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The Mechanistic Biology of Primary Immunodeficiency Disorders

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ClinicalTrials.gov Identifier: NCT03394053
Recruitment Status : Recruiting
First Posted : January 9, 2018
Last Update Posted : December 14, 2018
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) )

Brief Summary:

Background:

Primary immunodeficiency disorders, or PIDs, are diseases that weaken the immune system. This makes it easier for a person to get sick. Some PIDs are mild and may not be diagnosed until later in life. Other kinds are severe and can be identified shortly after birth. Researchers want to learn more about PIDs by comparing data from relatives and healthy volunteers to people with a PID.

Objective:

To learn more about PIDs, including their genetic causes.

Eligibility:

People ages 0 75 with a PID or their healthy biological relatives the same ages

Healthy volunteers ages 18 75

Design:

Participants will be screened with a medical history, physical exam, and HIV blood test. They may have a pregnancy test.

Participants may repeat the screening tests.

Blood taken at screening will be used for genetic tests and research tests. Participants will be told test results that affect their health. Some blood will be stored for future research.

Adult participants with a PID may have a small piece of skin removed. The area will be numbed. A small tool will take a piece of skin about the size of a pencil eraser.

Researchers may collect fluid or tissue samples from PID participants regular medical care. They will use them for research tests.

Participants with a PID will have 3 follow-up visits over 10 years (for infants, 2 years). Visits will include a physical exam, medical history, and blood draw.

Participants with a PID and their relatives will be called once a year for 10 years. They will talk about how they are feeling and if they have developed any new symptoms or illnesses.


Condition or disease
Primary Immunodeficiency Disorders

Detailed Description:
This is a natural history study designed to investigate forms of primary immunodeficiency disorders (PIDs), and to better define both new and previously described forms of PID, including severe combined immunodeficiency (SCID), combined immunodeficiency, natural killer (NK) cell deficiency, and other disorders. Patients with clinical and/or laboratory evidence of PID will be recruited at Children s National Health System (CNHS) and the National Institute of Allergy and Infectious Diseases (NIAID). Infants identified at birth with a positive newborn screening for SCID and confirmed to have T-cell lymphocytopenia will also be recruited at CNHS. Subjects with a known or unknown PID and infants with T-cell lymphocytopenia will provide one or more blood donations during the course of the study to enable immunologic and genetic investigations of immune pathways contributing to PIDs. These subjects will also be followed clinically to longitudinally assess the natural history of novel and known PIDs. Subjects will be followed over time with regard to their immunologic phenotype, clinical disease (including incidence of infections, autoimmune phenomena, allergic disease, or malignancies), and response to both preventative and definitive therapies. Biological relatives who do not have PID and healthy adult volunteers will also be eligible to serve as controls for this study.

Study Type : Observational
Estimated Enrollment : 1100 participants
Observational Model: Family-Based
Time Perspective: Prospective
Official Title: The Mechanistic Biology of Primary Immunodeficiency Disorders
Actual Study Start Date : May 30, 2018
Estimated Primary Completion Date : December 31, 2037
Estimated Study Completion Date : December 31, 2039


Group/Cohort
1
People ages 0 75 with a PID
2
Healthy biological relatives the same ages
3
Healthy volunteers ages 18 75



Primary Outcome Measures :
  1. Identification of genetic variants that are associated with PID [ Time Frame: end of accrual period of 8 years ]
  2. Identification of unique clinical phenotypes associated with known genetic causes of PID [ Time Frame: end of accrual period of 8 years ]

Secondary Outcome Measures :
  1. Identification of phenotypic, molecular, and functional abnormalities associated with known or novel forms of PID. [ Time Frame: the end of 15 year period from start of protocol ]
  2. Incidence of infection and autoimmune disease; incidence of allergic disorders, incidence of malignancies and overall survival [ Time Frame: the end 15 year period from start of protocol ]
  3. Impact of both preventive and definitive treatments on event-free survival (as defined by survival in absence of invasive or chronic infection, autoimmunity, or malignancies). [ Time Frame: the end of 15 year perios from start of protocol ]


Information from the National Library of Medicine

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Ages Eligible for Study:   up to 75 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Patients with clinical and/or laboratory evidence of PID will be recruited .
Criteria
  • INCLUSION CRITERIA:

    1. Subjects must meet one of the following 4 criteria:

      1. Patients (age 0-75 years) with a clinical diagnosis of a form of PID (either known or unknown). PID is defined by laboratory and/or clinical findings on two or more occasions that are consistent with a defect in innate or adaptive immunity. Specific PIDs are defined by the International Union of Immunological Societies guidelines. These subjects must also be willing to undergo genetic testing and to allow their biospecimens to be modified into iPS cells. Women of childbearing potential, or who are pregnant or lactating, may be eligible. The volume of blood collected for research purposes will be reduced, and no skin biopsies will be performed for research purposes in consideration of their safety.
      2. Infants identified at birth with positive newborn screening for SCID and confirmed to have T-cell lymphocytopenia. These subjects must be willing to undergo genetic testing.
      3. Biological relatives (age 0-75 years) of a subject who meets criterion 1a or 1b but who do not have a PID themselves. All relatives must be willing to undergo genetic testing. Women of childbearing potential, or who are pregnant or lactating, may be eligible. The volume of blood collected for research purposes will be reduced in consideration of their safety.
      4. Healthy volunteers (age 18-75 years) who are not related to another study subject, who do not have a PID, whose weight is greater than 110 pounds, do not have a history of any heart, lung, or kidney disease, or bleeding disorders, do not have a history of viral hepatitis (B or C), and have a negative HIV screening test.
    2. All subjects must be willing to allow their samples to be stored for future research.

EXCLUSION CRITERIA:

  1. Subjects with secondary causes of immunodeficiency are excluded from this study. Secondary causes of immunodeficiency include HIV infection and immunodeficiency that is deemed to be secondary to chronic use of immunosuppressive medications or chemotherapeutic agents.
  2. Any condition that, in the opinion of the investigator, contraindicates participation in this study.

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): NCT03394053


Contacts
Contact: Luigi D Notarangelo, M.D. (301) 761-7550 luigi.notarangelo2@nih.gov

Locations
United States, District of Columbia
Division of Allergy & Immunology Children's Hospital (CNHS) Recruiting
Washington, District of Columbia, United States, 20010
Contact: Michael Keller, M.D.    202-476-5843    mkeller@childrensnational.org   
United States, Maryland
National Institutes of Health Clinical Center Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)    800-411-1222 ext TTY8664111010    prpl@cc.nih.gov   
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
Investigators
Principal Investigator: Luigi D Notarangelo, M.D. National Institute of Allergy and Infectious Diseases (NIAID)

Additional Information:
Publications:
Stray-Pedersen A, Sorte HS, Samarakoon P, Gambin T, Chinn IK, Coban Akdemir ZH, Erichsen HC, Forbes LR, Gu S, Yuan B, Jhangiani SN, Muzny DM, Rødningen OK, Sheng Y, Nicholas SK, Noroski LM, Seeborg FO, Davis CM, Canter DL, Mace EM, Vece TJ, Allen CE, Abhyankar HA, Boone PM, Beck CR, Wiszniewski W, Fevang B, Aukrust P, Tjønnfjord GE, Gedde-Dahl T, Hjorth-Hansen H, Dybedal I, Nordøy I, Jørgensen SF, Abrahamsen TG, Øverland T, Bechensteen AG, Skogen V, Osnes LTN, Kulseth MA, Prescott TE, Rustad CF, Heimdal KR, Belmont JW, Rider NL, Chinen J, Cao TN, Smith EA, Caldirola MS, Bezrodnik L, Lugo Reyes SO, Espinosa Rosales FJ, Guerrero-Cursaru ND, Pedroza LA, Poli CM, Franco JL, Trujillo Vargas CM, Aldave Becerra JC, Wright N, Issekutz TB, Issekutz AC, Abbott J, Caldwell JW, Bayer DK, Chan AY, Aiuti A, Cancrini C, Holmberg E, West C, Burstedt M, Karaca E, Yesil G, Artac H, Bayram Y, Atik MM, Eldomery MK, Ehlayel MS, Jolles S, Flatø B, Bertuch AA, Hanson IC, Zhang VW, Wong LJ, Hu J, Walkiewicz M, Yang Y, Eng CM, Boerwinkle E, Gibbs RA, Shearer WT, Lyle R, Orange JS, Lupski JR. Primary immunodeficiency diseases: Genomic approaches delineate heterogeneous Mendelian disorders. J Allergy Clin Immunol. 2017 Jan;139(1):232-245. doi: 10.1016/j.jaci.2016.05.042. Epub 2016 Jul 16. Erratum in: J Allergy Clin Immunol. 2018 Feb;141(2):832.

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT03394053     History of Changes
Other Study ID Numbers: 180041
18-I-0041
First Posted: January 9, 2018    Key Record Dates
Last Update Posted: December 14, 2018
Last Verified: December 4, 2018

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) ):
PID
Immune Deficiency
Molecular Biology
T-Cell Lymphocytopenia
Genetic Biology

Additional relevant MeSH terms:
Disease
Immunologic Deficiency Syndromes
Pathologic Processes
Immune System Diseases