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
- 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.
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.
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
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.
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.
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
Systemic Corticosteroids (other than physiologic replacement doses) within 3 months of
Beta-blockers (systemic or ophthalmic), doxepin, phenothiazines, tricyclic antidepressant,
or immunosuppressive (e.g., methotrexate) therapy within one month of study drug
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
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
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
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.