Study Stopped
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Human Rhinovirus Infection and Airway Remodeling Mediators
Comparison of Airway Remodeling Mediators Following Experimental Human Rhinovirus Infection in Subjects With Mild to Moderate Asthma, and in Healthy, Non-asthmatic Control Subjects (AADCRC-UC-01)
2 other identifiers
interventional
2
1 country
1
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for not_applicable asthma
Started Apr 2013
Typical duration for not_applicable asthma
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
April 1, 2013
CompletedFirst Submitted
Initial submission to the registry
May 1, 2013
CompletedFirst Posted
Study publicly available on registry
May 7, 2013
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 1, 2015
CompletedStudy Completion
Last participant's last visit for all outcomes
July 1, 2015
CompletedAugust 14, 2015
August 1, 2015
2.2 years
May 1, 2013
August 12, 2015
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Bronchial Alveolar Lavage (BAL) Fluid Protein Levels
The primary endpoint will be the protein levels in BAL fluid at Day 4 (post-infection) minus the value at Day -7 (pre-infection) for each of MMP-9, VEGF amphiregulin and activin A.
Day -7 and Day 4
Secondary Outcomes (4)
Quantitative Changes in Gene Expression Between Groups
Day -7 and Day 4
Changes in symptom scores, viral titers, spirometry, airway responsiveness (PC20 methacholine) and FeNO levels.
Day -7 and Day 4
Quantification of inflammatory cells in the lower airways, assessed in BAL fluid and bronchial biopsies.
Day -7 and Day 4
Correlation of gene expression and protein levels of selected mediators with viral titer, symptom scores and numbers of inflammatory cells in the upper and lower airways.
Day -7 and Day 4
Study Arms (2)
Asthmatic Group
EXPERIMENTALSubjects with well-controlled, mild-moderate allergic asthma.Subjects will be inoculated with a total dose of 1000 TCID50 of HRV- 39. The inoculum is diluted, as appropriate, in lactated Ringer's solution and delivered via the following procedure: 0.5 ml per nostril is administered by pipette while the subject tilts their head back.
Healthy Non-Asthmatic Control Group
ACTIVE COMPARATORHealthy volunteers. Subjects will be inoculated with a total dose of 1000 TCID50 of HRV- 39. The inoculum is diluted, as appropriate, in lactated Ringer's solution and delivered via the following procedure: 0.5 ml per nostril is administered by pipette while the subject tilts their head back.
Interventions
Experimental rhinovirus infection: an FDA approved, GMP-grade HRV-39 stock (gift from Dr. Ronald B. Turner, University of Virginia), which has now been approved by Health Canada for human experimental use, will be used in this study.
The purpose of this test is to determine if lung airways narrow by more than 20%, which confirms an asthma diagnosis.
This process uses a rhinoprobe to gently scrape the mucosal lining of the nose
For the purposes of this study, allergy skin testing will be done with the following aero-allergens: cat epidermis, dog epidermis, horse, grass mix, tree mix, weed mix, ragweed and house dust mite, along with a histamine positive control and a buffer \& glycerol negative control.
Peripheral blood for assessment of neutralizing antibodies to HRV-39
A small flexible tube the size of a pencil, with a video-camera built into the tip (called a bronchoscope), will be inserted through the nose or mouth and down into the lungs.
Eligibility Criteria
You may qualify if:
- 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.
- +6 more criteria
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
University of Calgary
Calgary, Alberta, T2N 4Z6, Canada
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
David Proud, PhD
University of Calgary
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- BASIC SCIENCE
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 1, 2013
First Posted
May 7, 2013
Study Start
April 1, 2013
Primary Completion
July 1, 2015
Study Completion
July 1, 2015
Last Updated
August 14, 2015
Record last verified: 2015-08