Natural History of Intestinal Inflammation in People With Primary Immune Dysregulations
| Status: | Recruiting |
|---|---|
| Conditions: | Irritable Bowel Syndrome (IBS), Gastrointestinal |
| Therapuetic Areas: | Gastroenterology |
| Healthy: | No |
| Age Range: | 3 - Any |
| Updated: | 4/6/2019 |
| Start Date: | April 10, 2019 |
| End Date: | April 30, 2031 |
| Contact: | Leanna M McKenzie, C.R.N.P. |
| Email: | leanna.mckenzie@nih.gov |
| Phone: | (301) 761-7601 |
Natural History of Intestinal Inflammation in Patients With Primary Immune Dysregulations
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.
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.
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.
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.
- 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
confirmed PIDD or carrier status in a current NIH protocol, regardless of an IBD
component.
- Specific Inclusion Criteria for IBD Cohort:
- 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.
We found this trial at
1
site
9000 Rockville Pike
Bethesda, Maryland 20892
Bethesda, Maryland 20892
301-496-2563
Phone: 800-411-1222
National Institutes of Health Clinical Center The National Institutes of Health (NIH) Clinical Center in...
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