Comment Period Extended to 3/23/2015 for Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Study of Clinical Features and Genetics of Hyperimmunoglobulin E Recurrent Infection

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2015 by National Institutes of Health Clinical Center (CC)
Sponsor:
Collaborator:
Albert Einstein College of Medicine of Yeshiva University
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) )
ClinicalTrials.gov Identifier:
NCT00006150
First received: August 8, 2000
Last updated: January 17, 2015
Last verified: January 2015

August 8, 2000
January 17, 2015
August 2000
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Complete list of historical versions of study NCT00006150 on ClinicalTrials.gov Archive Site
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Study of Clinical Features and Genetics of Hyperimmunoglobulin E Recurrent Infection
Natural History, Management, and Genetics of the Hyperimmunoglobulin E Recurrent Infection Syndrome (HIES)

The Hyper IgE Syndromes (HIES) are primary immunodeficiencies resulting in eczema and recurrent skin and lung infections. Autosomal dominant Hyper IgE syndrome (AD-HIES; Job's syndrome) is caused by STAT3 mutations, and is a multisystem disorder with skeletal, vascular, and connective tissue manifestations. Understanding how STAT3 mutations cause these diverse clinical manifestations is critical to our complete understanding of bone metabolism, bronchiectasis, dental maturation, and atherosclerosis. Mutations in DOCK8 cause many cases of autosomalrecessive Hyper IgE syndrome. These individuals suffer from extensive viral infections as well as have a high incidence of malignancy and mortality. The pathogenesis of this disease is being investigated. Therefore, we seek to enroll patients and families with a confirmed or suspected diagnosis of HIES syndrome for extensive phenotypic and genotypic study as well as disease management. Patients will be carefully examined by a multidisciplinary team and followed longitudinally. Through these studies we hope to better characterize the clinical presentation of HIES and to be able to identify further genetic etiologies, as well as understand the pathogenesis of HIES. We seek to enroll 200 patients and 300 relatives.

The Hyper IgE Syndromes (HIES) are primary immunodeficiencies resulting in eczema and recurrent skin and lung infections. Autosomal dominant Hyper IgE syndrome (AD-HIES; Job's syndrome) is caused by STAT3 mutations, and is a multisystem disorder with skeletal, vascular, and connective tissue manifestations. Understanding how STAT3 mutations cause these diverse clinical manifestations is critical to our complete understanding of bone metabolism, bronchiectasis, dental maturation, and atherosclerosis. Mutations in DOCK8 cause many cases of autosomalrecessive Hyper IgE syndrome. These individuals suffer from extensive viral infections as well as have a high incidence of malignancy and mortality. The pathogenesis of this disease is being investigated. Therefore, we seek to enroll patients and families with a confirmed or suspected diagnosis of HIES syndrome for extensive phenotypic and genotypic study as well as disease management. Patients will be carefully examined by a multidisciplinary team and followed longitudinally. Through these studies we hope to better characterize the clinical presentation of HIES and to be able to identify further genetic etiologies, as well as understand the pathogenesis of HIES. We seek to enroll 200 patients and 300 relatives.

Observational
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Job's Syndrome
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*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
500
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  • INCLUSION CRITERIA:

Patients must be referred to the NIH with a diagnosis or a suspicion of Hyper IgE syndrome. Family members of probands and patients referred for other immune syndromes that demonstrate some of the characteristics of HIES may also be evaluated under this protocol. Male and female patients will be accepted. An inclusion age range will be constructed to accommodate at-risk infants born into affected families as well as to be able to examine the members of extended families. The extent of evaluation will be tailored to the patient s needs, age, and conditions. The cutaneous manifestations of HIE are often present at birth and need management from that time on.

Because this is often an AD disorder, it is important to evaluate family members. Family members will have labs drawn for genetic testing and additional labs as clinically indicated. Selected family members will have EBV cell lines made and all family members will receive a genetic-oriented physical examination with close examination of their palates, hyper-extensibility, etc. If on this evaluation any information is uncovered which suggests abnormalities related to Hyper IgE syndrome, then further workup would include chest X-ray or CT, possible spine films, dental evaluation, dermatology consult, and other consults or procedures deemed necessary for that particular relative. For the recessive forms of HIES, such as DOCK8 deficiency and PGM3 deficiency, family members may be evaluated as possible donors if a hematopoietic stem cell

transplant is necessary.

EXCLUSION CRITERIA:

Pregnant women are excluded only from any procedure or test that may endanger the pregnancy or the fetus due to the risk from radiographic studies, anesthesia, or certain biopsies.

Coronary CT angiography will not be performed on any patient with contraindication to IV contrast media. This includes patients with: 1) creatinine value of greater than 1.3 mg/dl, 2) history of multiple myeloma, 3) use of metformin-containing products less than 24 hours prior to contrast media, and 4) history of significant allergic reaction to CT contrast agents despite the use of premedication.

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Contact: Pamela A Welch, R.N. (301) 402-0449 welchp@mail.nih.gov
Contact: Alexandra Freeman, M.D. (301) 594-9045 freemaal@mail.nih.gov
United States
 
NCT00006150
000159, 00-I-0159
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National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) )
National Institute of Allergy and Infectious Diseases (NIAID)
Albert Einstein College of Medicine of Yeshiva University
Principal Investigator: Alexandra Freeman, M.D. National Institute of Allergy and Infectious Diseases (NIAID)
National Institutes of Health Clinical Center (CC)
January 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP