Immune DeficiencyNCT03707782
Mechanisms of Immune Deficiency
An observational study of Immune Deficiency, run by University of Colorado, Denver at 1 site in United States.
Trial summary
1. The purpose of this study is to learn more about the changes in genes, cells and proteins that cause immune deficiency diseases. 2. The early stages of the study will focus on two groups of patients: 1. members of families in which several persons have symptoms or medical histories that suggest immune deficiency. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Immune Deficiency
- How many people
- 200 participants
- Where
- 1 siteUnited States
- Study dates
- 20 Oct 2020to Dec 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 18 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Individuals aged 18 years or older and have an immune deficiency or are related to a person who has an immune deficiency.
Who may be able to join
- Immunodeficiency disease; or
- family member of individual with immunodeficiency disease
Who cannot join
- Persons with immune deficiencies that are secondary to other diseases such as malignancies.
- Persons who do not have immune deficiencies, persons who are not meet eligibility criteria
Trial locations and contacts
1 site in 1 country.
United States1 site, 1 recruiting
- Recruiting
UColorado
Denver, Colorado, 80045
Charles H Kirkpatrick, MD, 303-724-7197, charles.kirkparick@ucdenver.edu
About this study
- The purpose of this study is to learn more about the changes in genes, cells and proteins that cause immune deficiency diseases.
- The early stages of the study will focus on two groups of patients:
- members of families in which several persons have symptoms or medical histories that suggest immune deficiency.
- Patients who have received treatments with medications or drugs that affect functions of the immune system (secondary immune deficiencies).
It is hoped that studies will provide guidelines for extension of the research to other patient groups. Up to 200 patients and family members will be invited to participate.
Read the detailed description
The experiments that are proposed in this portion of the study are intended to:
- characterize the significance of the variant form of EZH2 identified in this family. They will characterize the degree of methylation of lysine 27 of histone H3 in subjects with the variant and members of the same family who have the wild type gene. The functional methyltransferase activity of the variant and wild type genes will be measured.
- characterize the current status of B-cell maturation and function in subjects with either the variant gene and the wild type gene.
- characterize B-cell function (antibody production) and the quality of antibody produced after immunizations in subjects with the wild type gene or the variant gene.
- Conditions
- Immune Deficiency
- 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 |
|---|---|---|
| Individuals with immune deficiencies | aged 18 years or older and have an immune deficiency | |
| Family members | aged 18 years or older and are related to a person who has an immune deficiency |
What is being measured
The primary outcome is the main question the study is designed to answer.
Measurement of Serum immune globulin
The clinical definition of "hypogamma-globulinemia is values that are 2 SD below the mean value for the testing laboratory. For this study values that are below the lower limit of abnormal will be scored as abnormal. Chi-square analysis or Fisher's exact test will compare values between subjects with the wild type gene and the variant gene.
Measured: each year for up to 20 years
Antibody responses
A four-fold difference or a post-immunization titer of ≥1.3 µg/ml is scored as a true antibody response. Antibody titers and avidity indices are transformed to log2 and evaluated using the Student's T-test.
Measured: 4 weeks
Measurement of NK cell function
Spearman correlation will be used to compare the relationship between expression of CD207a by NK cells that are activated with K562 cells or NK cells that are activated with PMA/iono.
Measured: one time
DNA sequencing
When indicated, whole exome or whole genome sequencing will be done to identify genetic basis (if any) of the immune deficiency
Measured: one time
measurement of cellular components of the immune system
Flow cytometry will be used to identify numbers of cells of various types (e.g.,subpopulations of B-cells and T-cells) to evaluate changes in various cell populations over time. This is especially important for studies of family members who carry disease-causing or disease-associated genes but are clinically health at the time of the first study
Measured: each year for up to 20 years
health outcome measurements
The SF-36 form will be used serially to identify changes in health over time
Measured: each year for up to 20 years
Measurement of avidity
avidity indices are transformed to log2 and evaluated using the Student's T-test
Measured: each year for up to 20 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Oct 2018
- Study start20 Oct 2020
- Primary completionDec 2023 (estimated)
- Study completionDec 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Immune DeficiencyStudies of the same condition, open and under way.
- More trials run by University of Colorado, DenverThe 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
- Family based
- Time perspective
- Prospective
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Colorado, Denver
- Sponsor type
- University, hospital or other
- Collaborators
- Colorado Clinical & Translational Sciences Institute
- Responsible party
- Sponsor
- Investigators
- Charles Kirkpatrick, Principal investigator, University of Colorado, Denver
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03707782
- Sponsor's protocol ID
- 18-0337
- Status last verified
- Apr 2022
- First submitted
- 12 Oct 2018
- Last updated
- 19 Apr 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Bonilla FA, Khan DA, Ballas ZK, Chinen J, Frank MM, Hsu JT, Keller M, Kobrynski LJ, Komarow HD, Mazer B, Nelson RP Jr, Orange JS, Routes JM, Shearer WT, Sorensen RU, Verbsky JW, Bernstein DI, Blessing-Moore J, Lang D, Nicklas RA, Oppenheimer J, Portnoy JM, Randolph CR, Schuller D, Spector SL, Tilles S, Wallace D; Joint Task Force on Practice Parameters, representing the American Academy of Allergy, Asthma & Immunology; the American College of Allergy, Asthma & Immunology; and the Joint Council of Allergy, Asthma & Immunology. Practice parameter for the diagnosis and management of primary immunodeficiency. J Allergy Clin Immunol. 2015 Nov;136(5):1186-205.e1-78. doi: 10.1016/j.jaci.2015.04.049. Epub 2015 Sep 12.
PubMed 26371839O'Meara MM, Simon JA. Inner workings and regulatory inputs that control Polycomb repressive complex 2. Chromosoma. 2012 Jun;121(3):221-34. doi: 10.1007/s00412-012-0361-1. Epub 2012 Feb 19.
PubMed 22349693Su IH, Basavaraj A, Krutchinsky AN, Hobert O, Ullrich A, Chait BT, Tarakhovsky A. Ezh2 controls B cell development through histone H3 methylation and Igh rearrangement. Nat Immunol. 2003 Feb;4(2):124-31. doi: 10.1038/ni876. Epub 2002 Dec 23.
PubMed 12496962Caganova M, Carrisi C, Varano G, Mainoldi F, Zanardi F, Germain PL, George L, Alberghini F, Ferrarini L, Talukder AK, Ponzoni M, Testa G, Nojima T, Doglioni C, Kitamura D, Toellner KM, Su IH, Casola S. Germinal center dysregulation by histone methyltransferase EZH2 promotes lymphomagenesis. J Clin Invest. 2013 Dec;123(12):5009-22. doi: 10.1172/JCI70626. Epub 2013 Nov 8.
PubMed 24200695Bodor C, Grossmann V, Popov N, Okosun J, O'Riain C, Tan K, Marzec J, Araf S, Wang J, Lee AM, Clear A, Montoto S, Matthews J, Iqbal S, Rajnai H, Rosenwald A, Ott G, Campo E, Rimsza LM, Smeland EB, Chan WC, Braziel RM, Staudt LM, Wright G, Lister TA, Elemento O, Hills R, Gribben JG, Chelala C, Matolcsy A, Kohlmann A, Haferlach T, Gascoyne RD, Fitzgibbon J. EZH2 mutations are frequent and represent an early event in follicular lymphoma. Blood. 2013 Oct 31;122(18):3165-8. doi: 10.1182/blood-2013-04-496893. Epub 2013 Sep 19.
PubMed 24052547
Study at a glance
From the registry record, last updated by the sponsor on 19 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mechanisms of Immune Deficiency
- ClinicalTrials.gov ID
- NCT03707782
- Acronym / sponsor ID
- 18-0337
- Conditions
- Immune Deficiency
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- University of Colorado, DenverUniversity, hospital or other
- Collaborators
- Colorado Clinical & Translational Sciences Institute
- Study start
- 20 Oct 2020 (actual)
- Primary completion
- Dec 2023 (estimated)
- Study completion
- Dec 2023 (estimated)
- First posted
- 16 Oct 2018 (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.
- The purpose of this study is to learn more about the changes in genes, cells and proteins that cause immune deficiency diseases.
- The early stages of the study will focus on two groups of patients:
- members of families in which several persons have symptoms or medical histories that suggest immune deficiency.
- Patients who have received treatments with medications or drugs that affect functions of the immune system (secondary immune deficiencies).
It is hoped that studies will provide guidelines for extension of the research to other patient groups. Up to 200 patients and family members will be invited to participate.
Detailed description
The experiments that are proposed in this portion of the study are intended to:
- characterize the significance of the variant form of EZH2 identified in this family. They will characterize the degree of methylation of lysine 27 of histone H3 in subjects with the variant and members of the same family who have the wild type gene. The functional methyltransferase activity of the variant and wild type genes will be measured.
- characterize the current status of B-cell maturation and function in subjects with either the variant gene and the wild type gene.
- characterize B-cell function (antibody production) and the quality of antibody produced after immunizations in subjects with the wild type gene or the variant gene.
Study design
- Observational model
- Family based
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Individuals with immune deficiencies | – | –aged 18 years or older and have an immune deficiency |
| Family members | – | –aged 18 years or older and are related to a person who has an immune deficiency |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Individuals aged 18 years or older and have an immune deficiency or are related to a person who has an immune deficiency.
Key inclusion criteria (2 listed)
- Immunodeficiency disease; or
- family member of individual with immunodeficiency disease
Key exclusion criteria (2 listed)
- Persons with immune deficiencies that are secondary to other diseases such as malignancies.
- Persons who do not have immune deficiencies, persons who are not meet eligibility criteria
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
Measurement of Serum immune globulin
Time frame: each year for up to 20 years
The clinical definition of "hypogamma-globulinemia is values that are 2 SD below the mean value for the testing laboratory. For this study values that are below the lower limit of abnormal will be scored as abnormal. Chi-square analysis or Fisher's exact test will compare values between subjects with the wild type gene and the variant gene.
Antibody responses
Time frame: 4 weeks
A four-fold difference or a post-immunization titer of ≥1.3 µg/ml is scored as a true antibody response. Antibody titers and avidity indices are transformed to log2 and evaluated using the Student's T-test.
Measurement of NK cell function
Time frame: one time
Spearman correlation will be used to compare the relationship between expression of CD207a by NK cells that are activated with K562 cells or NK cells that are activated with PMA/iono.
DNA sequencing
Time frame: one time
When indicated, whole exome or whole genome sequencing will be done to identify genetic basis (if any) of the immune deficiency
measurement of cellular components of the immune system
Time frame: each year for up to 20 years
Flow cytometry will be used to identify numbers of cells of various types (e.g.,subpopulations of B-cells and T-cells) to evaluate changes in various cell populations over time. This is especially important for studies of family members who carry disease-causing or disease-associated genes but are clinically health at the time of the first study
health outcome measurements
Time frame: each year for up to 20 years
The SF-36 form will be used serially to identify changes in health over time
Measurement of avidity
Time frame: each year for up to 20 years
avidity indices are transformed to log2 and evaluated using the Student's T-test
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Apr 2022.
- Background: PubMed 26371839Bonilla FA, Khan DA, Ballas ZK, Chinen J, Frank MM, Hsu JT, Keller M, Kobrynski LJ, Komarow HD, Mazer B, Nelson RP Jr, Orange JS, Routes JM, Shearer WT, Sorensen RU, Verbsky JW, Bernstein DI, Blessing-Moore J, Lang D, Nicklas RA, Oppenheimer J, Portnoy JM, Randolph CR, Schuller D, Spector SL, Tilles S, Wallace D; Joint Task Force on Practice Parameters, representing the American Academy of Allergy, Asthma & Immunology; the American College of Allergy, Asthma & Immunology; and the Joint Council of Allergy, Asthma & Immunology. Practice parameter for the diagnosis and management of primary immunodeficiency. J Allergy Clin Immunol. 2015 Nov;136(5):1186-205.e1-78. doi: 10.1016/j.jaci.2015.04.049. Epub 2015 Sep 12.
- Background: PubMed 22349693O'Meara MM, Simon JA. Inner workings and regulatory inputs that control Polycomb repressive complex 2. Chromosoma. 2012 Jun;121(3):221-34. doi: 10.1007/s00412-012-0361-1. Epub 2012 Feb 19.
- Background: PubMed 12496962Su IH, Basavaraj A, Krutchinsky AN, Hobert O, Ullrich A, Chait BT, Tarakhovsky A. Ezh2 controls B cell development through histone H3 methylation and Igh rearrangement. Nat Immunol. 2003 Feb;4(2):124-31. doi: 10.1038/ni876. Epub 2002 Dec 23.
- Background: PubMed 24200695Caganova M, Carrisi C, Varano G, Mainoldi F, Zanardi F, Germain PL, George L, Alberghini F, Ferrarini L, Talukder AK, Ponzoni M, Testa G, Nojima T, Doglioni C, Kitamura D, Toellner KM, Su IH, Casola S. Germinal center dysregulation by histone methyltransferase EZH2 promotes lymphomagenesis. J Clin Invest. 2013 Dec;123(12):5009-22. doi: 10.1172/JCI70626. Epub 2013 Nov 8.
- Background: PubMed 24052547Bodor C, Grossmann V, Popov N, Okosun J, O'Riain C, Tan K, Marzec J, Araf S, Wang J, Lee AM, Clear A, Montoto S, Matthews J, Iqbal S, Rajnai H, Rosenwald A, Ott G, Campo E, Rimsza LM, Smeland EB, Chan WC, Braziel RM, Staudt LM, Wright G, Lister TA, Elemento O, Hills R, Gribben JG, Chelala C, Matolcsy A, Kohlmann A, Haferlach T, Gascoyne RD, Fitzgibbon J. EZH2 mutations are frequent and represent an early event in follicular lymphoma. Blood. 2013 Oct 31;122(18):3165-8. doi: 10.1182/blood-2013-04-496893. Epub 2013 Sep 19.
- Individual participant dataSharing planned: No
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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.
Charles Kirkpatrick principal investigator
University of Colorado, Denver
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 Immune Deficiency, run by University of Colorado, Denver 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 2 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: status not confirmed, as of the sponsor's last update on 19 Apr 2022. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Charles Kirkpatrick ((303) 724-7197, charles.kirkpatrick@ucdenver.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Measurement of Serum immune globulin (time frame: each year for up to 20 years). The study lists 7 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 NCT03707782, which also lists 5 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 19 Apr 2022.