Effect of Ranitidine on Hyper-IgE Recurrent Infection (Job's) Syndrome

NCT00527878 | Terminated Phase 2 Results

• 2 other identifiers: 07021807-I-0218
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

JOB's Syndrome; Hyper-IgE Recurrent Infection Syndrome; Immune Deficiency

Keywords

Hyper-IgE Recurrent Infection Syndrome; Ranitidine Therapy; Job's Syndrome; Cross-Over Study; Double-Blind Placebo Controlled; Hyper-IgE Syndrome; Job Syndrome; Immune Deficiency

Outcome Measures

Primary Outcomes (1)

• Number of Infections in Subjects With HIES.

  Patients received one year of treatment medication and one year of placebo. New infections (bacterial, fungal, viral or parasitic) were defined as those requiring an addition or change of an antimicrobial (including topical, oral or intravenous therapies) or those requiring a medical procedure (i.e., incision and drainage of a skin abscess, warm soaks to aid abscess drainage or sinus drainage).

  1 year on intervention

Secondary Outcomes (3)

• New Skin Infections

  12 months placebo/12 months ranitidine

• New Lung Infections

  12 months placebo and 12 months ranitidine

• Clinical Severity Score

  one year on ranitidine and one year on placebo

Study Arms (2)

Placebo/Ranitidine crossover

EXPERIMENTAL

Patients took placebo for 12 months and then ranitidine for 12 months

Drug: Ranitidine; Drug: Placebo

Ranitidine/placebo crossover

EXPERIMENTAL

Ranitidine for one year followed by placebo for one year

Drug: Ranitidine; Drug: Placebo

Interventions

Ranitidine DRUG

Double blinded, randomized placebo controlled crossover study. Patients received 12 months of placebo and 12 months of treatment medication (ranitidine).

Placebo/Ranitidine crossover; Ranitidine/placebo crossover

Placebo DRUG

Placebo/Ranitidine crossover; Ranitidine/placebo crossover

Eligibility Criteria

• Age: 2 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female patients with the diagnosis of Hyper IgE Recurrent Infection (Job) syndrome. Mutations in the STAT3 gene account for the majority, if not all cases of HIES. However as the full genetics of HIES remains unknown, we will use clinical criteria, including the expert opinion of the investigators, as well as a score greater than 40 by the diagnostic scoring system used in protocol 00-I-0159.
• A chronic (greater than 4 weeks duration) infection or greater than 2 acute infections within the last 12 months. Acute infections can include but are not limited to: pneumonia, abscesses, sinusitis, skin infections, mucocutaneous candidiasis and ear infections. Chronic infections include continuous or intermittent symptoms despite appropriate therapeutic interventions for at least 4 weeks, including but not limited to chronic lung infiltrates with productive cough, chronic ear drainage despite topical therapy, chronic or intermittent drainage from a single abscess site, and/or chronic signs of sinusitis on sinus CT scan.
• Patients have to be at their own personal clinical baseline for at least 2 weeks duration. Patients will not start the study medication during an acute exacerbation of and infection.
• The patient or the patient's guardian will be willing and capable of providing informed consent after initial counseling by clinical staff. Separate consent forms for all interventional procedures will be obtained after explanation of the specific procedure.
• Patients must agree to have blood stored for future studies of the immune system and/or other medical conditions.
• Women of childbearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation.
• Patients may be concurrently enrolled on other protocols as long as the Principal Investigator (PI) is informed.

You may not qualify if:

• Pregnancy. Ranitidine is pregnancy class B, and likely safe in pregnancy, but as this has not been studied, pregnant patients will be excluded. In addition, hormonal changes that occur during pregnancy may affect the skin manifestations and frequency of infection.
• Hypersensitivity to ranitidine or any of the ingredients in ranitidine.
• Pre-existing medications or conditions for which the investigators judge that ranitidine should not be given.
• Patient or investigators unwilling to stop baseline H2 receptor antagonist therapy (over the counter or prescription) such as Tagamet (Cimetidine), Pepcid (Famotidine), and Axid (Nizatidine). H2 receptor antagonist therapy must be stopped for 3 months prior to study initiation. Patients who are receiving H2 receptor antagonist therapy for gastritis, acid reflux, or peptic ulcer disease will be offered changing their regimen to a proton pump inhibitor or other non-H2 receptor antagonist therapy to allow for study enrollment (3 months after stopping the H2 receptor antagonist).
• Patients under the age of 2 years
• Patients with HIV, receiving chemotherapy or who have a malignancy.
• Any condition that in the judgment of the investigator would place the subject at undue risk or compromise the results or interpretation of the study.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Grimbacher B, Holland SM, Gallin JI, Greenberg F, Hill SC, Malech HL, Miller JA, O'Connell AC, Puck JM. Hyper-IgE syndrome with recurrent infections--an autosomal dominant multisystem disorder. N Engl J Med. 1999 Mar 4;340(9):692-702. doi: 10.1056/NEJM199903043400904.

  PMID: 10053178 BACKGROUND

• Davis SD, Schaller J, Wedgwood RJ. Job's Syndrome. Recurrent, "cold", staphylococcal abscesses. Lancet. 1966 May 7;1(7445):1013-5. doi: 10.1016/s0140-6736(66)90119-x. No abstract available.

  PMID: 4161105 BACKGROUND

• Buckley RH, Wray BB, Belmaker EZ. Extreme hyperimmunoglobulinemia E and undue susceptibility to infection. Pediatrics. 1972 Jan;49(1):59-70. No abstract available.

  PMID: 5059313 BACKGROUND

MeSH Terms

Conditions

Job Syndrome; Immunologic Deficiency Syndromes

Interventions

Ranitidine

Condition Hierarchy (Ancestors)

Phagocyte Bactericidal Dysfunction; Leukocyte Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Primary Immunodeficiency Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Immune System Diseases

Intervention Hierarchy (Ancestors)

Furans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Alexandra Freeman MD, Staff Clinician, Lead Associate Investigator for Protocol
• Organization: NIAID, NIH

freemaal@mail.nih.gov

301-594-9045

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: NIH

Study Record Dates

• First Submitted: September 8, 2007
• First Posted: September 11, 2007
• Study Start: September 1, 2007
• Primary Completion: June 1, 2011
• Study Completion: June 1, 2011
• Last Updated: February 4, 2013
• Results First Posted: February 4, 2013

Record last verified: 2013-02

Locations

US (1)