Natural History of Trisomy 8-Associated Autoinflammatory Disease (TRIAD) and Related Disorders

July 2, 2026 updated by: National Institute of Allergy and Infectious Diseases (NIAID)

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.

Study Overview

Status

Recruiting

Conditions

Detailed 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.

Study Type

Observational

Enrollment (Estimated)

750

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • Maryland
      • Bethesda, Maryland, United States, 20892
        • Recruiting
        • National Institutes of Health Clinical Center
        • Contact:
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Outside provider referral, current NIH study patients

Description

  • 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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
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 is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
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
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.
Length of the study

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Length of study
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.
Length of study
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.
Length of study
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.
Length of study

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

  • Principal Investigator: Kalpana Manthiram, M.D., National Institute of Allergy and Infectious Diseases (NIAID)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

July 8, 2026

Primary Completion (Estimated)

May 1, 2056

Study Completion (Estimated)

June 1, 2056

Study Registration Dates

First Submitted

July 2, 2026

First Submitted That Met QC Criteria

July 2, 2026

First Posted (Actual)

July 6, 2026

Study Record Updates

Last Update Posted (Actual)

July 6, 2026

Last Update Submitted That Met QC Criteria

July 2, 2026

Last Verified

July 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 10002326
  • 002326-I

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

This study will comply with the NIH Data Management and Sharing (DMS) Policy, which applies to all new and ongoing NIH-funded research in the IRP, as of January 25, 2023, that is associated with a ZIA, with a clinical protocol that undergoes scientific review and/or will involve genomic data sharing. @@@@@@This study will comply with the NIH Genomic Data Sharing (GDS) Policy, which applies to all new and ongoing NIH IRP-funded research, as of August 31, 2015, that generates large-scale human or non-human genomic data, as well as the use of these data for subsequent research. Large-scale data include GWAS, SNP arrays, and genome sequence, transcriptomic, epigenomic, and gene expression data.@@@@@@

IPD Sharing Time Frame

Upon publication

IPD Sharing Access Criteria

Requests will be assessed by the PI. Next generation sequencing data will be deposited into public repositories.

IPD Sharing Supporting Information Type

  • SAP
  • ANALYTIC_CODE
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Trisomy 8 Mosaicism

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Rwanda

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe