AsthmaNCT01847768
Human Rhinovirus Infection and Airway Remodeling Mediators
A study testing GMP-grade HRV-39, Bronchoalveolar Lavage and Methacholine Inhalation Challenge in people with Asthma, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in Canada.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Asthma
- What is being tested?
- GMP-grade HRV-39, Bronchoalveolar Lavage and Methacholine Inhalation Challenge
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 1 siteCanada
- Study dates
- Apr 2013to Jul 2015
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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)
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.
Read the detailed description
Although changes in the lungs, known as remodeling, are a feature of asthma, the causes and mechanisms involved in the process have not yet been found. Recently, it has been established that remodeling can be observed in children prior to a formal diagnosis of asthma. Clinical studies indicate that HRV, "common cold" infections, are a common cause of recurrent respiratory illnesses in childhood, and children with HRV-associated wheezing episodes have an increased risk of developing asthma. This led to the hypothesis that HRV infections may play a central role in the start of the airway remodeling leading to asthma.
The goal of this study is to determine if alterations in relevant airway remodeling growth factors differ between healthy controls and asthmatic subjects, pre- and post-HRV infection. These growth factors will be assessed in bronchoalveolar lavage (BAL) fluid and endobronchial biopsy tissues and correlated with viral levels in both nasal lavage and BAL fluid.
- Conditions
- Asthma
- Being tested
- GMP-grade HRV-39, Bronchoalveolar Lavage, Methacholine Inhalation Challenge, Nasal Lavage, Nasal Scrapings
- Keywords
- asthma, rhinovirus, remodeling mediators, human rhinovirus infection
- Medical subject headings
- Asthma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GMP-grade HRV-39Biological
Also called human rhinovirus, common cold
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.
Bronchoalveolar LavageProcedure or surgery
Methacholine Inhalation ChallengeDrug
The purpose of this test is to determine if lung airways narrow by more than 20%, which confirms an asthma diagnosis.
Nasal LavageProcedure or surgery
Nasal ScrapingsProcedure or surgery
This process uses a rhinoprobe to gently scrape the mucosal lining of the nose
Bronchial BrushingsProcedure or surgery
Lung Mucosal BiopsyProcedure or surgery
Allergen Skin Prick TestingProcedure or surgery
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.
VenipunctureProcedure or surgery
Also called Blood draw
Peripheral blood for assessment of neutralizing antibodies to HRV-39
BronchoscopyProcedure or surgery
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.
SpirometryProcedure or surgery
| Study group | Role | What they receive |
|---|---|---|
| Asthmatic Group | Experimental | Subjects 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. Receives: Biological: GMP-grade HRV-39; Procedure: Bronchoalveolar Lavage; Drug: Methacholine Inhalation Challenge; Procedure: Nasal Lavage; Procedure: Nasal Scrapings; Procedure: Bronchial Brushings; Procedure: Lung Mucosal Biopsy; Procedure: Allergen Skin Prick Testing; Procedure: Venipuncture; Procedure: Bronchoscopy; Procedure: Spirometry |
| Healthy Non-Asthmatic Control Group | Active comparator | Healthy 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. Receives: Biological: GMP-grade HRV-39; Procedure: Bronchoalveolar Lavage; Drug: Methacholine Inhalation Challenge; Procedure: Nasal Lavage; Procedure: Nasal Scrapings; Procedure: Bronchial Brushings; Procedure: Lung Mucosal Biopsy; Procedure: Allergen Skin Prick Testing; Procedure: Venipuncture; Procedure: Bronchoscopy; Procedure: Spirometry |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Day -7 and Day 4
Secondary outcomes (4)
Quantitative Changes in Gene Expression Between Groups
Quantitative changes in gene expression between groups in BAL fluid, bronchial brushings, nasal scrapings and mucosal biopsies, for selected airway remodeling mediator genes, including MMP-9, amphiregulin, VEGF and activin A.
Measured: Day -7 and Day 4
Changes in symptom scores, viral titers, spirometry, airway responsiveness (PC20 methacholine) and FeNO levels.
Measured: Day -7 and Day 4
Quantification of inflammatory cells in the lower airways, assessed in BAL fluid and bronchial biopsies.
Measured: 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.
Measured: Day -7 and Day 4
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 May 2013 (estimated)
- Study startApr 2013
- Primary completionJul 2015
- Study completionJul 2015
Why it stopped: Lack of Enrollment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for AsthmaStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Collaborators
- Asthma and Allergic Diseases Cooperative Research Centers
- Responsible party
- Sponsor
- Investigators
- David Proud, PhD, Principal investigator, University of Calgary
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01847768
- Sponsor's protocol ID
- DAIT AADCRC-UC-01
- Other IDs
- AADCRC-UC-01
- Status last verified
- Aug 2015
- First submitted
- 1 May 2013
- Last updated
- 14 Aug 2015
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Aug 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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)
- ClinicalTrials.gov ID
- NCT01847768
- Acronym / sponsor ID
- DAIT AADCRC-UC-01
- Conditions
- Asthma
- Keywords
- asthma, rhinovirus, remodeling mediators, human rhinovirus infection
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Lack of Enrollment
- Enrolment
- 2 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Collaborators
- Asthma and Allergic Diseases Cooperative Research Centers
- Study start
- Apr 2013
- Primary completion
- Jul 2015 (actual)
- Study completion
- Jul 2015 (actual)
- First posted
- 7 May 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Although changes in the lungs, known as remodeling, are a feature of asthma, the causes and mechanisms involved in the process have not yet been found. Recently, it has been established that remodeling can be observed in children prior to a formal diagnosis of asthma. Clinical studies indicate that HRV, "common cold" infections, are a common cause of recurrent respiratory illnesses in childhood, and children with HRV-associated wheezing episodes have an increased risk of developing asthma. This led to the hypothesis that HRV infections may play a central role in the start of the airway remodeling leading to asthma.
The goal of this study is to determine if alterations in relevant airway remodeling growth factors differ between healthy controls and asthmatic subjects, pre- and post-HRV infection. These growth factors will be assessed in bronchoalveolar lavage (BAL) fluid and endobronchial biopsy tissues and correlated with viral levels in both nasal lavage and BAL fluid.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Asthmatic Group | Experimental | Biological: GMP-grade HRV-39, Procedure: Bronchoalveolar Lavage, Drug: Methacholine Inhalation Challenge, Procedure: Nasal Lavage, Procedure: Nasal Scrapings, Procedure: Bronchial Brushings, Procedure: Lung Mucosal Biopsy, Procedure: Allergen Skin Prick Testing, Procedure: Venipuncture, Procedure: Bronchoscopy, Procedure: SpirometrySubjects 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 comparator | Biological: GMP-grade HRV-39, Procedure: Bronchoalveolar Lavage, Drug: Methacholine Inhalation Challenge, Procedure: Nasal Lavage, Procedure: Nasal Scrapings, Procedure: Bronchial Brushings, Procedure: Lung Mucosal Biopsy, Procedure: Allergen Skin Prick Testing, Procedure: Venipuncture, Procedure: Bronchoscopy, Procedure: SpirometryHealthy 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. |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (21 listed)
- 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.
Key exclusion criteria (9 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GMP-grade HRV-39Also: human rhinovirus, common coldExperimental 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. | Biological | Asthmatic Group, Healthy Non-Asthmatic Control Group |
| Bronchoalveolar Lavage | Procedure or surgery | Asthmatic Group, Healthy Non-Asthmatic Control Group |
| Methacholine Inhalation ChallengeThe purpose of this test is to determine if lung airways narrow by more than 20%, which confirms an asthma diagnosis. | Drug | Asthmatic Group, Healthy Non-Asthmatic Control Group |
| Nasal Lavage | Procedure or surgery | Asthmatic Group, Healthy Non-Asthmatic Control Group |
| Nasal ScrapingsThis process uses a rhinoprobe to gently scrape the mucosal lining of the nose | Procedure or surgery | Asthmatic Group, Healthy Non-Asthmatic Control Group |
| Bronchial Brushings | Procedure or surgery | Asthmatic Group, Healthy Non-Asthmatic Control Group |
| Lung Mucosal Biopsy | Procedure or surgery | Asthmatic Group, Healthy Non-Asthmatic Control Group |
| Allergen Skin Prick TestingFor 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. | Procedure or surgery | Asthmatic Group, Healthy Non-Asthmatic Control Group |
| VenipunctureAlso: Blood drawPeripheral blood for assessment of neutralizing antibodies to HRV-39 | Procedure or surgery | Asthmatic Group, Healthy Non-Asthmatic Control Group |
| BronchoscopyA 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. | Procedure or surgery | Asthmatic Group, Healthy Non-Asthmatic Control Group |
| Spirometry | Procedure or surgery | Asthmatic Group, Healthy Non-Asthmatic Control Group |
Primary outcome
Bronchial Alveolar Lavage (BAL) Fluid Protein Levels
Time frame: Day -7 and Day 4
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.
4 secondary outcomes
Quantitative Changes in Gene Expression Between Groups
Time frame: Day -7 and Day 4
Changes in symptom scores, viral titers, spirometry, airway responsiveness (PC20 methacholine) and FeNO levels.
Time frame: Day -7 and Day 4
Quantification of inflammatory cells in the lower airways, assessed in BAL fluid and bronchial biopsies.
Time frame: 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.
Time frame: Day -7 and Day 4
Results and safety
The study was stopped early (reason given: Lack of Enrollment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Aug 2015.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
David Proud, PhD principal investigator
University of Calgary
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing GMP-grade HRV-39, Bronchoalveolar Lavage and Methacholine Inhalation Challenge in people with Asthma, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 21 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 14 Aug 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was stopped early (reason given: Lack of Enrollment). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Bronchial Alveolar Lavage (BAL) Fluid Protein Levels (time frame: Day -7 and Day 4). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Aug 2015.