Natural History of Intestinal Inflammation in People With Primary Immune Dysregulations

  • STATUS
    Recruiting
  • End date
    Jul 1, 2030
  • participants needed
    339
  • sponsor
    National Institute of Allergy and Infectious Diseases (NIAID)
Updated on 4 October 2022
diarrhea
urine tests
immunodeficiency
immune disorder
enteropathy

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.

Description

Over 1 million people suffer from IBD in the United States. Although the exact pathogenesis is unclear, IBD results from an inappropriate inflammatory response to intestinal microbes which is influenced by the environment in a genetically susceptible host. IBDs can be classified as conventional (Crohn disease (CD) and ulcerative colitis (UC)) and unclassified (early onset, difficult to treat, associated with monogenic disorders and PIDDs). Among the 200 IBD susceptibility loci identified in genome-wide association studies (GWAS), overlap with aberrations identified in PIDDs has been observed, thereby supporting the study of PIDDs to better understand conventional IBD pathogenesis, while recognizing PIDD-associated IBDs as distinct disease entities requiring specialized management.

The prevalence of PIDDs worldwide is estimated at 1 in 2000 live births and encompasses a growing list of over 300 PIDDs. Despite the fact that GI disease is the second most common complication in patients with PIDDs (rates ranging from 5-50%), little is known about PIDDspecific

IBD pathogenesis and even less is understood about the role of the microbiota both as a consequence and modulator of immune response in these inherited disorders. Moreover, there may be a time-limited period ("immunological window of opportunity"), coinciding with the maturation of the host s microbiome, during which early immune education may have long-term effects on predisposition to aberrant immune responses and inflammatory dysregulation. The primary objective of this study is to determine if PIDDs result in intestinal dysbioses, which alter local and systemic immune responses. Our long-term goal is to comprehensively investigate the immunological window of opportunity as it relates to PIDD-associated IBDs to define time-sensitive immunoregulatory targets for therapeutic intervention. We will pursue this goal through a prospective, longitudinal study of pediatric and adult patients with PIDDs (with and without IBD) before and after treatment and/or diagnostic interventions, including but not limited to hematopoietic stem cell transplantation (HSCT). Findings from subjects with PIDDs will be compared to those from subjects with IBD as well as healthy volunteers. This multifaceted study will complement primary patient protocols while allowing for the direct interrogation of specific arms of innate and adaptive immunity in the context of host-microbiome interactions. Patients will be studied over time through the collection of clinical metadata, blood, stool, urine, saliva, skin swabs, and biopsies obtained from clinically-indicated endoscopies in age-appropriate patients. PIDDs of interest include but are not limited to: CGD, CTLA4 and LRBA protein deficiency, hypomorphic RAG deficiency, and IPEX syndrome.

Details
Condition Chronic Granulomatous Disease, Inflammatory Bowel Disease
Clinical Study IdentifierNCT03278912
SponsorNational Institute of Allergy and Infectious Diseases (NIAID)
Last Modified on4 October 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

General Inclusion Criteria - All individuals must meet the following criteria to be eligible for study participation
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
Specific Inclusion Criteria for PIDD of Interest Cohort: Enrollment as a patient with
Specific Inclusion Criteria for IBD Cohort
confirmed PIDD or carrier status in a current NIH protocol, regardless of an
IBD component
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)
Specific Inclusion Criteria for non-PIDD/non-IBD Cohort (Healthy Volunteers)
Absence of clinical findings or history suggestive of a primary or acquired immunodeficiency
Absence of clinical findings or history suggestive of IBD

Exclusion Criteria

General Exclusion Criteria - An individual who meets any of the following criteria will be excluded from study participation
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
Specific Exclusion Criteria for PIDD of Interest Cohort: None
Specific Exclusion Criteria for IBD Cohort: None
Specific Exclusion Criteria for non-PIDD/non-IBD Cohort (Healthy Volunteers)
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
Clear my responses

How to participate?

Step 1 Connect with a study center
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer  to help accelerate the development of new treatments and to get notified about similar trials.

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Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

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If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

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Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

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