Down SyndromeNCT07416201
Natural History of Dysregulation and Aging of the Immune System in People With Trisomy 21 With and Without Thymectomy
An observational study of Down Syndrome, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
Trial summary
Background: Down syndrome is a genetic disorder that can cause heart defects and other problems in the body. People with Down syndrome are more likely to have infections, autoimmunity, and blood diseases. Some may need surgery to treat congenital heart problems. Read more about this study
- Who is it for?
- Ages 1 year to 120 yearsHealthy volunteers can take part
- Conditions the study is for
- Down Syndrome
- How many people
- 700 participants
- Where
- 1 siteUnited States
- Study dates
- 23 Jun 2026to 1 Nov 2040
- Phase
- Observational
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 year to 120 years
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Study population: Participants will be selected in an equitable manner from the available pool of potentially eligible individuals, without regard to factors such as sex, race, ethnicity, socioeconomic status, etc. To facilitate recruitment, the study will be registered in clinicaltrials.gov and will be shared with T21 advocacy groups.
Who may be able to join
- In order to be eligible to participate in this study, an individual must meet all of the following criteria:
- 1. Aged >=1 year.
- 2. Willingness to allow storage of specimens and data for future research.
- Additional Inclusion Criteria for Affected Participants
- Documented T21 based on chromosomal karyotype test.
- Ability of participant or LAR to provide informed consent.
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- Additional Inclusion Criteria for Unaffected Relatives
- Ability of participant to provide informed consent or, for individuals <18 years of age, to provide informed assent as applicable.
- Reside in the same household as the corresponding affected participant.
Who cannot join
- An individual who meets any of the following criteria will be excluded from participation in this study:
- 1. Any condition that, in the judgment of the investigator, may put the participant at undue risk or make them unsuitable for participation in the study.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
NIH Clinical Center Office of Patient Recruitment (OPR), 800-411-1222 ext. TTY dial 711, ccopr@nih.gov
Luigi Notarangelo, M.D., (301) 761-7550, luigi.notarangelo2@nih.gov
About this study
Background:
Down syndrome is a genetic disorder that can cause heart defects and other problems in the body. People with Down syndrome are more likely to have infections, autoimmunity, and blood diseases. Some may need surgery to treat congenital heart problems. During this surgery, doctors sometimes remove part of the thymus. The thymus is an organ that plays a role in immune function. People who have had part of their thymus removed may get sick more often than others do.
Read more
Objective:
This natural history study will gather data about how removing part of the thymus affects the health of people with Down syndrome.
Eligibility:
People aged 1 year and older with Down syndrome. The study will include both people who have, and those who have not had, surgery to remove part of their thymus. Healthy relatives are also needed.
Design:
Participants with Down syndrome will have clinic visits at least once a year for 15 years.
At each visit they will have a physical exam. They will give blood and stool samples. They will have tests of their heart and lung function.
Participants aged 18 years or older may have at least 1 imaging scan: They will lie on a table that slides into a donut-shaped machine. The machine uses X-rays to take pictures of the inside of the body.
Participants who have tissue samples collected from their bodies (biopsies) taken during the study may have extra tissue taken for research.
Healthy relatives will also have visits once a year for 15 years. They will only have a physical exam and provide blood and stool samples.
Read the detailed description
Study Description:
This is a longitudinal observational study of individuals with trisomy 21 (T21) to gather data on the immune function in order to identify clinical and laboratory signatures of immunodeficiency and/or immune dysregulation, characterize their pathophysiology, evaluate their progression and evolution over time, and analyze the impact of immunomodulatory and immunosuppressive treatment. In order to assess the possible impact of thymectomy on immune dysfunction and on the risk of developing autoimmunity, malignancies, and/or increased susceptibility to infections, both individuals who have had previous thymectomy and those who have not received this procedure will be included. Affected participants will have a baseline visit and follow-up study visits every year (starting from baseline) to assess their health and collect biospecimens (including but not limited to blood). Additional visits can also be scheduled as clinically indicated. Data and excess biospecimens from routine clinical care may also be collected and used for research. Unaffected relatives who live in the same household as the corresponding affected participant will be enrolled as controls and will undergo yearly blood collection and optional yearly stool, buccal swab, and saliva collections for comparison of microbiome and immunological data.
Objectives:
Primary Objectives:
- Describe the immune correlates of clinical endpoints (infections, development or progression of lung damage, autoimmunity, malignancies), and their cumulative frequency over time, in individuals with T21
- Describe the possible impact of previous thymectomy on the incidence of clinical manifestations of immune deficiency and immune dysregulation, and on laboratory parameters of immune function
Secondary Objectives:
- Identify cellular and molecular mechanisms of immune dysfunction in individuals with T21
Endpoints:
Primary Endpoints:
- Incidence of severe infections requiring hospital admission (number of admissions/year; number of days of hospitalization/year)
- Nature of infections (bacterial, viral, fungal, opportunistic pathogens) requiring hospitalization
- Number and type of autoimmune manifestations/year
- Proportion of patients with evidence of lung abnormalities at chest CT and characterization of pathological radiological findings
- Proportion of T21 individuals with malignancies by age group (compared to the general population), and type of malignancies
- Frequency of individuals with abnormal T- and B-cell counts and immunoglobulin serum levels
- Frequency of T21 individuals with laboratory evidence of autoantibodies
Secondary Endpoints:
- Distribution of subsets of T helper (Th), T follicular helper, and T regulatory (Treg) cells
- Diversity of T-cell receptor (TCR) repertoire, measured as proportion of CD4+ and CD8+ cells expressing distinct T-cell receptor Beta variable gene (TRBV) families
- Proportion of T cells exhibiting expression of exhaustion markers
- Levels of specific antibodies to immunization antigens
- Proportion of dysreactive B-cell subsets (defined as CD19(hi) CD21(low) CD38(low) B cells)
- Proportion of 9G4+ B cells and determination of their phenotype
- Levels of anti-cytokine antibodies and determination of their neutralizing activity
- Proportion of patients manifesting progression of lung damage over time as detected by chest CT and/or pulmonary function tests
Exploratory Endpoints:
- Transcriptional signatures of immune dysregulation in circulating peripheral blood mononuclear cells
- Characterization of phenotypic and transcriptional abnormalities of thymic stromal cell types generated in vitro from induced pluripotent stem cells (iPSCs) from T21 individuals compared to healthy controls
- Measurement of soluble biomarkers of inflammation
- Definition of T21 endotypes (as shown by transcriptional profile and soluble markers of inflammation), analysis of endotype persistence over time, and correlation with clinical manifestations of disease
- Metabolomic and lipidomic signatures of immune dysregulation in plasma of T21 individuals
- Perturbations of microbiome diversity and composition (as shown by comparison between relatives and proband)
- Levels of circulating VH4-34 antibodies
- Diversity and composition of T- and B-cell receptor repertoire, and molecular signatures of self-reactivity
- Identification of other genetic variants that may contribute to the immune dysregulation and infection phenotype of T21
- Conditions
- Down Syndrome
- Keywords
- Down Syndrome, Immunologic Deficiency Syndromes, THYMECTOMY
- Medical subject headings
- Down Syndrome, Immunologic Deficiency Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Trisomy 21 Participants | Participants aged >=1 year old who have T21 | |
| Unaffected Relative Participants | Participants aged >=1 year old who are related to a participant with T21 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Frequency of T21 individuals with laboratory evidence of autoantibodies
Describe the immune correlates of clinical endpoints (infections, autoimmunity, malignancies), and their cumulative frequency over time, in individuals with T21. Describe the possible impact of previous thymectomy on the incidence of clinical manifestations of immune deficiency and immune dysregulation, and on laboratory parameters of immune function
Measured: Through end of study
Number and type of autoimmune manifestations/year
Describe the immune correlates of clinical endpoints (infections, autoimmunity, malignancies), and their cumulative frequency over time, in individuals with T21. Describe the possible impact of previous thymectomy on the incidence of clinical manifestations of immune deficiency and immune dysregulation, and on laboratory parameters of immune function
Measured: Through end of study
Frequency of individuals with abnormal T and B cell counts and immunoglobulin serum levels
Describe the immune correlates of clinical endpoints (infections, autoimmunity, malignancies), and their cumulative frequency over time, in individuals with T21. Describe the possible impact of previous thymectomy on the incidence of clinical manifestations of immune deficiency and immune dysregulation, and on laboratory parameters of immune function
Measured: Through end of study
Proportion of T21 individuals with malignancies by age group (compared to the general population), and type of malignancies
Describe the immune correlates of clinical endpoints (infections, autoimmunity, malignancies), and their cumulative frequency over time, in individuals with T21. Describe the possible impact of previous thymectomy on the incidence of clinical manifestations of immune deficiency and immune dysregulation, and on laboratory parameters of immune function
Measured: Through end of study
Nature of infections (bacterial, viral, fungal, opportunistic pathogens) requiring hospitalization
Describe the immune correlates of clinical endpoints (infections, autoimmunity, malignancies), and their cumulative frequency over time, in individuals with T21. Describe the possible impact of previous thymectomy on the incidence of clinical manifestations of immune deficiency and immune dysregulation, and on laboratory parameters of immune function
Measured: Through end of study
Incidence of severe infections requiring hospital admission (number of admissions/year; number of days of hospitalization/year)
Describe the immune correlates of clinical endpoints (infections, autoimmunity, malignancies), and their cumulative frequency over time, in individuals with T21. Describe the possible impact of previous thymectomy on the incidence of clinical manifestations of immune deficiency and immune dysregulation, and on laboratory parameters of immune function
Measured: Through end of study
Secondary outcomes (5)
Levels of specific antibodies to immunization antigens
Identify cellular and molecular mechanisms of immune dysfunction in individuals with T21
Measured: Through end of study
Proportion of T cells exhibiting expression of exhaustion markers
Identify cellular and molecular mechanisms of immune dysfunction in individuals with T21
Measured: Through end of study
Diversity of T-cell receptor repertoire, measured as proportion of CD4+ and CD8+ cells expressing distinct TRBV families
Identify cellular and molecular mechanisms of immune dysfunction in individuals with T21
Measured: Through end of study
Distribution of subsets of Th, T follicular helper, and Treg cells
Identify cellular and molecular mechanisms of immune dysfunction in individuals with T21
Measured: Through end of study
Proportion of dysreactive B cell subsets (defined as CD19(hi) CD21(low) CD38(low) B cells)
Identify cellular and molecular mechanisms of immune dysfunction in individuals with T21
Measured: Through end of study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Feb 2026
- Study start23 Jun 2026
- Primary completion1 May 2040 (estimated)
- Study completion1 Nov 2040 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Down SyndromeStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 700 participants (estimated)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Luigi D Notarangelo, M.D., Principal investigator, National Institute of Allergy and Infectious Diseases (NIAID)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07416201
- Sponsor's protocol ID
- 10002372
- Other IDs
- 002372-I
- Status last verified
- 9 Oct 2026
- First submitted
- 14 Feb 2026
- Last updated
- 19 Oct 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual subjects' clinical and laboratory metadata will be de-identified. Each subject is given a unique patient code, and the metadata will be imported in ImmPort.