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Cause of Unexplained Anaphylaxis

This study is currently recruiting participants.
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Verified March 17, 2017 by National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) )
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) ) Identifier:
First received: July 19, 2008
Last updated: June 20, 2017
Last verified: March 17, 2017

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 18 and 55 years of age who have idiopathic anaphylaxis episodes at least 6 times a year (with at least one episode every 3 months) 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.


Study Type: Observational
Study Design: Observational Model: Case-Only
Time Perspective: Prospective
Official Title: Studies in the Pathogenesis of Idiopathic Anaphylaxis

Resource links provided by NLM:

Further study details as provided by National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) ):

Primary Outcome Measures:
  • 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.

Estimated Enrollment: 100
Study Start Date: July 16, 2008
Detailed Description:

Anaphylaxis is a severe life-threatening systemic hypersensitivity reaction resulting from the release of mediators from mast cells and basophils, and is characterized by the presence of cutaneous, respiratory, cardiovascular, or gastrointestinal signs and symptoms. Although the most common causes of anaphylaxis are reactions to foods, pharmaceutical agents, and stinging insects, a causative factor is not identified in up to 50% of individuals with recurrent anaphylaxis. These individuals are thus said to have idiopathic anaphylaxis (IA). The mechanistic cause of IA remains uncertain, although elevated levels of urinary histamine, plasma histamine, and serum tryptase are consistent with mast cell activation.

This protocol will focus on the pathogenesis of IA. Subjects 13-70 years old with episodes of unexplained anaphylaxis will be evaluated in order to correlate both clinical and laboratory features that are typical of idiopathic anaphylaxis to identify genetic and molecular pathways that may predispose to these events and to determine signaling abnormalities in mast cells. We plan to enroll up to 100 subjects in this study. We anticipate that our findings will be a first step toward the development of novel targeted therapies.


Ages Eligible for Study:   13 Years to 60 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
  • Subject must be at least 13 years of age and no older than 70 years of age.
  • Diagnosis of anaphylaxis occurring in the absence of an identifiable provoking agent of stimulus (Idiopathic Anaphylaxis [IA]) by a referral physician. Patient may carry both the diagnosis of 1A and the diagnosis of anaphylaxis provoked by an identified stimulus.
  • History of anaphylaxis with a minimum of 3 episodes in the past year.
  • One doctor's office or ER visit or hospitalization for anaphylaxis without an established etiology with involvement of the skin and/or mucosal tissue (e.g., flushing, itching, hives, angioedema, tongue swelling) and at least one of the following:

    • Elevated serum tryptase above subject s baseline measurement within 6 hours of the event.
    • 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, 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 medical condition that in the view of the principal investigator would make the subject unsuitable for enrollment in this study (such as advanced renal disease).
  • Inability to provide informed consent.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT00719719

Contact: Hyejeong Bolan (301) 594-1233
Contact: Melody C Carter, M.D. (301) 496-8772

United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL)    800-411-1222 ext TTY8664111010   
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
Principal Investigator: Melody C Carter, M.D. National Institute of Allergy and Infectious Diseases (NIAID)
  More Information

Additional Information:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID) Identifier: NCT00719719     History of Changes
Other Study ID Numbers: 080184
Study First Received: July 19, 2008
Last Updated: June 20, 2017

Keywords provided by National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) ):
Mast Cell
Bone Marrow

Additional relevant MeSH terms:
Hypersensitivity, Immediate
Immune System Diseases processed this record on June 22, 2017