Clinical trial NCT06944067: Study to Understand the Genetic Risk of Developing an Immune Response After Blood Transfusions Among Individuals With Sickle Cell Disease
Official title: Observational Study to Determine Red Blood Cell Alloimmunization Risk Etiology in Patients With Sickle Cell Disease
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Sickle Cell Disease
Keywords: Sickle Cell Disease
Transfusion
Alloimmunization
Lead sponsor: National Institutes of Health Clinical Center (CC)
Sponsor class: NIH
First posted: 2025-04-25
Enrollment: 50
Sex: ALL
Minimum age (years): 2
Maximum age (years): 99
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Individuals with sickle cell disease who may or may not have had a history of alloimmune response to blood transfusions. The study population will include children ages 2-17 years old and adults. The study population will not include pregnant women, people taking immunosuppressive medications, or people with a history of transplant (e.g., bone marrow or stem cell transplant).

Brief summary: The purpose of this research study is to look at genes and determine how they interact with each other to find changes that could explain why some people's immune systems may respond to blood transfusions. This response is called an alloimmune response. We strongly believe that when someone has an alloimmune response, it is caused by changes in their genes. We plan to compare changes in the genes of individuals that develop red blood cell alloimmunization after blood transfusions with those that do not develop alloimmunization. This may help us to create more targeted therapeutic interventions, which may improve the health of alloimmune responders.

Detailed description: Study Description:

This study seeks to fine-map risk variants associated with increased susceptibility to developing red blood cell alloantibodies in patients with sickle cell disease (SCD), with the goal of characterizing the molecular basis of the alloimmunization response. This will allow for improved clinical management for individuals susceptible to alloimmunization responses.

Objectives:

Primary Objective:

Elucidate the role of previously identified risk loci in the development of alloantibodies among individuals with SCD.

Secondary Objective:

Validate and characterize additional, novel alloimmunization-related candidate loci.

Endpoints:

Primary Endpoint:

Completion of analysis of previously identified risk loci to determine the relationship between genome structure and expression.

Secondary Endpoint:

No additional candidate loci from concurrent discovery studies to evaluate.

Eligibility criteria: * INCLUSION CRITERIA

To be eligible to participate in this study, an individual must meet all of the following criteria:

1. Individual (\> 2 years of age) with confirmed SCD diagnosis who meets at least one of the following conditions:

1. History of greater than ten administered transfusions or 20 transfusion units (where known)
2. History of one or more antibody screens
3. Known candidate variant genotype

EXCLUSION CRITERIA

An individual who meets any the following criteria will be excluded from participation in this study:

1. Impaired decision-making capability, with or without a legally authorized representative
2. History of transplant (e.g., organ, bone marrow, stem cell)
3. Taking immunosuppressive medications at time of enrollment
4. Confirmed pregnancy

Primary outcomes:
measure: Completion of analysis of previously identified risk loci to determine the relationship between genome structure and expression.
timeFrame: 5 years
Secondary outcomes:
measure: No additional candidate loci from concurrent discovery studies to evaluate.
timeFrame: 5 years
Other outcomes:
Locations:
city: Bethesda
country: United States
facility: National Institutes of Health Clinical Center
state: Maryland
Study officials:
affiliation: National Human Genome Research Institute (NHGRI)
name: Neil A Hanchard, M.D.
role: PRINCIPAL_INVESTIGATOR
References: