Overview

Human Rhinovirus Infection and Airway Remodeling Mediators

Status:
Terminated
Trial end date:
2015-07-01
Target enrollment:
0
Participant gender:
All
Summary
In this study, the following subjects will be exposed to human rhinovirus (HRV): - those with classification of mild-moderate asthma - healthy control subjects. The investigators will study the kinetics of HRV-induced inflammatory and remodeling responses in a well characterized group of asthmatic subjects and compare these outcomes to those in a healthy, non-asthmatic control group.
Phase:
N/A
Accepts Healthy Volunteers?
Accepts Healthy Volunteers
Details
Lead Sponsor:
National Institute of Allergy and Infectious Diseases (NIAID)
Collaborator:
Asthma and Allergic Diseases Cooperative Research Centers
Treatments:
Methacholine Chloride
Polystyrene sulfonic acid
Criteria
Inclusion Criteria:

Asthmatics:

- Male or female volunteers with intermittent or persistent mild to moderate allergic
asthma, as defined by GINA guidelines 39.

- Between ≥18 and ≤ 50 years of age.

- Objective evidence of variable airflow limitation (≥12% and at least 200mL
post-bronchodilator reversibility from baseline), or airway hyperresponsiveness (PC20
methacholine <16mg/ml) at the screening visit or within past 24 months.

- Pre-bronchodilator spirometry at baseline; FEV1 ≥70% of predicted; FEV1/VC ≥50%.

- Atopic, as evidenced by positive skin prick tests to ≥1 common aero-allergen, where
positive is defined by a wheal of ≥2 mm compared to the negative control.

- Not be exposed to sensitizing seasonal allergens for at least 4 weeks before the
study. Chronic exposure to perennial allergens will be permitted.

- Asthma symptoms controlled by either inhaled β22-agonists alone, or by low or moderate
dose ICS (≤800mcg of budesonide or equivalent per day), administered either as
monotherapy or in a fixed-dose combination with a long-acting β22-agonist (LABA). The
doses of these maintenance medications should have remained stable for the 4 weeks
prior to the study screening phase (Visit 2).

- Stable asthma symptoms, with no history of asthma exacerbation requiring short burst
prednisone treatment within the 3 months prior to study entry.

- Be a non-smoker, as defined as no smoking in past 12 months, and have a lifetime ≤ 10
pack-year smoking history.

- In good general health (other than asthma) without clinically significant medical
history of other co-morbidities, and a BMI of ≤ 30 kg/m2.

- Have no history of any life threatening episode of asthma, as judged by the study
physician; this may include, but not be limited to, prior ICU admission or intubation.

- Subjects, or their partners, must be using a reliable form of contraception
continuously from 4 weeks prior, to 4 weeks post participation.

Non-Asthmatics:

- Male or female volunteers, ≥18 and ≤ 50 years of age, in good general health, without
a clinically significant medical history and a BMI of ≤ 30 kg/m2.

- Non-asthmatic, as defined by history and normal spirometry (FEV1 ≥80% and FEV1/FVC
≥75% of predicted value).

- Normal airway responsiveness (PC20 methacholine ≥16 mg/ml).

- Non-atopic, as determined by skin prick tests to common aero-allergens, where positive
test defined as a wheal of ≥ 2 mm compared to the negative control.

- Be a non-smoker for ≥1 year, and have a lifetime ≤ 10 pack-year smoking history of
smoking.

- Subjects, or their partners, must be using a reliable form of contraception
continuously from 4 weeks prior, to 4 weeks post participation.

- All potentially eligible study subjects must be willing to participate in study, and
be able to provide written consent prior to starting the study. The study protocol and
consent form will be approved by the Calgary Conjoint Health Research Ethics Board.

Exclusion Criteria:

- Presence of neutralizing antibodies to HRV-39 at the screening visit to a titer of ≥
1:2.

- Have symptoms of an active viral respiratory tract infection (cold symptoms),
corroborated by a score of 3 or higher on the Jackson cold symptom questionnaire,
during the screening phase (Visit 3).

- Current pregnancy or positive urine pregnancy test at screening or during the study.

- Use of any of the following medications in preceding 4 weeks prior to study entry and
during the study: : oral and topical antihistamines, leukotriene receptor antagonists,
inhaled anticholinergics, non-steroidal anti-inflammatory drugs (NSAIDS), antibiotics
and anti-viral medications, over the counter 'cold' and influenza remedies, including
decongestants, and oral anticoagulants.

- Use of prednisone within the last 3 months.

- Current acute or chronic illness (including infection) or recent recovery (within 4
weeks) from acute illness which could, in the opinion of the study physician, alter
inflammatory responses (e.g., influenza, cold or other respiratory infection, etc.). •
Autoimmune disease or immunodeficiency, or any household contacts who are known to be
immune deficient.

- Known allergy to lidocaine.

- Any other significant concomitant medical issue, or findings on physical examination
or laboratory testing that, in the opinion of the study physician, may pose additional
risks from participation in the study (including undergoing bronchoscopy), or which
may impact the quality or interpretation of the data obtained from the study.

- Clinically significant pre-bronchoscopy safety assessment laboratory tests (CBC, INR,
electrolytes and creatinine), as well as a positive urine pregnancy test on all female
subjects of child-bearing age, will be done at visit 2 (day -26) and visit 5 (Day 0)
prior to bronchoscopy on Day -7 and Day 4.