Immunologic Deficiency SyndromeNCT00001788
Genetic Basis of Primary Immunodeficiencies
An observational study of Immunologic Deficiency Syndrome, run by National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) at 1 site in United States.
Trial summary
The purpose of this study is to evaluate patients with primary immunodeficiency disorders to identify patients with mutations of the genes for the following proteins: Jak3, STAT1, STAT4, interleukin-7, interleukin-7 receptor, interleukin-12 receptor subunits, and others. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Immunologic Deficiency Syndrome
- How many people
- 119 participants
- Where
- 1 siteUnited States
- Study dates
- 21 Aug 2011to 16 Jul 2020
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: (1) Patients will be examined at the NIH where relevant samples will be collected for analysis.(2) Patients will be examined by outside physicians and relevant patient history and physical results and samples sent to the NIH for evaluation.(3) Patients samples may be sent to us from Duke University Medical Center, a tertiary center with extensive experience in diagnosis and treatment of primary immunodeficiencies.(4) In the future, patient samples may be sent from other tertiary care centers not identified at this time.(5) Family members of patients with primary immunodeficiencies, if they or their parents/guardians request, may be evaluated at the discretion of the investigators.
Who may be able to join
- Samples from patients with known or suspected primary immunodeficiencies, including those treated with stem cell transplants or gene correction therapy, and their families will be accepted worldwide primarily from tertiary care centers that treat patients with such immunodeficiencies.
- Such patients will have documented evidence of either opportunistic infection, recurrent infection, or unusually severe responses to infectious agents that cause mild illness in unaffected individuals. In selected cases, at the discretion of the investigators, samples for testing will be obtained from consenting adult relatives of affected individuals.
- Either patient-derived B cell lines or primary blood samples will be accepted although in some cases buccal swabs will also be accepted.
- Blood samples may be obtained from unaffected children.
- Additionally; patients with particularly interesting clinical presentations (e.g. adults with possible attenuated immunodeficiency) may be seen for outpatient visits at the NIH Clinical Center for evaluation.
- Infants with SCID or other primary immunodeficiency will not be seen; their physicians will care them for and only clinical material will be sent on such patients.
- Medically stable patients with mild to moderate immunodeficiency may be seen at the NIH.
- We will encourage the participation of women and members of minority groups in this study.
Who cannot join
- Inability to provide informed consent.
- A presence of any medical condition that would, in the opinion of the investigators, confuse the interpretation of the study.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: Molecular Basis of Primary Immunodeficiencies
The purpose of this study is to evaluate patients with primary immunodeficiency disorders to identify patients with mutations of the genes for the following proteins: Jak3, STAT1, STAT4, interleukin-7, interleukin-7 receptor, interleukin-12 receptor subunits, and others.
Patients will undergo screening history, physical examination, and clinical laboratory evaluation at referring institutions and tissue samples, or cell lines will be sent to the NIH. We will establish cell lines if necessary, prepare DNA and RNA for molecular genetic analysis and study cytokine signal transduction in patient cell lines.
Read the detailed description
The purpose of this study is to evaluate patients with primary immunodeficiency disorders to identify patients with mutations of the genes for the following proteins: Jak3, STAT1, STAT4, interleukin-7, interleukin-7 receptor, interleukin-12 receptor subunits, and others. Patients will undergo screening history, physical examination, and clinical laboratory evaluation at referring institutions and tissue samples, or cell lines will be sent to the NIH. We will establish cell lines if necessary, prepare DNA and RNA for molecular genetic analysis and study cytokine signal transduction in patient cell lines.
- Conditions
- Immunologic Deficiency Syndrome
- Keywords
- Cytokine, Stat, Jak, IL-12, Mutation, Immunodeficiency
- Medical subject headings
- 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 |
|---|---|---|
| 1 | patients with primary immunodeficiency disorders |
What is being measured
The primary outcome is the main question the study is designed to answer.
Natural History of Immunologic Deficiency Syndrome
The objectives of the study are: (1) To identify new patients with Jak3 deficiency to determine the range of mutations that occur, to study these mutations in in vitro assays and to relate these findings to the clinical presentation. We will also try to develop improved assays for the diagnosis of Jak3 deficiency. (2) To analyze the function of lymphoid and myeloid cells from patients who have undergone stem cell transplants for Jak3- and XSCID (3) To analyze patients with TB+SCID without mutations of Jak3 and c for mutations in IL- 7, IL-7 receptor genes. (4) To analyze patients with defects in cell-mediated immunity to try to identify patients with mutations of the genes encoding IL-12 subunits, IL-12 receptor subunits and the transcription factors Stat1, Stat 4 and IRF.
Measured: Enrollment with follow-up
Natural History of Immunologic Deficiency Syndrome
The objectives of the study are: (5) To analyze patients, including their tissues and cells, with defects in innate immunity, adaptive immunity, or both who clinically present with features suggestive of NEMO Syndrome or NEMO-like syndrome to identify individuals with mutations in IKK (NEMO), IB, and other genes that modify the expression and function of NFB family members.
Measured: Enrollment with follow-up
Natural History of Immunologic Deficiency Syndrome
The objectives of the study are: (6) To perform whole genome, exome, or chemical analysis of genes in selected patients and family members to discover new primary immunodeficiency related genes. Whole genome, exome, or other gene analysis will be done to determine which particular genetic variations can cause the various primary immunodeficiencies such as JAK3 deficiency or NEMO Syndrome. We also seek to study whether particular variations are associated with more or less severe illness, or with specific types of symptoms, to understand the basic mechanism by which these altered genes cause cells to function differently, and to identify other genes causing SCID or NEMO-like syndrome. In order to do this, we need blood specimens (or cells from inside the cheek) from patients and their families. We will use these samples to identify which, if any, abnormality is present in the patient s genes, and to study the behavior of immune cells in vitro.
Measured: Enrollment with follow-up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Nov 1999 (estimated)
- Study start21 Aug 2011
- Primary completion2 Jul 2019
- Study completion16 Jul 2020
Why it stopped: Investigator left NIH
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Immunologic Deficiency SyndromeStudies of the same condition, open and under way.
- 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
- Retrospective
- Enrolment
- 119 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Robert A Colbert, M.D., Principal investigator, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00001788
- Sponsor's protocol ID
- 990004
- Other IDs
- 99-AR-0004
- Status last verified
- May 2021
- First submitted
- 3 Nov 1999
- Last updated
- 27 May 2021
- Results posted
- No
Publications
Lee Y, Wessel AW, Xu J, Reinke JG, Lee E, Kim SM, Hsu AP, Zilberman-Rudenko J, Cao S, Enos C, Brooks SR, Deng Z, Lin B, de Jesus AA, Hupalo DN, Piotto DG, Terreri MT, Dimitriades VR, Dalgard CL, Holland SM, Goldbach-Mansky R, Siegel RM, Hanson EP. Genetically programmed alternative splicing of NEMO mediates an autoinflammatory disease phenotype. J Clin Invest. 2022 Mar 15;132(6):e128808. doi: 10.1172/JCI128808.
PubMed 35289316
Study at a glance
From the registry record, last updated by the sponsor on 27 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Molecular Basis of Primary Immunodeficiencies
- ClinicalTrials.gov ID
- NCT00001788
- Acronym / sponsor ID
- 990004
- Conditions
- Immunologic Deficiency Syndrome
- Keywords
- Cytokine, Stat, Jak, IL-12, Mutation, Immunodeficiency
- Study type
- Observational
- Recruitment status
- TerminatedReason stopped: Investigator left NIH
- Enrolment
- 119 participants (actual)
- Lead sponsor
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)US National Institutes of Health
- Study start
- 21 Aug 2011 (actual)
- Primary completion
- 2 Jul 2019 (actual)
- Study completion
- 16 Jul 2020 (actual)
- First posted
- 4 Nov 1999 (estimated)
- 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.
The purpose of this study is to evaluate patients with primary immunodeficiency disorders to identify patients with mutations of the genes for the following proteins: Jak3, STAT1, STAT4, interleukin-7, interleukin-7 receptor, interleukin-12 receptor subunits, and others.
Patients will undergo screening history, physical examination, and clinical laboratory evaluation at referring institutions and tissue samples, or cell lines will be sent to the NIH. We will establish cell lines if necessary, prepare DNA and RNA for molecular genetic analysis and study cytokine signal transduction in patient cell lines.
Detailed description
The purpose of this study is to evaluate patients with primary immunodeficiency disorders to identify patients with mutations of the genes for the following proteins: Jak3, STAT1, STAT4, interleukin-7, interleukin-7 receptor, interleukin-12 receptor subunits, and others. Patients will undergo screening history, physical examination, and clinical laboratory evaluation at referring institutions and tissue samples, or cell lines will be sent to the NIH. We will establish cell lines if necessary, prepare DNA and RNA for molecular genetic analysis and study cytokine signal transduction in patient cell lines.
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | – | –patients with primary immunodeficiency disorders |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- (1) Patients will be examined at the NIH where relevant samples will be collected for analysis.(2) Patients will be examined by outside physicians and relevant patient history and physical results and samples sent to the NIH for evaluation.(3) Patients samples may be sent to us from Duke University Medical Center, a tertiary center with extensive experience in diagnosis and treatment of primary immunodeficiencies.(4) In the future, patient samples may be sent from other tertiary care centers not identified at this time.(5) Family members of patients with primary immunodeficiencies, if they or their parents/guardians request, may be evaluated at the discretion of the investigators.
Key inclusion criteria (8 listed)
- Samples from patients with known or suspected primary immunodeficiencies, including those treated with stem cell transplants or gene correction therapy, and their families will be accepted worldwide primarily from tertiary care centers that treat patients with such immunodeficiencies.
- Such patients will have documented evidence of either opportunistic infection, recurrent infection, or unusually severe responses to infectious agents that cause mild illness in unaffected individuals. In selected cases, at the discretion of the investigators, samples for testing will be obtained from consenting adult relatives of affected individuals.
- Either patient-derived B cell lines or primary blood samples will be accepted although in some cases buccal swabs will also be accepted.
- Blood samples may be obtained from unaffected children.
- Additionally; patients with particularly interesting clinical presentations (e.g. adults with possible attenuated immunodeficiency) may be seen for outpatient visits at the NIH Clinical Center for evaluation.
Key exclusion criteria (2 listed)
- Inability to provide informed consent.
- A presence of any medical condition that would, in the opinion of the investigators, confuse the interpretation of the study.
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
Natural History of Immunologic Deficiency Syndrome
Time frame: Enrollment with follow-up
The objectives of the study are: (1) To identify new patients with Jak3 deficiency to determine the range of mutations that occur, to study these mutations in in vitro assays and to relate these findings to the clinical presentation. We will also try to develop improved assays for the diagnosis of Jak3 deficiency. (2) To analyze the function of lymphoid and myeloid cells from patients who have undergone stem cell transplants for Jak3- and XSCID (3) To analyze patients with TB+SCID without mutations of Jak3 and c for mutations in IL- 7, IL-7 receptor genes. (4) To analyze patients with defects in cell-mediated immunity to try to identify patients with mutations of the genes encoding IL-12 subunits, IL-12 receptor subunits and the transcription factors Stat1, Stat 4 and IRF.
Natural History of Immunologic Deficiency Syndrome
Time frame: Enrollment with follow-up
The objectives of the study are: (5) To analyze patients, including their tissues and cells, with defects in innate immunity, adaptive immunity, or both who clinically present with features suggestive of NEMO Syndrome or NEMO-like syndrome to identify individuals with mutations in IKK (NEMO), IB, and other genes that modify the expression and function of NFB family members.
Natural History of Immunologic Deficiency Syndrome
Time frame: Enrollment with follow-up
The objectives of the study are: (6) To perform whole genome, exome, or chemical analysis of genes in selected patients and family members to discover new primary immunodeficiency related genes. Whole genome, exome, or other gene analysis will be done to determine which particular genetic variations can cause the various primary immunodeficiencies such as JAK3 deficiency or NEMO Syndrome. We also seek to study whether particular variations are associated with more or less severe illness, or with specific types of symptoms, to understand the basic mechanism by which these altered genes cause cells to function differently, and to identify other genes causing SCID or NEMO-like syndrome. In order to do this, we need blood specimens (or cells from inside the cheek) from patients and their families. We will use these samples to identify which, if any, abnormality is present in the patient s genes, and to study the behavior of immune cells in vitro.
Results and safety
The study was stopped early (reason given: Investigator left NIH). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 May 2021.
- Derived from this study: PubMed 35289316Lee Y, Wessel AW, Xu J, Reinke JG, Lee E, Kim SM, Hsu AP, Zilberman-Rudenko J, Cao S, Enos C, Brooks SR, Deng Z, Lin B, de Jesus AA, Hupalo DN, Piotto DG, Terreri MT, Dimitriades VR, Dalgard CL, Holland SM, Goldbach-Mansky R, Siegel RM, Hanson EP. Genetically programmed alternative splicing of NEMO mediates an autoinflammatory disease phenotype. J Clin Invest. 2022 Mar 15;132(6):e128808. doi: 10.1172/JCI128808.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
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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.
Robert A Colbert, M.D. principal investigator
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
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 Immunologic Deficiency Syndrome, run by National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) 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 8 inclusion and 2 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: stopped early, as of the sponsor's last update on 27 May 2021. 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 stopped early (reason given: Investigator left NIH). Results are not available in the source record.
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?
Natural History of Immunologic Deficiency Syndrome (time frame: Enrollment with follow-up). The study lists 3 primary outcomes in all. 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 NCT00001788, which also lists 1 linked publication.
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 27 May 2021.