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Mechanisms of Immune Deficiency

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ClinicalTrials.gov Identifier: NCT03707782
Recruitment Status : Recruiting
First Posted : October 16, 2018
Last Update Posted : June 10, 2021
Sponsor:
Collaborator:
Colorado Clinical & Translational Sciences Institute
Information provided by (Responsible Party):
University of Colorado, Denver

Study Description
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Brief 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.
    2. 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.


Condition or disease
Immune Deficiency

Detailed Description:

The experiments that are proposed in this portion of the study are intended to:

  1. 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.
  2. characterize the current status of B-cell maturation and function in subjects with either the variant gene and the wild type gene.
  3. 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
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Study Type : Observational
Estimated Enrollment : 200 participants
Observational Model: Family-Based
Time Perspective: Prospective
Official Title: Mechanisms of Immune Deficiency
Actual Study Start Date : October 20, 2020
Estimated Primary Completion Date : December 2021
Estimated Study Completion Date : December 2021
Groups and Cohorts
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Group/Cohort
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


Outcome Measures
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Primary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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

  5. 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

  6. 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

  7. 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


Biospecimen Retention:   Samples With DNA
Blood lymphocytes, serum and plasma other tissue if availale

Eligibility Criteria
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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Individuals aged 18 years or older and have an immune deficiency or are related to a person who has an immune deficiency.
Criteria

Inclusion Criteria:

  1. Immunodeficiency disease; or
  2. family member of individual with immunodeficiency disease

Exclusion Criteria:

  1. Persons with immune deficiencies that are secondary to other diseases such as malignancies.
  2. Persons who do not have immune deficiencies, persons who are not meet eligibility criteria
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03707782


Contacts
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Contact: Charles Kirkpatrick (303) 724-7197 charles.kirkpatrick@ucdenver.edu

Locations
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United States, Colorado
UColorado Recruiting
Denver, Colorado, United States, 80045
Contact: Charles H Kirkpatrick, MD    303-724-7197    charles.kirkparick@ucdenver.edu   
Sponsors and Collaborators
University of Colorado, Denver
Colorado Clinical & Translational Sciences Institute
Investigators
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Principal Investigator: Charles Kirkpatrick University of Colorado, Denver
More Information
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Publications:

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Responsible Party: University of Colorado, Denver
ClinicalTrials.gov Identifier: NCT03707782    
Other Study ID Numbers: 18-0337
First Posted: October 16, 2018    Key Record Dates
Last Update Posted: June 10, 2021
Last Verified: June 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Immunologic Deficiency Syndromes
Immune System Diseases