Effect of Ranitidine on Hyper-IgE Recurrent Infection (Job's) Syndrome
Condition: JOB's Syndrome; Hyper-IgE Recurrent Infection Syndrome; Immune Deficiency
MeSH terms: Infections; Job Syndrome; Immunologic Deficiency Syndromes; Syndrome; Recurrence; Reinfection
Intervention: Ranitidine; Placebo
Intervention description: Double blinded, randomized placebo controlled crossover study. Patients received 12 months of placebo and 12 months of treatment medication (ranitidine).
Intervention MeSH terms: Ranitidine; Ranitidine bismuth citrate
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 16.0
Sex: All
Minimum age: 2 Years
Healthy volunteers: No
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

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.
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

               1. 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.

               2. 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.

               3. Patients aged 2 years and above. There is no upper age limit. We are excluding
                  children less than 2 years of age, as we do not expect them to meet the first
                  inclusion criterion, having a score high enough to be diagnosed with HIES.

               4. 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.

               5. 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.

               6. Patients must agree to have blood stored for future studies of the immune system
                  and/or other medical conditions.

               7. 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.

               8. Patients may be concurrently enrolled on other protocols as long as the Principal
                  Investigator (PI) is informed.

        EXCLUSION CRITERIA:

          1. 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.

          2. Hypersensitivity to ranitidine or any of the ingredients in ranitidine.

          3. Pre-existing medications or conditions for which the investigators judge that
             ranitidine should not be given.

          4. 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).

          5. Patients under the age of 2 years

          6. Patients with HIV, receiving chemotherapy or who have a malignancy.

          7. 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.