamental insights into the cellular and signaling pathways in host defense and immune regulation.

Despite these successes, analysis and interpretation of genomic data remain a substantial challenge. Simply, researchers do not understand the functional and clinical consequences of most human genetic variation. This is true at NIAID and across the intramural research program. Making progress in this area requires a coordinated, systematic, and transparent approach to

clinical genomics research.

This protocol is specific to genetic testing and explicitly aims to both strengthen clinical care and enhance research throughout participating programs at the NIH. Probands will provide biological specimens for genetic testing and will be required to be enrolled on a primary protocol, which will execute the primary clinical and research evaluations. This protocol serves as a vehicle for a

programmatic effort that includes standardized phenotyping, test ordering through the Clinical Research Information System (CRIS), sample collection and isolation, nucleic acid analysis, bioinformatics, clinical interpretation, reporting in CRIS, genetic counseling, and supporting effective use of genomics as a research tool throughout the intramural program. Genetic testing results and data (upon request) will be shared with the research teams for protocols on which a given participant is co-enrolled. Overall, increased process standardization will support data integrity and efficiency while still accommodating the need for investigator flexibility. ;

Related Conditions & MeSH terms

• Atopy
• Autoimmunity
• Autoinflammation
• Primary Immunodeficiency
• Primary Immunodeficiency Diseases

• NCT number: NCT03206099
• Study type: Observational
• Source: National Institutes of Health Clinical Center (CC)
• Contact: Morgan N Similuk
• Phone: (301) 435-6691
• Email: morgan.similuk@nih.gov
• Status: Recruiting
• Start date: July 31, 2017
• Completion date: December 31, 2029