Mechanisms of Allergen Immunotherapy

NCT00001910 | Completed

• 2 other identifiers: 99014699-I-0146
• Study Type: observational
• Target: 50
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Asthma; Hypersensitivity

Keywords

T Cells; Allergy; Asthma; Cytokine; Vaccine

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• 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.
• 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.

You may not qualify if:

• 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
• 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.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

National Institute of Allergy and Infectious Diseases (NIAID)

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• 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.

  PMID: 8559203 BACKGROUND

• Bousquet 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.

  PMID: 9139771 BACKGROUND

• Bousquet 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.

  PMID: 9860031 BACKGROUND

MeSH Terms

Conditions

Asthma; Hypersensitivity

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Immune System Diseases

Study Design

• Study Type: observational
• Sponsor Type: NIH

Study Record Dates

• First Submitted: November 3, 1999
• First Posted: November 4, 1999
• Study Start: July 1, 1999
• Study Completion: August 1, 2003
• Last Updated: March 4, 2008

Record last verified: 2003-08

Locations

US (1)