Natural History of Intestinal Inflammation in People With Primary Immune Dysregulations

NCT03278912 | Withdrawn

• 2 other identifiers: 17016317-I-0163
• Study Type: observational
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

Background: PIDD stands for primary immune dysregulation. It is a general term that includes many different inherited immune system disorders. The immune system is the part of the body that helps fight disease and infection. People with PIDDs can develop many kinds of health problems. One of these is inflammatory bowel disease (IBD), which causes diarrhea and cramping. Researchers want to learn more about these disorders to develop possible treatments. Objective: To learn more about when and why IBD may develop in some people with PIDDs. Eligibility: People ages 3 and older who have PIDD or IBD. Healthy volunteers in this age group are also needed. Design: Visit 1: Participants will be screened with physical exam, medical history, and blood and urine tests. Visit 2: Participants will:

• Have more physical exams and blood and urine tests.
• Answer questions about quality of life and food history.
• Provide a stool sample.
• Have nasal and rectal skin swabs.
• Have saliva collected. Participants will have 1 follow-up visit per year. They will repeat visit 2 procedures. Participants will be contacted by phone or email in between yearly visits. They will be asked about their health. They will complete a quality-of-life questionnaire and send a stool sample that is collected at home. If participants experience a sudden change in symptoms or undergo a new treatment, they may be asked to complete visit 2 procedures. If participants are not able to come to NIH, study data and samples can be collected without an in-person visit. Participants will have a final study visit about 10 years after Visit 1. They will repeat visit 2 procedures.

Conditions

Chronic Granulomatous Disease; Inflammatory Bowel Disease

Keywords

Inflammatory Bowel Disease; Chronic Granulomatous Disease; Dysbiosis; Microbiome; Immunodeficiency; Natural History

Outcome Measures

Primary Outcomes (1)

• Disease-specific intestinal microbiome signatures, and related localized and systemic immune responses.

  1\. Microbiome, metabolomics, and transcriptomic signatures will be examined between comparison groups.

  Baseline and Annual follow-up visits spanning 10 years

Secondary Outcomes (3)

• Changes in microbiome signatures. Changes in metabolomic and transcriptomic signatures.

  Baseline and Annual follow-up visits spanning 10 years

• Changes in systemic and tissue-specific markers of innate and adaptive immunity.

  Baseline and Annual follow-up visits spanning 10 years

• Disease-specific differences in relative quantity and function of peripheral blood and tissue immune cells (includes hematopoietic and stromal cells).

  Throughout length of study

Study Arms (3)

IBD

-Patients with IBD without a diagnosed PIDD.-First- or second-degree relatives of patients with a PIDD of interest who do not have a PIDD themselves, but have diagnosed or suspected IBD.

Non-PIDD/non-IBD (healthy volunteers)

healthy volunteers

PIDD

CGD cohort; IPEX syndrome cohort; CTLA4 haploinsufficiency cohort; LRBA deficiency and hypomorphic RAG deficiency cohorts

Eligibility Criteria

• Age: 3 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

The study population will include patients and healthy volunteers greater than or equal to 3 years of age; PIDDs of interest, IBD, and Non-PIDD/non-IBD (healthy volunteers)@@@@@@

You may qualify if:

• Age greater than or equal to 3 years.
• Willing to allow storage of samples for future research.
• Willing to allow genetic testing of their samples.
• Negative urine or serum pregnancy test for women of childbearing potential.
• Enrollment as a patient with confirmed IBD in a current NIH protocol.
• Absence of clinical findings or history suggestive of a primary or acquired immunodeficiency (not including immunodeficiency caused by certain IBD treatments).
• Absence of clinical findings or history suggestive of a primary or acquired immunodeficiency.
• Absence of clinical findings or history suggestive of IBD.

You may not qualify if:

• Active malignancy requiring treatment.
• HIV.
• Current treatment for hepatitis B.
• Current treatment for hepatitis C.
• Recreational IV drug use within the past 6 months (based on subject report).
• Participation in a research study of an investigational vaccine within the past 6 months.
• Any condition that, in the opinion of the investigator, contraindicates participation in this study.
• Treatment with systemic antimicrobials within the past 3 months, unless it is a prophylactic regimen consisting of either an azole , trimethoprim-sulfamethoxazole, a quinolone, or any antimicrobial regimen resembling a typical prophylaxis regimen used to treat a PIDD of interest.
• Treatment with immune modulators within the past 6 months.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Agarwal S, Mayer L. Gastrointestinal manifestations in primary immune disorders. Inflamm Bowel Dis. 2010 Apr;16(4):703-11. doi: 10.1002/ibd.21040.

  PMID: 19637385 BACKGROUND

• Marciano BE, Rosenzweig SD, Kleiner DE, Anderson VL, Darnell DN, Anaya-O'Brien S, Hilligoss DM, Malech HL, Gallin JI, Holland SM. Gastrointestinal involvement in chronic granulomatous disease. Pediatrics. 2004 Aug;114(2):462-8. doi: 10.1542/peds.114.2.462.

  PMID: 15286231 BACKGROUND

• Uhlig HH. Monogenic diseases associated with intestinal inflammation: implications for the understanding of inflammatory bowel disease. Gut. 2013 Dec;62(12):1795-805. doi: 10.1136/gutjnl-2012-303956.

  PMID: 24203055 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Granulomatous Disease, Chronic; Inflammatory Bowel Diseases; Dysbiosis; Immunologic Deficiency Syndromes

Condition Hierarchy (Ancestors)

Phagocyte Bactericidal Dysfunction; Leukocyte Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Study Officials

• Christa S Zerbe, M.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 9, 2017
• First Posted: September 12, 2017
• Study Start: September 8, 2023
• Primary Completion: September 8, 2023
• Study Completion: September 8, 2023
• Last Updated: September 13, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: SAP
• Time Frame: Data will be shared before publication, at publication or shortly after publication.
• Access Criteria: Data will be shared through:@@@@@@ (Summation)An NIH-funded or approved public repository: National Center for Biotechnology Information Sequence Read Archive (NCBI SRA) Database.@@@@@@ (Summation)BTRIS.@@@@@@ (Summation)Approved outside collaborators under appropriate individual agreements.@@@@@@ (Summation)Publication and/or public presentations.@@@@@@The PI will review and approve/disapprove requests for IDP.

Locations

US (1)