Clinical Trials Logo

Clinical Trial Summary

This study will examine the safety and effectiveness of ranitidine (Zantac) in patients with Hyper-IgE recurrent infection syndrome, a disease characterized by recurrent infections of the ears, sinuses, lungs and skin, and abnormal levels of the antibody immunoglobulin E (IgE).

Patients age 2 and older who have Hyper-IgE recurrent infection syndrome and who have had chronic or frequent infections in the last 12 months may be eligible for this study.

Participants are randomly assigned to take ranitidine or placebo in pill or liquid form twice a day for 12 months. In addition to treatment, patients undergo the following procedures during visits scheduled on day 0 of the study (baseline) and at 3, 12, 15 and 24 months. Evaluations at 6, 9, 18 and 21 months are by telephone.

- Medical history and physical examination - baseline and 3 and 24 months.

- Clinical severity score - baseline and 3, 6, 9, 12, 15, 18, 21 and 24 months.

- Dermatology exam - baseline and 3, 12, 15 and 24 months.

- Pulmonary function test - baseline and 12 and 24 months.

- Chest CT - baseline and 12 and 24 months.

- Quality of life assessment - baseline and 3, 12, 15 and 24 months.

- Pregnancy testing - baseline and 3, 12, 15 and 24 months.

- HIV test - baseline and 12 and 24 months.

- Contraception evaluation - baseline and 3, 6, 9, 12, 15, 18, 21 and 24 months.

- Missed school/work days assessment - baseline and 3, 12, 15 and 24 months.

- Medication adherence - baseline and 3, 6, 9, 12, 15, 18, 21 and 24 months.

In addition to the above procedures, participants who are not enrolled in study 00-I-0159 have a baseline scoliosis series and genetic consult.


Clinical Trial Description

Hyper-immunoglobulin E (IgE) syndrome (HIES) is a rare primary immunodeficiency characterized by eczema, recurrent skin and lung infections, elevated serum IgE, and multiple connective tissue and skeletal abnormalities. The autosomal dominant form of HIES is caused primarily by a mutation in the STAT3 gene. Patients with HIES produce IgE antibodies specific for Candida albicans and Staphylococcus aureus, two of the common pathogens in this population. We hypothesize that the presence of pathogen-specific IgE, combined with continuous exposure to these ubiquitous agents, leads to chronic IgE-mediated histamine release from basophils and mast cells, with subsequent pathogen-specific immune tolerance and an increase in pathogen-specific T regulatory cells. We plan to test this hypothesis through clinical and immunologic evaluation of HIES patients before, during, and after histamine-2 receptor (H2) blocker therapy with ranitidine through a prospective, placebo-controlled crossover study. We chose this therapy because histamine has been shown to stimulate interleukin-10 (IL-10), a major down regulatory cytokine, through the H2 receptor, and clinical improvement has been observed in several patients treated with H2 blockers. Laboratory studies will include determinations of pathogen-specific immunoglobulin G4 (IgG4):IgE ratios, basophil activation, IL-10 producing regulatory T-cells, cellular proliferative responses to staphylococcal and candidal antigens, and functional testing of regulatory T-cells. Clinical evaluations will include comprehensive history and physical examination, dermatologic evaluation, genetic evaluation for clinical severity scoring of HIES, pulmonary function tests, and chest computerized tomography (CT) examination. Through this study, we will further our understanding of the immunologic abnormalities of HIES and determine whether a larger prospective, double-blind trial of H2 blockade as adjunctive therapy for HIES is indicated. ;


Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment


Related Conditions & MeSH terms


NCT number NCT00527878
Study type Interventional
Source National Institutes of Health Clinical Center (CC)
Contact
Status Terminated
Phase Phase 2
Start date September 2007
Completion date June 2011

See also
  Status Clinical Trial Phase
Completed NCT04643639 - Assessing the Effects of CytoSorb Hemoperfusion on the Development on Immunoparalysis Phase 3
Completed NCT05256784 - Mountain Food and Natural Probiotic in Nutrition
Recruiting NCT04448951 - Immune Homeostasis in Sepsis and Septic Shock
Recruiting NCT03721146 - ENCAPSID Study : ENCApsulated Bacterial Infection and Primary, Secondary ImmunoDeficiency
Not yet recruiting NCT06089174 - Assessment of the Increased Risk of Infection Following an Ultratrail N/A
Completed NCT02895204 - Effect of Fermented Maillard Reacted Whey Protein on Immune Function N/A
Recruiting NCT03707782 - Mechanisms of Immune Deficiency
Recruiting NCT06332196 - Immunodeficiency and Cancer: Identification of Congenital Immune System Defects Underlying Paediatric Lymphomas N/A
Recruiting NCT04646525 - The Relationship Between Covid-19 Infection in Pediatric Patients and Secondary Lymphoid Organs
Active, not recruiting NCT00852943 - Screening Protocol for Genetic Diseases of Allergic Inflammation
Completed NCT03609840 - Study of Thiotepa and TEPA Drug Exposure in Pediatric Hematopoietic Stem Cell Transplant Patients
Not yet recruiting NCT01359384 - Bronchial Inflammation in Patients With Severe Immune Deficiency Under Immunoglobulin Treatment N/A
Recruiting NCT05605808 - Aerobic Training and Diet on the Immune System in Postmastectomy Patients Receiving Chemotherapy N/A
Completed NCT03899480 - Adoptive Transfer of Haploidentical NK Cells and N-803 Phase 1
Completed NCT03051425 - Immune Benefits of Consumption of Dairy Yogurt in Elderly N/A
Active, not recruiting NCT04824651 - Covid-19 Vaccine Cohort in Specific Populations
Enrolling by invitation NCT04382508 - Coronavirus Infection in Primary or Secondary Immunosuppressed Children and Adults.
Completed NCT02334943 - Immune Activation in HIV-1 Infected Patients Under AntiRetroviral Treatment N/A
Completed NCT03052491 - Effects of a 10 Component Dietary Supplement on Health and the Quality of Life N/A
Completed NCT03881566 - Presepsin as Detective Marker of Sepsis in Immunodeficiency ICU Patients