AsthmaNCT00001910
Mechanisms of Allergen Immunotherapy
An observational study of Asthma and Hypersensitivity, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
Trial summary
This study will examine how allergen immunotherapy (allergy shots) works to reduce or prevent reactions to allergens such as pollen, dust or cat dander. Certain T cells (types of white blood cells) called Th2 cells produce substances that generate allergies. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Asthma, Hypersensitivity
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 1999to Aug 2003
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Age 18-50 years.
- History of asthma for one year or greater.
- Asthma symptoms (wheezing, chest tightness, shortness of breath) on exposure to allergen (by history or challenge).
- 10-20 mm erythema and/or 5 mm wheal response to one or more panel allergens via prick testing.
- Screening forced expiratory volume (FEV(1)) or the ratio of FEV(1) to forced vial capacity (FEV(1)/FVC) must be equal to or greater than 70% of the predicted value for age and sex.
- Frequency of IL-4 producing allergen specific CD4 T cells must be greater than or equal to 0.01% at time of screening.
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- Baseline values within the following laboratory ranges:
- White blood cell count greater than or equal to 3,300 and less than 10,500 cells/L;
- Absolute neutrophil count greater than or equal to 1,500 cells/microliter;
- Hemoglobin greater than or equal to 12 g/dL;
- Platelet count greater than or equal to 100,000/microliter;
- Serum creatinine less than 1.7 mg/dL;
- Total bilirubin less than 1.5 mg/dL;
- AST, ALT less than 50 U/L;
- Urinalysis within normal limits.
- Written informed consent
- Women of childbearing potential must agree to use adequate contraception (diaphragm with spermicide, condom with spermicide, intrauterine device (IUD), birth control pills or Norplant) for the duration of the study.
Who cannot join
- Asthma that requires more than twice weekly administration of short acting inhaled Beta-agonist bronchodilator. Long acting Beta-agonists such as Salmeterol may be used twice daily.
- Systemic Corticosteroids (other than physiologic replacement doses) within 3 months of study
- Beta-blockers (systemic or ophthalmic), doxepin, phenothiazines, tricyclic antidepressant, or immunosuppressive (e.g., methotrexate) therapy within one month of study drug administration
- System H1 antihistamine use within 1 week of baseline allergen skin testing
- Use of any investigational drug within 1 month of study
- History of angina or cardiac arrhythmias requiring drug or devices intervention
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- Clinically significant electrocardiographic (ECG) abnormalities
- Pregnancy or nursing (at screening or during course of study)
- Anaphylaxis with hypotension after allergen exposure in the past 10 years
- Systemic allergic desensitization therapy within two (2) years prior to study entry
- Rheumatologic or autoimmune disease requiring greater than 1 month of drug therapy in the last 5 years
- Diabetes
- HIV seropositivity
- Screening BP greater than 90 mm Hg diastolic or 160 mm Hg systolic
- Any other major illness or condition that, in the opinion of the principal investigator, may interfere with the patient's ability to comply with the conditions or substantially increase the risk associated with the patient's participation in this study.
- Upper respiratory infection affecting the subject's asthma in the 2 weeks prior to study drug.
- Increase in asthma symptoms of more than 2 additional episodes per week in the 2 weeks prior to study drug.
- Consistent alcohol use of more than 2 drinks a day in the past 6 months. 1 drink = 8 oz. Wine, 16 oz. beer, 2 oz. liquor.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institute of Allergy and Infectious Diseases (NIAID)
Bethesda, Maryland, 20892
About this study
Official title: Immunologic Mechanism of Allergen Immunotherapy
This study will examine how allergen immunotherapy (allergy shots) works to reduce or prevent reactions to allergens such as pollen, dust or cat dander. Certain T cells (types of white blood cells) called Th2 cells produce substances that generate allergies. Other T cells called Th1 cells produce substances that have opposite effects. This study will determine if allergy shots change the immune response to allergens by reducing the number of Th2 cells or by changing them into Th1 cells. A better understanding of how this treatment works may help scientists develop more effective allergy therapies.
People between 18 and 50 years of age who have had allergic asthma for at least 1 year may participate in this study. Candidates' medical, allergy and medication histories will be reviewed, and they will have a physical examination, including routine blood tests, urinalysis, electrocardiogram (EKG), and lung function test. Blood will also be drawn to test T cell response to allergens, and 12 skin tests (similar to a tuberculosis skin test) will be done to test for sensitivity to various allergens.
Read more
Participants will be admitted to the Clinical Center for 1 to 2 days for rush therapy (see below). They will have a brief history and physical examination. A heparin lock (thin plastic tube similar to an intravenous line) will be placed in an arm vein. They will then undergo the following procedures:
- Rush/Cluster Immunotherapy - An allergen is given in increasing doses over 2 to 5 weeks. During rush therapy, the dose is increased rapidly over 1 to 2 days until a moderate level dose is reached. To reduce the chance of an allergic reaction, patients take prednisone, cetirizine (Zyrtec® (Registered Trademark)), ranitidine (Zantac® (Registered Trademark)) and montelukast (Singular® (Registered Trademark)) starting 24 hours before treatment begins until rush therapy ends. After discharge on the third day, patients return to the clinic once a week for the next 2 to 5 weeks for cluster therapy, in which the dose is increased more gradually to a maintenance level.
- Maintenance Immunotherapy - Participants receive 12 weekly injections at the maintenance dose. Blood is drawn during one visit between weeks 2 and 7 of maintenance therapy.
- Follow-up Visits - Patients return to the clinic 2 and 3 weeks after the last maintenance dose for blood draws and evaluations. In addition, a "late-phase" allergen skin test is done at the 3-week follow-up to compare reaction results with those from the test done at the screening visit.
- End-of-Study Visit - 12 to 16 weeks after the last allergy shot, patients return for a final blood draw and brief evaluation.
Read the detailed description
Asthma is a major public health problem due to its high prevalence and significant impact on activities of daily living. Allergen immunotherapy or vaccination consists of the therapeutic administration of allergen extract. The efficacy of allergen immunotherapy in asthma is modest, however immunotherapy remains the only known disease modifying therapy for allergic asthma. Because the exact mechanism through which immunotherapy works is unclear, a greater understanding of the mechanism of action of allergen immunotherapy is needed before modern immunopharmacologic methods can be applied to increase its therapeutic efficacy. This goal of the study is to determine the effects of allergen immunotherapy on allergen specific T cell responses. This is an open label study in which allergen specific CD4+T lymphocyte responses will be monitored before, during and after 12 weekly injections of maintenance immunotherapy, allowing the study of both the induction as well as decay of these changes. Immunotherapy will be employed in a rush/cluster schedule consisting of the serial administration of rapidly increasing doses of allergen delivered subcutaneously over a 2 day period (rush), followed by more gradually increasing weekly injections over 2-6 weeks (cluster), during which time the subject is brought to a maintenance allergen dose, which will then be repeatedly administered on a weekly basis. Immunological endpoints will consist of the frequency and cytokine profile of allergen specific T cell responses as measured by intracellular cytokine staining and the measurement of in vitro induced T cell cytokines by real time RT-PCR. Ten allergic asthmatic subjects will be enrolled in the therapeutic arm of the study.
- Conditions
- Asthma, Hypersensitivity
- Keywords
- T Cells, Allergy, Asthma, Cytokine, Vaccine
- Medical subject headings
- Asthma, Hypersensitivity
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Nov 1999 (estimated)
- Study startJul 1999
- Study completionAug 2003
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 AsthmaStudies 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
- Enrolment
- 50 participants
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00001910
- Sponsor's protocol ID
- 990146
- Other IDs
- 99-I-0146
- Status last verified
- Aug 2003
- First submitted
- 3 Nov 1999
- Last updated
- 4 Mar 2008
- Results posted
- No
Publications
Creticos PS, Reed CE, Norman PS, Khoury J, Adkinson NF Jr, Buncher CR, Busse WW, Bush RK, Gadde J, Li JT, et al. Ragweed immunotherapy in adult asthma. N Engl J Med. 1996 Feb 22;334(8):501-6. doi: 10.1056/NEJM199602223340804.
PubMed 8559203Bousquet J, Yssel H, Vignola AM, Chanez P. New developments in the immunology of asthma, with a focus on mechanisms and treatment. Curr Opin Pulm Med. 1997 Jan;3(1):42-50. doi: 10.1097/00063198-199701000-00007.
PubMed 9139771Bousquet J, Lockey R, Malling HJ, Alvarez-Cuesta E, Canonica GW, Chapman MD, Creticos PJ, Dayer JM, Durham SR, Demoly P, Goldstein RJ, Ishikawa T, Ito K, Kraft D, Lambert PH, Lowenstein H, Muller U, Norman PS, Reisman RE, Valenta R, Valovirta E, Yssel H. Allergen immunotherapy: therapeutic vaccines for allergic diseases. World Health Organization. American academy of Allergy, Asthma and Immunology. Ann Allergy Asthma Immunol. 1998 Nov;81(5):401-5. doi: 10.1016/s1081-1206(10)63136-5. No abstract available.
PubMed 9860031
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Immunologic Mechanism of Allergen Immunotherapy
- ClinicalTrials.gov ID
- NCT00001910
- Acronym / sponsor ID
- 990146
- Conditions
- Asthma, Hypersensitivity
- Keywords
- T Cells, Allergy, Asthma, Cytokine, Vaccine
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 50 participants
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- Jul 1999
- Study completion
- Aug 2003
- First posted
- 4 Nov 1999 (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 examine how allergen immunotherapy (allergy shots) works to reduce or prevent reactions to allergens such as pollen, dust or cat dander. Certain T cells (types of white blood cells) called Th2 cells produce substances that generate allergies. Other T cells called Th1 cells produce substances that have opposite effects. This study will determine if allergy shots change the immune response to allergens by reducing the number of Th2 cells or by changing them into Th1 cells. A better understanding of how this treatment works may help scientists develop more effective allergy therapies.
People between 18 and 50 years of age who have had allergic asthma for at least 1 year may participate in this study. Candidates' medical, allergy and medication histories will be reviewed, and they will have a physical examination, including routine blood tests, urinalysis, electrocardiogram (EKG), and lung function test. Blood will also be drawn to test T cell response to allergens, and 12 skin tests (similar to a tuberculosis skin test) will be done to test for sensitivity to various allergens.
Participants will be admitted to the Clinical Center for 1 to 2 days for rush therapy (see below). They will have a brief history and physical examination. A heparin lock (thin plastic tube similar to an intravenous line) will be placed in an arm vein. They will then undergo the following procedures:
- Rush/Cluster Immunotherapy - An allergen is given in increasing doses over 2 to 5 weeks. During rush therapy, the dose is increased rapidly over 1 to 2 days until a moderate level dose is reached. To reduce the chance of an allergic reaction, patients take prednisone, cetirizine (Zyrtec® (Registered Trademark)), ranitidine (Zantac® (Registered Trademark)) and montelukast (Singular® (Registered Trademark)) starting 24 hours before treatment begins until rush therapy ends. After discharge on the third day, patients return to the clinic once a week for the next 2 to 5 weeks for cluster therapy, in which the dose is increased more gradually to a maintenance level.
- Maintenance Immunotherapy - Participants receive 12 weekly injections at the maintenance dose. Blood is drawn during one visit between weeks 2 and 7 of maintenance therapy.
- Follow-up Visits - Patients return to the clinic 2 and 3 weeks after the last maintenance dose for blood draws and evaluations. In addition, a "late-phase" allergen skin test is done at the 3-week follow-up to compare reaction results with those from the test done at the screening visit.
- End-of-Study Visit - 12 to 16 weeks after the last allergy shot, patients return for a final blood draw and brief evaluation.
Detailed description
Asthma is a major public health problem due to its high prevalence and significant impact on activities of daily living. Allergen immunotherapy or vaccination consists of the therapeutic administration of allergen extract. The efficacy of allergen immunotherapy in asthma is modest, however immunotherapy remains the only known disease modifying therapy for allergic asthma. Because the exact mechanism through which immunotherapy works is unclear, a greater understanding of the mechanism of action of allergen immunotherapy is needed before modern immunopharmacologic methods can be applied to increase its therapeutic efficacy. This goal of the study is to determine the effects of allergen immunotherapy on allergen specific T cell responses. This is an open label study in which allergen specific CD4+T lymphocyte responses will be monitored before, during and after 12 weekly injections of maintenance immunotherapy, allowing the study of both the induction as well as decay of these changes. Immunotherapy will be employed in a rush/cluster schedule consisting of the serial administration of rapidly increasing doses of allergen delivered subcutaneously over a 2 day period (rush), followed by more gradually increasing weekly injections over 2-6 weeks (cluster), during which time the subject is brought to a maintenance allergen dose, which will then be repeatedly administered on a weekly basis. Immunological endpoints will consist of the frequency and cytokine profile of allergen specific T cell responses as measured by intracellular cytokine staining and the measurement of in vitro induced T cell cytokines by real time RT-PCR. Ten allergic asthmatic subjects will be enrolled in the therapeutic arm of the study.
Study design
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (17 listed)
- Age 18-50 years.
- History of asthma for one year or greater.
- Asthma symptoms (wheezing, chest tightness, shortness of breath) on exposure to allergen (by history or challenge).
- 10-20 mm erythema and/or 5 mm wheal response to one or more panel allergens via prick testing.
- Screening forced expiratory volume (FEV(1)) or the ratio of FEV(1) to forced vial capacity (FEV(1)/FVC) must be equal to or greater than 70% of the predicted value for age and sex.
Key exclusion criteria (18 listed)
- Asthma that requires more than twice weekly administration of short acting inhaled Beta-agonist bronchodilator. Long acting Beta-agonists such as Salmeterol may be used twice daily.
- Systemic Corticosteroids (other than physiologic replacement doses) within 3 months of study
- Beta-blockers (systemic or ophthalmic), doxepin, phenothiazines, tricyclic antidepressant, or immunosuppressive (e.g., methotrexate) therapy within one month of study drug administration
- System H1 antihistamine use within 1 week of baseline allergen skin testing
- Use of any investigational drug within 1 month of study
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
Not reported in the source record.
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 4 Mar 2008.
- Background: PubMed 8559203Creticos PS, Reed CE, Norman PS, Khoury J, Adkinson NF Jr, Buncher CR, Busse WW, Bush RK, Gadde J, Li JT, et al. Ragweed immunotherapy in adult asthma. N Engl J Med. 1996 Feb 22;334(8):501-6. doi: 10.1056/NEJM199602223340804.
- Background: PubMed 9139771Bousquet J, Yssel H, Vignola AM, Chanez P. New developments in the immunology of asthma, with a focus on mechanisms and treatment. Curr Opin Pulm Med. 1997 Jan;3(1):42-50. doi: 10.1097/00063198-199701000-00007.
- Background: PubMed 9860031Bousquet J, Lockey R, Malling HJ, Alvarez-Cuesta E, Canonica GW, Chapman MD, Creticos PJ, Dayer JM, Durham SR, Demoly P, Goldstein RJ, Ishikawa T, Ito K, Kraft D, Lambert PH, Lowenstein H, Muller U, Norman PS, Reisman RE, Valenta R, Valovirta E, Yssel H. Allergen immunotherapy: therapeutic vaccines for allergic diseases. World Health Organization. American academy of Allergy, Asthma and Immunology. Ann Allergy Asthma Immunol. 1998 Nov;81(5):401-5. doi: 10.1016/s1081-1206(10)63136-5. No abstract available.
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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.
The record lists no contact. Use the official record to reach the sponsor.
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 Asthma and Hypersensitivity, 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 17 inclusion and 18 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 4 Mar 2008. 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.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00001910, 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 4 Mar 2008.