Clinical Response to Rhinovirus Challenge
Condition: Asthma; Allergic Rhinitis
MeSH terms: Rhinitis; Rhinitis, Allergic
Intervention: Rhinovirus (GMP RV16 HRV-16)
Intervention description: 300 tissue culture infectious dose (TCID)50 mg/ml intranasal one time only
Phase: Phase 2
Study type: Interventional
Primary purpose: Health Services Research
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 38.0
Sex: All
Minimum age: 18 Years
Maximum age: 40 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      Rhinovirus (RV) infections represent the most common cause of asthma exacerbations in
      children and adolescents. The investigators hypothesize that the immune responses generated
      in the nose of allergic rhinitics and asthmatics underlie subsequent systemic modulation of
      the immune system, and that - in susceptible individuals (i.e., those with pre-existing
      asthma) - this modified nasal milieu is responsible for the asthma exacerbation.

      Open label single center study in asthmatics as well as allergic rhinitis (AR) and healthy
      controls. All subjects will undergo good manufacturing practice (GMP) RV16 inoculation and
      responses will be compared between the 3 cohorts.
    

Eligibility criteria:

        Inclusion Criteria:

        All subjects:

          1. Subjects must be able to understand and provide written informed consent.

          2. Age 18 to ≤40 years of age, any gender, any racial/ethnic origin

          3. Female subjects of childbearing potential must have a negative pregnancy test upon
             study entry (day -7) and before each procedure involving pharmacologic interventions
             (days 0, 4, and 7).

          4. Female (and male) subjects with reproductive potential, must agree to use FDA approved
             methods of birth control for the duration of the study such as, but not limited to,
             birth control pills, contraceptive foam, diaphragm, IUD, abstinence, or condoms.

          5. Participants must be willing to comply with study procedures and requirements.

          6. Negative test for serum neutralizing antibody to RV16 at enrollment visit (<1:8)
             (Visit 1).

        Allergic Rhinitis Subjects:

          1. Allergy as determined by ≥1 positive prick skin test (wheal ≥5 mm diameter and 3mm
             larger than the diluent control) to Virginia inhalant panel within 5 years, and a
             history of symptoms of sneezing, rhinorrhea, pruritus, nasal congestion, and/or
             allergic conjunctivitis on natural exposure to relevant allergens.

          2. Negative methacholine challenge (less than 20% decline in functional expiratory volume
             in 1 second (FEV1) at ≤8mg/ml) within 1 year

          3. FEV1 ≥80% predicted, FEV1/FVC ≥80%.

          4. No history of wheezing with viral infection in the last 6 years, and no use of rescue
             inhalers or long-term controllers for asthma in the last 6 years.

        Allergic Asthmatic Subjects:

          1. Allergy as determined by ≥1 positive prick skin test (wheal ≥5 mm diameter and 3mm
             larger than the diluent control) to Virginia inhalant panel. Subjects are not required
             to have allergy symptoms at the time of study. Subjects will report history of
             symptoms of sneezing, rhinorrhea, pruritus, nasal congestion, and/or allergic
             conjunctivitis on natural exposure to relevant allergens.

          2. Asthma determined by physician diagnosis and by a positive methacholine challenge (at
             least 20% fall in FEV1 at a methacholine concentration of ≤8 mg/ml) at screening
             protocol visit before enrollment (obtained within the past year).

          3. Asthma must be controlled as determined by asthma control test (ACT) score ≥20 and
             normal lung function (FEV1>70% predicted or FEV1/FVC ratio >75% for subjects with FVC
             values between 80 and 87% predicted whose FEV1 values fall below 70%) at Visits 1 and
             2.

        Exclusion Criteria:

          1. Positive test for serum neutralizing antibody to RV16 at enrollment visit (≥1:8)
             (Visit 1).

          2. Upper airway modified Jackson criteria symptom scores ≥7 at time of inoculation.

          3. Chronic heart disease including bradycardia, lung diseases other than asthma, or other
             chronic illnesses including epilepsy, peptic ulcer disease, thyroid disease, urinary
             tract infection, vagotonia, autoimmune disease, primary or secondary immunodeficiency
             or any household contacts who are known to be immune deficient. Any medical conditions
             that could be adversely affected by the administration of cholinergic agent.

          4. Any use of corticosteroids, leukotriene (LT) modifiers, antihistamines, omalizumab,
             theophylline, long-acting anti-muscarinic antagonists (LAMAs), long-acting
             beta-agonists (LABAs), nedocromil, cromolyn use on a daily basis within 4 weeks prior
             to Visit 1.

          5. Current use of ß-blockers or cholinesterase inhibitors (for myasthenia gravis).

          6. ß2-agonist use ≥4 days/week in any week or ≥2 nights/month during the month before
             Visit 1.

          7. Recent (within 1-yr) asthma exacerbation requiring urgent care visit (unless the
             treatment involved only the use of a bronchodilator), hospitalization, or oral CCS

          8. Intubation or management in the intensive care unit (ICU) for an asthma exacerbation
             ever.

          9. An upper or lower respiratory tract infection within 2 months prior to enrollment.

         10. Previous nasal or sinus surgery within the last 12 months

         11. >5 pack-year smoking history or any smoking within the past 6 mos.

         12. Hemoglobin <11.5 g/dL for non-African American subjects or hemoglobin < 11.0 g/dL for
             African American subjects detected at Visit 1.

         13. Laboratory values (other than hemoglobin and absolute neutrophil count (ANC)) measured
             at Visit 1 that are considered to be of clinical relevance by the Investigator.

         14. Absolute neutrophil count (ANC) <1500 cells/mm3 (or 1.5 K/µL) or absolute lymphocyte
             count (ALC) <800 cells/mm3 detected at Visit 1.

         15. Use of investigational drugs within 12 weeks of participation

         16. Past or current medical problems or findings from physical examination or laboratory
             testing that are not listed above, which, in the opinion of the investigator, may pose
             additional risks from participation in the study, may interfere with the participant's
             ability to comply with study requirements or that may impact the quality or
             interpretation of the data obtained from the study.