Cause of Unexplained Anaphylaxis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT00719719
Recruitment Status : Recruiting
First Posted : July 22, 2008
Last Update Posted : October 8, 2018
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) )

July 19, 2008
July 22, 2008
October 8, 2018
July 18, 2008
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  • Clinical samples obtained from the bone marrow biopsy and whole blood will be used to determine genetic and signaling abnormalities in mast cells and will be correlated with clinical features of idiopathic anaphylaxis. [ Time Frame: 11/01/19 ]
  • Clinical samples obtained from the bone marrow biopsy and whole blood will be used investigate the presence or absence of a monoclonal mast cell disorder. [ Time Frame: Ongoing ]
    Human mast cells will be also cultured from blood to search for functional and genetic abnormalities within the mast cell compartment that may correlate with clinical features of the disease.
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Complete list of historical versions of study NCT00719719 on Archive Site
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Cause of Unexplained Anaphylaxis
Studies in the Pathogenesis of Idiopathic Anaphylaxis

This study will explore the possible cause of unexplained, or idiopathic, anaphylaxis. Anaphylaxis is a rapid, life-threatening, severe reaction that occurs suddenly after contact with an allergy-causing substance, usually a particular food, drug or stinging insect. The allergen triggers mast cells to release several substances, including histamine. Histamine is responsible for many of the symptoms that may occur, such as flushing, hives, swelling of the palms and soles or tongue and vocal cords, nasal congestion, itching and tearing of the eyes, shortness of breath and wheezing, stomach pain, vomiting, low blood pressure, loss of consciousness, shock, and, rarely, death. Severe episodes of anaphylaxis are treated with epinephrine (adrenaline), followed by oral antihistamines and steroids. In more than half of cases of anaphylaxis, a clear cause is not identified. These cases are called idiopathic anaphylaxis. There is no cure or long-term preventive therapy for patients with recurrent episodes of idiopathic anaphylaxis.

People between 13 and 70 years of age who have idiopathic anaphylaxis, or have anaphylaxis that is caused by specific allergens such as food, venom, or drugs and medications may be eligible for this study.

Participants are evaluated at the NIH Clinical Center with the following tests and procedures:

  • Medical history, physical examination and blood tests.
  • Bone marrow biopsy. For this test, the skin over the hipbone and the outer surface of the hipbone itself are numbed with local anesthesia. Then, a needle is inserted into the hipbone and a small amount of bone marrow is drawn into a syringe. The needle also cuts a small core of bone marrow, which is removed for analysis.
  • Other tests that may be needed for evaluation of the patient s condition.

Anaphylaxis is a severe life-threatening systemic hypersensitivity reaction caused by release of mediators from mast cells and basophils, characterized by cutaneous, respiratory, cardiovascular, or gastrointestinal signs and symptoms. The most common specific causes of anaphylaxis are venom, drug, and food allergies (i.e. patients with specific anaphylaxis, SA), When a causative factor is not identified in patients are said to have idiopathic anaphylaxis (IA). Evidence of an underlying clonal mast cell disease has been found in about I in 15 patients with IA in our studies and in about 1 in 12 patientswith venom induced anaphylaxis in a European study. (1) The number of patients with anaphylaxis to foods or drugs who have a clonal mast cell disease is not known and the number or patients with venom induced anaphylaxis in the US with clonal mast cell disease has not been determined. Thus, a more complete understanding of the prevalence of clonal mast cell disease in those experiencing anaphylaxis and a better understanding of the associated laboratory abnormalities and disrupted molecular signaling pathways will have a substantial impact of the clinical management of patients who present with anaphylaxis.

This protocol thus focuses on determining the prevalence of clonal mast cell disorders in patients with the anaphylaxis, whether unexplained (IA) or associated with exposure to an antigen (SA), and attendant changes in the mast cell compartment. Subjects 13 - 70 years old will be evaluated to correlate both clinical and laboratory features of anaphylaxis and to identify genetic and molecular pathways that may predispose to these events. Subjects may undergo bone marrow examination in addition to supporting laboratory studies when indicated. We plan to enroll up to 200 subjects.

Observational Model: Case-Only
Time Perspective: Prospective
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*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
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  • Subjects must be at least 13 years of age and no older than 70 years of age.
  • Subjects with IA must have a diagnosis of anaphylaxis occurring in the absence of an identifiable provoking agent or stimulus by a referral provider. Patient may carry both the diagnosis of 1A and the diagnosis of SA.
  • Subjects with SA must have a history of a severe reaction to a venom, food or, drug confirmed when possible by relevant skin testing, challenge testing, RAST, immunoCAP, or ELISA. within the past 36 months.
  • Subject must have had a doctor s office or ER visit, or a hospitalization for evaluation for anaphylaxis and have a history of involvement of the skin and/or mucosal tissue (e.g., flushing, itching, hives, angioedema, tongue swelling), and at least one of the following:

    • Respiratory compromise (e.g., dyspnea, hoarseness-laryngeal edema, wheeze-bronchospasm, stridor, reduced peak expiratory flow, hypoxemia).
    • Gastrointestinal symptoms of vomiting and/or diarrhea
    • Reduced blood pressure and/or associated symptoms of end-organ dysfunction (as evidenced hypotonia, hypoxia, collapse, syncope or incontinence).
  • Letter of referral from prospective study participant's referring physician, or similar primary provider - with copies of available medical evaluation and laboratory studies
  • Able and willing to consider a bone marrow biopsy and aspirate


  • Presence of conditions which in the judgment of the investigator or the referring physician may put the subject at undue risk for travel (including frequent episodes of IA not preventable by pre-medication, acute infection, severe thrombocytopenia [minimum platelet count of 30,000], or significant cardiovascular disease)
  • Any condition that - in the view of the principal investigator would make the subject unsuitable for enrollment in this study
  • Inability to provide informed consent
  • Pregnancy
Sexes Eligible for Study: All
13 Years to 70 Years   (Child, Adult, Older Adult)
Contact: Hye Jeong C Bolan, R.N. (301) 594-1233
Contact: Melody C Carter, M.D. (301) 496-8772
United States
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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)
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Principal Investigator: Melody C Carter, M.D. National Institute of Allergy and Infectious Diseases (NIAID)
National Institutes of Health Clinical Center (CC)
September 4, 2018