Idiopathic AnaphylaxisNCT00719719
Cause of Unexplained Anaphylaxis
An observational study of Idiopathic Anaphylaxis and Drug Anaphylaxis, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 13 to 75 years
- Conditions the study is for
- Idiopathic Anaphylaxis, Drug Anaphylaxis, Venom Anaphylaxis
- How many people
- 115 participants
- Where
- 1 siteUnited States
- Study dates
- 5 Nov 2008to not given
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 13 to 75 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Primary Clinical
Who may be able to join
- 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
Show all 9Show fewer
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
Official title: Studies in the Pathogenesis of 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.
Read more
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.
- Keywords
- Antigen Specific, Mast Cell, Tryptase, Bone Marrow, Hives, Natural History, Anaphylaxis
- Medical subject headings
- Urticaria, Anaphylaxis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Drug Anaphylaxis | Drug Anaphylaxis | |
| Food Anaphylaxis | Food Anaphylaxis | |
| Idiopathic Anaphylaxis | Idiopathic Anaphylaxis | |
| Venom Anaphylaxis | Venom Anaphylaxis |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Measured: 12/31/2028
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jul 2008 (estimated)
- Study start5 Nov 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Idiopathic AnaphylaxisStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case only
- Time perspective
- Prospective
- Enrolment
- 115 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Pamela A Frischmeyer-Guerrerio, M.D., Principal investigator, National Institute of Allergy and Infectious Diseases (NIAID)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00719719
- Sponsor's protocol ID
- 080184
- Other IDs
- 08-I-0184
- Status last verified
- 30 Sep 2026
- First submitted
- 19 Jul 2008
- Last updated
- 2 Oct 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- 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.
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 16546624Webb 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 16892779Patterson 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
Study at a glance
From the registry record, last updated by the sponsor on 2 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Studies in the Pathogenesis of Anaphylaxis
- ClinicalTrials.gov ID
- NCT00719719
- Acronym / sponsor ID
- 080184
- Keywords
- Antigen Specific, Mast Cell, Tryptase, Bone Marrow, Hives, Natural History, Anaphylaxis
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 115 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- 5 Nov 2008 (actual)
- First posted
- 22 Jul 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Observational model
- Case only
- Time perspective
- Prospective
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Drug Anaphylaxis | – | –Drug Anaphylaxis |
| Food Anaphylaxis | – | –Food Anaphylaxis |
| Idiopathic Anaphylaxis | – | –Idiopathic Anaphylaxis |
| Venom Anaphylaxis | – | –Venom Anaphylaxis |
Who may qualify
- Ages
- 13 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Primary Clinical
Key inclusion criteria (9 listed)
- 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:
- Letter of referral from prospective study participant's referring physician, or similar primary provider - with copies of available medical evaluation and laboratory studies
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
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...
Time frame: 12/31/2028
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.
1 secondary outcome
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Oct 2026.
- Background: PubMed 16546624Sampson 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.
- Background: PubMed 16892779Webb 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.
- Background: PubMed 7717796Patterson 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.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: 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.
Related trials for Idiopathic Anaphylaxis
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pamela A Frischmeyer-Guerrerio, M.D. principal investigator
National Institute of Allergy and Infectious Diseases (NIAID)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Idiopathic Anaphylaxis and Drug Anaphylaxis, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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... (time frame: 12/31/2028). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00719719, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Oct 2026.