ClinicalTrials.gg
CompletedNCT00719719Updated Oct 2, 2026

Cause of Unexplained Anaphylaxis

An observational study in Idiopathic Anaphylaxis, Drug Anaphylaxis and Venom Anaphylaxis, sponsored by National Institute of Allergy and Infectious Diseases (NIAID). Completed at 1 site in United States. Open to participants aged 13 Years to 75 Years. Per ClinicalTrials.gov, last updated 2026-10-02.

Sponsored by National Institute of Allergy and Infectious Diseases (NIAID) · Observational

Study type
Observational
Model
Case-only
Time perspective
Prospective
Enrollment
115
Ages
13 Years to 75 Years
Sex
All
01

Study summary

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.
Read the detailed description

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 - 75 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.

02

Conditions studied

  • Idiopathic Anaphylaxis
  • Drug Anaphylaxis
  • Venom Anaphylaxis
  • Food Anaphylaxis

Keywords

  • Antigen Specific
  • Mast Cell
  • Tryptase
  • Bone Marrow
  • Hives
  • Natural History
  • Anaphylaxis
03

In context

Urticaria

147 studies on the registry are indexed under Urticaria; 19 are open to participants now.

This study's enrollment of 115 is below the median of 220 across 35 observational studies indexed under Urticaria.

Browse Urticaria studies →

Lead sponsor

National Institute of Allergy and Infectious Diseases (NIAID) is the lead sponsor of 2,446 studies on the registry; 179 are open to participants now.

Of its 405 completed or terminated interventional studies of FDA-regulated products, 302 (75%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
13 Years to 75 Years
Sexes eligible
All
Accepts healthy volunteers
No
Sampling method
Non-probability sample

Study population

Primary Clinical

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

  • Subjects must be at least 13 years of age and no older than 75 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 and aspirate

Exclusion criteria

EXCLUSION CRITERIA:

  • 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 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
  • Pregnancy
Terms in these criteria, in plain language(3)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

Biopsy and archival tissue

A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.

Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.

Platelets

Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.

Informed consent

Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.

You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.

05

Study design

Observational model
Case-only
Time perspective
Prospective
Enrollment
115 participants (actual)

Groups and cohorts

  • Drug Anaphylaxis

    Drug Anaphylaxis

  • Food Anaphylaxis

    Food Anaphylaxis

  • Idiopathic Anaphylaxis

    Idiopathic Anaphylaxis

  • Venom Anaphylaxis

    Venom Anaphylaxis

06

What researchers measure

Primary outcomes

  1. The primary objective of this study is to determine if patients with anaphylaxis (IA or SA) have clinical & laboratory features that correlate with genetic or molecular abnormalities in their mast cell population including the presence o...

    The primary objective of this study is to determine if patients with anaphylaxis (IA or SA) have clinical \& laboratory features that correlate with genetic or molecular abnormalities in their mast cell population including the presence of clonal mast cell disease.

    Time frame: 12/31/2028

Secondary outcomes

  1. Explore abnormalities in signaling Evaluate growth and degranulation of mast cells grown in vitro. Identify patients with the D816V mutation

    Explore abnormalities in signaling Evaluate growth and degranulation of mast cells grown in vitro. Identify patients with the D816V mutation

    Time frame: 12/31/2028

07

Study locations

1 site
  • National Institutes of Health Clinical Center
    Bethesda, Maryland 20892, United States
08

References and documents

Publications

  • Sampson HA, Munoz-Furlong A, Campbell RL, Adkinson NF Jr, Bock SA, Branum A, Brown SG, Camargo CA Jr, Cydulka R, Galli SJ, Gidudu J, Gruchalla RS, Harlor AD Jr, Hepner DL, Lewis LM, Lieberman PL, Metcalfe DD, O'Connor R, Muraro A, Rudman A, Schmitt C, Scherrer D, Simons FE, Thomas S, Wood JP, Decker WW. Second symposium on the definition and management of anaphylaxis: summary report--second National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network symposium. Ann Emerg Med. 2006 Apr;47(4):373-80. doi: 10.1016/j.annemergmed.2006.01.018. PubMed 16546624 ↗
  • Webb LM, Lieberman P. Anaphylaxis: a review of 601 cases. Ann Allergy Asthma Immunol. 2006 Jul;97(1):39-43. doi: 10.1016/S1081-1206(10)61367-1. PubMed 16892779 ↗
  • Patterson R, Hogan MB, Yarnold PR, Harris KE. Idiopathic anaphylaxis. An attempt to estimate the incidence in the United States. Arch Intern Med. 1995 Apr 24;155(8):869-71. doi: 10.1001/archinte.155.8.869. PubMed 7717796 ↗

Individual participant data

Plan to share: Undecided — The initial hypothesis for this protocol has already been explored and published. The ongoing hypothesis generated with the expansion of the protocol is ongoing and once data collection is at a level for analysis, we will include in the IPD.

09

Timeline

1 registry update since Sep 25, 2026

Started Nov 2008 (actual).

How these figures are worked out, and which studies are left out of them.

Registered
Jul 19, 2008
First posted
Jul 22, 2008
StartActual
Nov 5, 2008
Last update
Oct 2, 2026
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
Minor edits
Nothing that changes what the study is or who can join. Edited: verification date
1 update, last Oct 2, 2026
Show all 1 update
  1. Oct 2, 2026
    Minor edits only
    + 1 other change: verification date

From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗

10

Registry details

Key details

Study ID
NCT00719719
Responsible party
Sponsor
First posted
Jul 22, 2008
Start date
Nov 5, 2008
Last update
Oct 2, 2026

Study contacts

Pamela A Frischmeyer-Guerrerio, M.D.
principal investigator · National Institute of Allergy and Infectious Diseases (NIAID)

Oversight

FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Sep 2026. You cannot join it, but the record below documents what was studied.

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Discussion

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