Natural History of Trisomy 8-Associated Autoinflammatory Disease (TRIAD) and Related Disorders
Trisomy 8 Mosaicism · Trisomy 8 Associated Autoinflammatory Disease · Mucosal Ulcerations
What this study involves
The registry says this study is recruiting. Individual locations may have different availability.
- Study type
- Observational
- Phase
- Not applicable / not listed
- Age range
- 1 days - 99 years
- Sex eligible
- All sexes
- Healthy volunteers
- Not accepted
- Participants
- 750 Estimated
These are starting points, not an eligibility decision. The research team must review the full requirements.
About the research
Background:
Trisomy 8 mosaicism is a genetic disorder that can increase inflammation in the body. Symptoms include fevers; sores or ulcers in the mouth, digestive tract, or genital area; skin rashes; problems in organs or tissues; and changes in bone marrow cells. Researchers want to conduct a natural history study to learn more about these symptoms and what causes them.
Objective:
To gather data and samples from people with and without the trisomy 8 mosaicism.
Eligibility:
People of any age with the trisomy 8 gene mosaicism. Their healthy relatives are also needed.
Design:
Affected participants will have visits every 1 to 2 years for 30 years at NIH. Each visit will take 1 to 5 days and may be in-person or remote. With remote visits, participants may have a video call with the study team and samples may be sent to researchers by mail.
Participants may have these procedures:
Physical exam, with blood tests.
Tests of brain function and motor skills.
Sensory tests. Researchers will see how participants respond to sensations such as pinpricks, heat, cold, and pressure.
Magnetic resonance imaging (MRI) scan of the brain and/or spine.
X-ray of the spine.
Ultrasound test of heart function (echocardiogram).
Tissues samples (biopsies) collected from the skin, inside of the mouth, and bone marrow.
Swabs to collect cells from the mouth, skin, and vagina.
Collection of blood, stool, urine, saliva, hair, and fingernail samples.
X-rays, MRI, and heart tests will be done only once. Other procedures may be repeated at each visit. All tests and procedures are voluntary.
Healthy relatives who enroll will have a baseline visit and then follow-up visits as needed. They will have a physical exam. The inside of their mouth may be swabbed. Samples of blood, stool, urine, and saliva may be taken.
Read the full description
Study Description:
This is a natural history protocol designed to characterize the clinical spectrum of trisomy 8 mosaicism and trisomy 8-associated autoinflammatory disease (TRIAD) and related autoinflammatory disorders and further evaluate approaches to screening, diagnosis, and management. We will enroll affected patients and their unaffected relatives and collect a variety of clinical data and biological specimens for research analyses to better understand disease mechanisms. Biological samples from affected participants may include biopsies from the oral mucosa, skin, and bone marrow; swabs of the mouth, skin, and vagina; urine, stool, and saliva collections; and hair and fingernail clippings. Other clinical data may include imaging studies (such as magnetic resonance imaging \[MRI\], x-rays, and echocardiogram), questionnaires, and results from medical consults and clinically indicated procedures. Biological samples from unaffected relatives of participants may include blood, mouth swabs, stool, urine, and saliva. Participants may be seen in person or remotely via telehealth and provide send-in samples. After the initial baseline assessment, optional follow-up visits will occur approximately every 1 to 2 years, depending on the scientific needs of the study team and the participant s clinical status and interest.
Objectives:
Primary Objectives:
1. Characterize the clinical spectrum and natural history of trisomy 8 mosaicism and related disorders.
2. Characterize the immunologic profile in blood, tissue, and bone marrow of participants with trisomy 8 mosaicism and related disorders.
Secondary Objectives:
1. Determine appropriate screening and diagnostic workup of individuals with trisomy 8 mosaicism and related disorders.
2. Identify the long-term risk of and association with neoplasm among individuals with trisomy 8 mosaicism.
3. Characterize the distribution of trisomy 8 cells in different tissues and cell types and describe how this contributes to disease manifestations and variability.
4. Evaluate or characterize immune responses to targeted therapeutics to better understand the pathophysiology of trisomy 8 mosaicism and related disorders.
Exploratory Objectives:
1. Identify the specific genes and immunologic pathways that lead to disease manifestations seen in patients with trisomy 8.
2. Identify new genetic diseases that lead to mucosal ulcers and understand the immunologic mechanisms that contribute to mucosal ulcerations.
Endpoints:
Primary Endpoints:
1. Clinical characterization of participants with trisomy 8 mosaicism and related disorders based on history, physical examination, radiologic imaging, and laboratory testing.
2. Characterization of immunologic profile of participants with trisomy 8 mosaicism and related disorders over time in comparison to healthy controls using cellular and molecular techniques including, but not limited to immune cell phenotyping, transcriptomics, proteomics, and ex vivo functional studies.
Secondary Endpoints:
1. Characterization of laboratory, radiologic, biopsy, and physical exam findings.
2. Identification of individuals with trisomy 8 who develop malignancy and assessment of risk factors including but not limited to history, findings on bone marrow biopsies and complete blood counts (CBCs), next-generation sequencing (NGS) for risk variants, and flow cytometry.
3. Determination of the percentage of trisomy 8 cells in various tissue types including bone marrow, blood, fibroblasts cultured from skin, and biopsy samples, and the association with clinical phenotype.
4. Assessment of immune response to therapeutics based on inflammatory markers, clinical history, and physical exam findings.
Exploratory Endpoint:
1\. Identification of genes that may lead to mucosal ulcerative disease when mutated or over/underexpressed.
Who may be able to participate?
The list below is the sponsor’s full registry wording. It can include conditions, prior treatment, test results and other requirements. A match in search does not mean you qualify.
- INCLUSION CRITERIA:
To be eligible to participate in this study, an individual must meet the following criteria:
1. Stated willingness to comply with study requirements.
2. Aged \<= 99 (ability to be seen at NIH vs. remote visit may be determined by age and location).
3. Willingness to allow storage of data and specimens for future research.
Additional Inclusion Criteria for Affected Participants
1. Must have one of the following:
1. Trisomy 8 mosaicism verified by genetic testing (including but not limited to karyotype, fluorescence in situ hybridization \[FISH\], whole genome sequencing \[WGS\], whole exome sequencing \[WES\], or microarray), or
2. Inflammatory mucosal ulcerative disease clinically similar to TRIAD at the discretion of the principal investigator.
2. Ability of participant or LAR to provide informed consent.
Additional Inclusion Criteria for Biological Relatives
1. Be an unaffected biological relative of an affected participant.
2. Ability to provide informed consent.
3. Willingness to provide at least one biospecimen.
EXCLUSION CRITERIA:
Individuals with any condition or who are taking any medications that, in the opinion of the investigator, contraindicates participation in the study will be excluded.
Co-enrollment guidelines: Enrollment in this protocol does not preclude individuals from enrolling or participating in any other NIH protocols, including studies of investigational agents. Participants will be asked about their participation in other studies to ensure that blood draws do not exceed NIH limits for research protocols.
Study population
Outside provider referral, current NIH study patients
Understand screeningTreatment, groups and participation
The registry may describe treatments and study duration without a complete visit calendar. Ask the study team for the exact schedule, procedures, risks, costs and alternatives. Keep your usual care plan unless your treating clinician tells you otherwise.
- Assignment
- Not reported
- Masking
- Not reported
Affected Participants
Individuals ages \<= 99 with known or suspected trisomy 8 mosaicism, or with clinical phenotype consisting of mucosal ulcerations similar to TRIAD.
Non-affected biological family member participants
Non-affected biological family members of enrolled participants.
What researchers are measuring
Outcome measures describe what is being studied. They are not proof that a treatment works.
Primary measures
Clinical characterization of participants with trisomy 8 mosaicism and related disorders based on history, physical examination, radiologic imaging, and laboratory testing.
Time frame: Length of the study
Characterize the clinical spectrum and natural history of trisomy 8 mosaicism and related disorders.
Characterization of immunologic profile of participants with trisomy 8 mosaicism and related disorders over time in comparison to healthy controls using cellular and molecular techniques
Time frame: Length of the study
Characterization of immunologic profile of participants with trisomy 8 mosaicism and related disorders over time in comparison to healthy controls using cellular and molecular techniques including, but not limited to immune cell phenotyping, transcriptomics, proteomics, and ex vivo functional studies.
Secondary measures
Characterization of laboratory, radiologic examinations, biopsies, and physical exam findings.
Time frame: Length of study
Determine appropriate screening and diagnostic workup of individuals with trisomy 8 mosaicism and related disorders.
Identification of individuals with trisomy 8 who develop malignancy and assessment of risk factors including but not limited to history, findings on bone marrow biopsies and CBCs, NGS for risk variants, and flow cytometry.
Time frame: Length of study
Identify the long-term risk of and association with neoplasm among individuals with trisomy 8 mosaicism.
Determination of the percentage of trisomy 8 cells in various tissue types including bone marrow, blood, fibroblasts cultured from skin, and biopsy samples, and the association with clinical phenotype.
Time frame: Length of study
Characterize the distribution of trisomy 8 cells in different tissues and cell types and describe how this contributes to disease manifestations and variability.
Assessment of treatment response based on inflammatory markers, clinical history, and physical exam findings.
Time frame: Length of study
Identify effective treatments for inflammatory symptoms among those with trisomy 8 mosaicism and related disorders.
Review the complete result tables and limitations in the official record.
Open official results ↗Research locations (1)
The overall study status and a local site’s status can differ. Confirm that location’s availability before traveling.
1 locations
National Institutes of Health Clinical CenterBethesda, Maryland, United StatesRecruiting
Study team and timeline
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)
- Study start
- Nov 15, 2026 Estimated
- Primary completion
- May 1, 2056 Estimated
- Study completion
- Jun 1, 2056 Estimated
- First posted
- Jul 6, 2026 Actual
- Last updated
- Nov 10, 2026 Actual
Official study contacts
Official study title
Natural History of Trisomy 8-Associated Autoinflammatory Disease (TRIAD) and Related Disorders
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Source: ClinicalTrials.gov API v2. Information is submitted by sponsors and investigators. NLM does not approve the safety or science of all listed studies. Registry disclaimer.
Retrieved: Nov 12, 2026 · Last registry update: Nov 10, 2026