Common ColdPhase 1EHRVINCT01823640
Experimental Human Rhinovirus Infection
A Phase 1 study testing Human Rhinovirus strain 16 (HRV-16) in people with Common Cold, run by Radboud University Medical Center at 1 site in Netherlands.
Trial summary
Our primary objective is to set up the Human Rhinovirus (HRV)-model in our centre. In addition, to facilitate future clinical trials, we want to determine optimal read-out parameters and read-out time points for experimental HRV infection in healthy volunteers. Read more about this study
- Who is it for?
- Ages 18 to 35 yearsHealthy volunteers can take part
- Conditions the study is for
- Common Cold
- What is being tested?
- Human Rhinovirus strain 16 (HRV-16)
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 40 participants
- Where
- 1 siteNetherlands
- Study dates
- Mar 2013to Jun 2014
- Phase
- Phase 1
- 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 35 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Age ≥18 and ≤35 years of age
- Healthy
- Use of contraceptives (for female subjects only)
Who cannot join
- Pregnancy or lactating
- Pre-existent lung disease, including asthma
- A history of allergic rhinitis with positive allergen skin tests
- Use of any medication
- Use of alcohol > 5/day or >20/wk
- Use of any drugs
Show all 12Show fewer
- Current smoker or more than 5 pack-year history
- Frequently have nosebleeds
- Recent nasal or otologic surgery
- Febrile illness or a common cold within four weeks before the HRV challenge
- Currently participating in another clinical trial
- Use of antibiotics, norit, laxatives (up till 6 months prior to inclusion), cholestyramine, acid burn inhibitors or immune suppressive agents (up till 3 months prior to inclusion), and pre- and probiotics (up till 1 month prior to inclusion).
Trial locations and contacts
1 site in 1 country.
Netherlands1 site
Radboud University Nijmegen Medical Centre
Nijmegen, Gelderland, 6525 HB
About this study
Official title: Experimental Human Rhinovirus Infection, a Randomized Placebo-controlled Pilot Study
Our primary objective is to set up the Human Rhinovirus (HRV)-model in our centre. In addition, to facilitate future clinical trials, we want to determine optimal read-out parameters and read-out time points for experimental HRV infection in healthy volunteers. Furthermore, we want to analyze to what extent HRV can cause systemic immune effects, and we want to test if subjects with antibodies against HRV can be re-infected with the same virus, and if the presence of HRV antibodies influences the local clinical and immunological response upon infection. Additionally, to gain insight in the immune modulating properties of HRV, we want to investigate the immunological response to a HRV re-infection within one week to determine if there are mechanisms that provide immediate protection against re-infection. This facilitates a cross-over design of future pharmacological intervention-trials. Furthermore, we want to investigate the capacity of HRV infection to modulate the systemic immune response by analyzing the response of leukocytes ex vivo stimulated with different stimuli. Moreover, we want to evaluate the effects of HRV-16 infection on the host transcriptome and metabolome. Finally, The influence of HRV-16 infection on nasal and gut microbiota will be assessed.
Read the detailed description
The importance of the common cold derives primarily from its frequency and from its enormous socioeconomic impact. Human Rhinoviruses (HRVs) are the major cause of the common cold, being responsible for 30-50% of all acute respiratory illnesses with no causal remedies at hand. A model to investigate the pathophysiology of HRV infection and to test compounds that could treat or protect one from infection or developing symptoms would therefore be very valuable. With this HRV model it is also possible to investigate crosstalk between bacteria and viruses. This is very relevant because, following a viral infection, bacterial superinfections are common in clinical practice, and underlying mechanisms and subsequent possible therapies that could prevent this remain to be discovered. Worldwide, thousands of subjects have been exposed to experimental rhinovirus infection, of which more than 600 to HRV-16. Serious adverse events related to rhinovirus infection have never been documented. Therefore, this model can be considered a safe and highly reproducible model. Moreover, 52 volunteers have already been exposed to the HRV-16 virus from the batch that we want to use in this study.
Healthy volunteers who meet all inclusion criteria and none of the exclusion criteria that have given informed consent to participate in the study will be randomized to become either inoculated with HRV-16 (n=20; 10 male+10 female) or with placebo (saline 0.9%, n=20, 10 male+ 10 female). After one week a second inoculation with HRV-16 will be performed in both groups. In both groups, 50% of the subjects will be sero-negative and 50% sero-positive to HRV-16. One hundred TCID50 units of HRV-16 (by spraying 0.5 mL into each nostril in supine position in a randomized manner) will be administered.
The main study parameter is the rate of infection (defined by a positive viral culture, qPCR and/or a four-fold rise in antibody titre) caused by HRV-16 inoculation. Secondary endpoints include the duration of the incubation period, the effects of HRV-16 (re-)infection on cold symptoms and spirometry, kinetics of HRV-16-induced local inflammation parameters in nasal washes (including immune cells and cytokine production), kinetics of the HRV-16-induced systemic immune response (including circulating cytokines), the ability of HRV to modulate the systemic immune response (as reflected by the ex vivo production of inflammatory mediators by stimulated leukocytes), the effects of seropositivity on clinical and immunological responses, and the effects of HRV-16 infection on faecal and nasal-pharyngeal microbiota and host transcriptome and metabolome.
- Conditions
- Common Cold
- Being tested
- placebo, Human Rhinovirus strain 16 (HRV-16)
- Keywords
- HRV, Pharmacodynamics / kinetics, Resistance
- Medical subject headings
- Common Cold
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
placeboOther
Human Rhinovirus strain 16 (HRV-16)Other
100 TCID50 dosis of HRV-16 will be inoculated on day 7 and / or day 0
| Study group | Role | What they receive |
|---|---|---|
| Placebo-HRV | Experimental | inoculation with placebo followed by inoculation with HRV Receives: Other: placebo; Other: Human Rhinovirus strain 16 (HRV-16) |
| HRV-HRV | Experimental | inoculation with HRV followed by a second inoculation with HRV Receives: Other: Human Rhinovirus strain 16 (HRV-16) |
What is being measured
The primary outcome is the main question the study is designed to answer.
The main study parameter is the rate of infection (defined by a positive viral culture, qPCR and/or a four-fold rise in antibody titre) caused by HRV-16 inoculation.
Measured: up to day 28 (qPCR)
Secondary outcomes (9)
duration of the incubation period
Measured: inbetween day 0 (inoculation) and day 28
the effects of HRV-16 (re-)infection on cold symptoms and temperature
Measured: day 0 - day 28
the effects of HRV-16 (re-)infection on spirometry
Forced expiratory volume at a timed interval of 1 second (FEV1), and forced expiratory flow 25-75% (FEF 25-75%)
Measured: day 0 t/m day 4, day 7 t/m day 11. Day 14, 28
Leukocyte counts and differentiation (NK-cells, CD4 / CD8, neutrophils), and cytokine levels in nasal washes (including but not limited to IL-8, IL-1β, CCL5)
Measured: day 0 t/m day 4, day 7 t/m day 11. Day 14, 28
Leukocyte counts and circulating plasma cytokines (including but not limited to TNF-α, IL-6, IL-10, IFN-γ, IL-8, CCL5)
Measured: day 0 t/m day 4, day 7 t/m day 11. Day 14, 28
The cytokine response (including but not limited to TNF-α, IL-6, IL-10, IFN-γ), of leukocytes ex vivo stimulated with different stimuli (including but not limited to LPS, HRV, Staphylococcus aureus)
Measured: day 0 t/m day 4, day 7 t/m day 11. Day 14, 28
Composition of the gut microbiota
Measured: day 0, 2, 7, 9
The host transcriptome and metabolome
Measured: day 0, 2, 7, 9
Composition of the nasal-pharyngeal microbiota
Measured: day 0, 2, 7, 9
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Apr 2013 (estimated)
- Study startMar 2013
- Primary completionJun 2013
- Study completionJun 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Common ColdStudies of the same condition, open and under way.
- 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 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Radboud University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Peter Pickkers, MD, PhD, Study director, Radboud University Nijmegen Medical Centre, The Netherlands
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01823640
- Sponsor's protocol ID
- EHRVI
- Acronym
- EHRVI
- Status last verified
- Oct 2014
- First submitted
- 29 Mar 2013
- Last updated
- 15 Oct 2014
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 15 Oct 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Experimental Human Rhinovirus Infection, a Randomized Placebo-controlled Pilot Study
- ClinicalTrials.gov ID
- NCT01823640
- Acronym / sponsor ID
- EHRVI / EHRVI
- Conditions
- Common Cold
- Keywords
- HRV, Pharmacodynamics / kinetics, Resistance
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Radboud University Medical CenterUniversity, hospital or other
- Study start
- Mar 2013
- Primary completion
- Jun 2013 (actual)
- Study completion
- Jun 2014 (actual)
- First posted
- 4 Apr 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.
Our primary objective is to set up the Human Rhinovirus (HRV)-model in our centre. In addition, to facilitate future clinical trials, we want to determine optimal read-out parameters and read-out time points for experimental HRV infection in healthy volunteers. Furthermore, we want to analyze to what extent HRV can cause systemic immune effects, and we want to test if subjects with antibodies against HRV can be re-infected with the same virus, and if the presence of HRV antibodies influences the local clinical and immunological response upon infection. Additionally, to gain insight in the immune modulating properties of HRV, we want to investigate the immunological response to a HRV re-infection within one week to determine if there are mechanisms that provide immediate protection against re-infection. This facilitates a cross-over design of future pharmacological intervention-trials. Furthermore, we want to investigate the capacity of HRV infection to modulate the systemic immune response by analyzing the response of leukocytes ex vivo stimulated with different stimuli. Moreover, we want to evaluate the effects of HRV-16 infection on the host transcriptome and metabolome. Finally, The influence of HRV-16 infection on nasal and gut microbiota will be assessed.
Detailed description
The importance of the common cold derives primarily from its frequency and from its enormous socioeconomic impact. Human Rhinoviruses (HRVs) are the major cause of the common cold, being responsible for 30-50% of all acute respiratory illnesses with no causal remedies at hand. A model to investigate the pathophysiology of HRV infection and to test compounds that could treat or protect one from infection or developing symptoms would therefore be very valuable. With this HRV model it is also possible to investigate crosstalk between bacteria and viruses. This is very relevant because, following a viral infection, bacterial superinfections are common in clinical practice, and underlying mechanisms and subsequent possible therapies that could prevent this remain to be discovered. Worldwide, thousands of subjects have been exposed to experimental rhinovirus infection, of which more than 600 to HRV-16. Serious adverse events related to rhinovirus infection have never been documented. Therefore, this model can be considered a safe and highly reproducible model. Moreover, 52 volunteers have already been exposed to the HRV-16 virus from the batch that we want to use in this study.
Healthy volunteers who meet all inclusion criteria and none of the exclusion criteria that have given informed consent to participate in the study will be randomized to become either inoculated with HRV-16 (n=20; 10 male+10 female) or with placebo (saline 0.9%, n=20, 10 male+ 10 female). After one week a second inoculation with HRV-16 will be performed in both groups. In both groups, 50% of the subjects will be sero-negative and 50% sero-positive to HRV-16. One hundred TCID50 units of HRV-16 (by spraying 0.5 mL into each nostril in supine position in a randomized manner) will be administered.
The main study parameter is the rate of infection (defined by a positive viral culture, qPCR and/or a four-fold rise in antibody titre) caused by HRV-16 inoculation. Secondary endpoints include the duration of the incubation period, the effects of HRV-16 (re-)infection on cold symptoms and spirometry, kinetics of HRV-16-induced local inflammation parameters in nasal washes (including immune cells and cytokine production), kinetics of the HRV-16-induced systemic immune response (including circulating cytokines), the ability of HRV to modulate the systemic immune response (as reflected by the ex vivo production of inflammatory mediators by stimulated leukocytes), the effects of seropositivity on clinical and immunological responses, and the effects of HRV-16 infection on faecal and nasal-pharyngeal microbiota and host transcriptome and metabolome.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo-HRV | Experimental | Other: placebo, Other: Human Rhinovirus strain 16 (HRV-16)inoculation with placebo followed by inoculation with HRV |
| HRV-HRV | Experimental | Other: Human Rhinovirus strain 16 (HRV-16)inoculation with HRV followed by a second inoculation with HRV |
Who may qualify
- Ages
- 18 to 35 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- Age ≥18 and ≤35 years of age
- Healthy
- Use of contraceptives (for female subjects only)
Key exclusion criteria (12 listed)
- Pregnancy or lactating
- Pre-existent lung disease, including asthma
- A history of allergic rhinitis with positive allergen skin tests
- Use of any medication
- Use of alcohol > 5/day or >20/wk
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 |
|---|---|---|
| placebo | Other | Placebo-HRV |
| Human Rhinovirus strain 16 (HRV-16)100 TCID50 dosis of HRV-16 will be inoculated on day 7 and / or day 0 | Other | HRV-HRV, Placebo-HRV |
Primary outcome
The main study parameter is the rate of infection (defined by a positive viral culture, qPCR and/or a four-fold rise in antibody titre) caused by HRV-16 inoculation.
Time frame: up to day 28 (qPCR)
9 secondary outcomes
duration of the incubation period
Time frame: inbetween day 0 (inoculation) and day 28
the effects of HRV-16 (re-)infection on cold symptoms and temperature
Time frame: day 0 - day 28
the effects of HRV-16 (re-)infection on spirometry
Time frame: day 0 t/m day 4, day 7 t/m day 11. Day 14, 28
Leukocyte counts and differentiation (NK-cells, CD4 / CD8, neutrophils), and cytokine levels in nasal washes (including but not limited to IL-8, IL-1β, CCL5)
Time frame: day 0 t/m day 4, day 7 t/m day 11. Day 14, 28
Leukocyte counts and circulating plasma cytokines (including but not limited to TNF-α, IL-6, IL-10, IFN-γ, IL-8, CCL5)
Time frame: day 0 t/m day 4, day 7 t/m day 11. Day 14, 28
The cytokine response (including but not limited to TNF-α, IL-6, IL-10, IFN-γ), of leukocytes ex vivo stimulated with different stimuli (including but not limited to LPS, HRV, Staphylococcus aureus)
Time frame: day 0 t/m day 4, day 7 t/m day 11. Day 14, 28
Composition of the gut microbiota
Time frame: day 0, 2, 7, 9
The host transcriptome and metabolome
Time frame: day 0, 2, 7, 9
Composition of the nasal-pharyngeal microbiota
Time frame: day 0, 2, 7, 9
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Oct 2014.
Related trials for Common Cold
Not yet recruitingObservational study
Post-market Clinical Follow-up Study of an Isotonic Saline Solution for the Relief of Nasal Congestion in Infants and Toddlers
Nasal Congestion, Common Cold
Recruiting
Effect of Immune X on Common Cold Incidence in Healthy Adults
Common Cold, Upper Respiratory Tract Infection (URTI)
Not yet recruiting
Enhanced Telemedicine in Primary Care for Acute Respiratory Tract Infections Study
Acute Respiratory Tract Infection, Ear Infection
Recruiting
Omega-Cold Supplementation With Free Fatty Acids for the Prevention of Respiratory Infections in Adults.
Respiratory Infections
Recruiting
Safety and Performance Assessment of the Decongestant Seawater Spray Pocket Valve Enriched With Essential Oils in Patients With Acute Rhinitis Associated With Nasal Obstruction: "DEVALPO"
Acute Rhinitis, Nasal Obstruction
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.
Peter Pickkers, MD, PhD study director
Radboud University Nijmegen Medical Centre, The Netherlands
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Human Rhinovirus strain 16 (HRV-16) in people with Common Cold, run by Radboud University Medical Center at 1 site in Netherlands.
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 3 inclusion and 12 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: finished, as of the sponsor's last update on 15 Oct 2014. 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 Netherlands. 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.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
The main study parameter is the rate of infection (defined by a positive viral culture, qPCR and/or a four-fold rise in antibody titre) caused by HRV-16 inoculation. (time frame: up to day 28 (qPCR)). 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 15 Oct 2014; AzTrials last refreshed its copy on 27 Oct 2026.