Chronic Granulomatous DiseaseNCT03278912
Natural History of Intestinal Inflammation in People With Primary Immune Dysregulations
An observational study of Chronic Granulomatous Disease and Inflammatory Bowel Disease, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 3 years and olderHealthy volunteers can take part
- Conditions the study is for
- Chronic Granulomatous Disease, Inflammatory Bowel Disease
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 8 Sep 2023to 8 Sep 2023
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 3 years and older
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
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)@@@@@@
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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).
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- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
Official title: 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.
Read more
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.
Read the detailed 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.
- Keywords
- Inflammatory Bowel Disease, Chronic Granulomatous Disease, Dysbiosis, Microbiome, Immunodeficiency, Natural History
- Medical subject headings
- Granulomatous Disease, Chronic, Inflammatory Bowel Diseases, Dysbiosis, Immunologic Deficiency Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Disease-specific intestinal microbiome signatures, and related localized and systemic immune responses.
- Microbiome, metabolomics, and transcriptomic signatures will be examined between comparison groups.
Measured: Baseline and Annual follow-up visits spanning 10 years
Secondary outcomes (3)
Changes in microbiome signatures. Changes in metabolomic and transcriptomic signatures.
- Microbiome, metabolomics, and transcriptomic signatures will be examined between comparison groups.
Measured: Baseline and Annual follow-up visits spanning 10 years
Changes in systemic and tissue-specific markers of innate and adaptive immunity.
- For evaluation of markers of innate and adaptive immunity (local and systemic) most comparisons will be made using 2-tailed Student t tests with statistical significance set at a p less than or equal to 0.05.
Measured: 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).
- For evaluation of disease-specific differences in relative quantity and function of peripheral blood and tissue immune cells most comparisons will be made using 2-tailed Student t tests with statistical significance set at a p less than or equal to 0.05.
Measured: Throughout length of study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Sep 2017
- Study start8 Sep 2023
- Primary completion8 Sep 2023
- Study completion8 Sep 2023
Why it stopped: Funding completed.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Chronic Granulomatous DiseaseStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Christa S Zerbe, M.D., Principal investigator, National Institute of Allergy and Infectious Diseases (NIAID)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03278912
- Sponsor's protocol ID
- 170163
- Other IDs
- 17-I-0163
- Status last verified
- Sep 2023
- First submitted
- 9 Sep 2017
- Last updated
- 13 Sep 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: .The following will be shared:@@@@@@ (Summation)De-identified data in an NIH-funded or approved public repository.@@@@@@ (Summation)Identified data in the Biomedical Translational Research Information System (BTRIS).@@@@@@.De-identified or identified data with approved NIH-based and/or outside collaborators under appropriate agreements.
Publications
Agarwal S, Mayer L. Gastrointestinal manifestations in primary immune disorders. Inflamm Bowel Dis. 2010 Apr;16(4):703-11. doi: 10.1002/ibd.21040.
PubMed 19637385Marciano 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.
PubMed 15286231Uhlig 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.
PubMed 24203055
Study at a glance
From the registry record, last updated by the sponsor on 13 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Natural History of Intestinal Inflammation in Patients With Primary Immune Dysregulations
- ClinicalTrials.gov ID
- NCT03278912
- Acronym / sponsor ID
- 170163
- Keywords
- Inflammatory Bowel Disease, Chronic Granulomatous Disease, Dysbiosis, Microbiome, Immunodeficiency, Natural History
- Study type
- Observational
- Recruitment status
- WithdrawnReason stopped: Funding completed.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- 8 Sep 2023 (actual)
- Primary completion
- 8 Sep 2023 (actual)
- Study completion
- 8 Sep 2023 (actual)
- First posted
- 12 Sep 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 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 |
Who may qualify
- Ages
- 3 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
- 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)@@@@@@
Key inclusion criteria (12 listed)
- General Inclusion Criteria - All individuals must meet the following criteria to be eligible for study participation:
- 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:
- Specific Inclusion Criteria for non-PIDD/non-IBD Cohort (Healthy Volunteers):
Key exclusion criteria (13 listed)
- General Exclusion Criteria - An individual who meets any of the following criteria will be excluded from study participation:
- 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):
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Disease-specific intestinal microbiome signatures, and related localized and systemic immune responses.
Time frame: Baseline and Annual follow-up visits spanning 10 years
1. Microbiome, metabolomics, and transcriptomic signatures will be examined between comparison groups.
3 secondary outcomes
Changes in microbiome signatures. Changes in metabolomic and transcriptomic signatures.
Time frame: Baseline and Annual follow-up visits spanning 10 years
Changes in systemic and tissue-specific markers of innate and adaptive immunity.
Time frame: 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).
Time frame: Throughout length of study
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Sep 2023.
- Background: PubMed 19637385Agarwal S, Mayer L. Gastrointestinal manifestations in primary immune disorders. Inflamm Bowel Dis. 2010 Apr;16(4):703-11. doi: 10.1002/ibd.21040.
- Background: PubMed 15286231Marciano 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.
- Background: PubMed 24203055Uhlig 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.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. .The following will be shared:@@@@@@ (Summation)De-identified data in an NIH-funded or approved public repository.@@@@@@ (Summation)Identified data in the Biomedical Translational Research Information System (BTRIS).@@@@@@.De-identified or identified data with approved NIH-based and/or outside collaborators under appropriate agreements.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Christa S Zerbe, M.D. principal investigator
National Institute of Allergy and Infectious Diseases (NIAID)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Chronic Granulomatous Disease and Inflammatory Bowel Disease, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 13 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Disease-specific intestinal microbiome signatures, and related localized and systemic immune responses. (time frame: Baseline and Annual follow-up visits spanning 10 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03278912, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Sep 2023.