HealthyNCT02284074
Nasal LPS Challenge in Healthy Volunteers
A study testing Nasal LPS spray, Experimental: Nasal LPS spray 1µg and Experimental: Nasal LPS spray 10 µg in people with Healthy, run by Imperial College London at 1 site in United Kingdom.
Trial summary
The purpose of this study is to develop a nasal challenge model that causes a mild degree of inflammation, without causing any pain or symptoms, but that allows us to measure a variety of proteins in nasal secretions which causes inflammation in the nose. Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- Nasal LPS spray, Experimental: Nasal LPS spray 1µg and Experimental: Nasal LPS spray 10 µg
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Oct 2010to Apr 2011
- 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 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Males and females aged 18 to 60 years
- Current non-smokers for last 6 months (<5 cigs per week), with a smoking history of <5 pack years
- BMI 20-30 kg/m2
Who cannot join
- History of allergy
- Upper airway infection in 2 weeks before screening
- Lower respiratory tract infection in past 3 months
- Treatment with local or systemic corticosteroids during previous 2 months
- Signs or symptoms of chronic rhinitis, hypertrophy of turbinates, major septum deviation, nasal polyposis or recurrent sinusitis
- Previous nasal or sinus surgery
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- Clinically significant cardiovascular, hepatic, GIT, renal, endocrine, infective, haematological, neurological, dermatological, neoplastic conditions, gastro-oesophageal reflux, depression, TB
- Participation in a therapeutic drug trial in the prior 30 days.
- Medical therapy other than that permitted for contraception.
- Positive pregnancy test
- Inability or unwillingness to use contraception if the patient is a female of child-bearing age.
- History of drug abuse or urine test showing evidence of recreational drug abuse
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Imperial Clinical Respiratory Research Unit (ICRRU), St Mary's Hospital
Paddington, London, W2 1NY
About this study
Official title: Nasal Lipopolysaccharide (LPS) Challenge in Healthy Volunteers (HVs): Investigation of Tolerability, Dose Response and the Expression Profile of Intercellular Adhesion Molecule-1 (ICAM-1)
The purpose of this study is to develop a nasal challenge model that causes a mild degree of inflammation, without causing any pain or symptoms, but that allows us to measure a variety of proteins in nasal secretions which causes inflammation in the nose. The nasal challenge model involves spraying the nostrils in the form of a fine mist with 4 different doses (1, 10, 30 and 100µg per nostril) of lipopolysaccharide (LPS) including a placebo. LPS is a type of protein which has been carefully purified from the outer cell wall of certain bacteria, is sterile and does not contain live bacteria, and will not cause infection.
The investigators will measure any inflammation in the nose by looking at cells collected by washing the inside of the nose (nasal lavage) and placing small strips of paper in the nasal cavity. The paper absorbs the nasal fluid and the chemicals produced during inflammation and can be extracted from the paper and analysed in the laboratory. The investigators will also be collecting a small amount of nasal epithelium taken by way of a nasal scrape; this is done by using a Rhinoprobe, a small plastic curette which is used to scrape a small piece of lining of the nose. The investigators hope that information obtained from this study will be used in future studies that will test new study drugs designed to treat diseases of the airways and lungs ( like asthma and chronic obstructive pulmonary disease (COPD) and hay fever.
Read the detailed description
STUDY DESIGN AND METHODOLOGY This is a single-centre study which will be carried out at the Imperial Clinical Respiratory Research Unit (ICRRU) at St Mary's Hospital in London Paddington.
RECRUITMENT The study will recruit a total of 15 healthy participants.
STUDY VISITS The study will involve a total of 11 outpatients visits. The screening visit is the initial visit where the study is discussed with the participant and written informed consent is obtained by the PI or his designee. This is done prior to performing any study related procedures. The participant will have had the study information sheet for at least 24 hours prior to the visit.
The visit will include the collection of demographic data, height and weight, physical examination by a doctor, medical history, vital signs, body temperature, 12 lead ECG, laboratory assessments (safety bloods) urine drugs of abuse test and pregnancy tests for females. The participant will also be asked to indicate the presence of any nasal symptoms by completing a modified total nasal symptoms score sheet and perform a peak nasal inspiratory flow (PNIF) test.
If eligible, participants will be asked to return for further study visits. Participants will be given 4 different doses of LPS and a placebo in a randomised manner.
There are a total of 5 treatment periods. Each treatment period consists of a 11h visit the first day and a 20 minute visit the following day. There is a total of 12-28 days interval between each treatment period visit.
During the treatment period visits, the study participants will undergo the following study procedures:
- Nasal lavage to both nostrils and discard with 5ml of 0.9% saline in order to clean the nose prior to nasal LPS challenge.
- Nasal challenge with LPS (placebo, 1,10, 30 or 100µg per nostril)
- Nasosorption (right nostril) at -30m, +30m, +1h, then hourly to 10h and 24h
- Nasal lavage (left nostril) at -30m, +2h, +4h, +8h, +24h
- Nasal scrape (left nostril) at -30m, +3h, +6h, +24h
- Modified total nasal symptom score (TNSS) at -30m, +30m, +1h, then hourly to 10h and 24h
- Peak nasal inspiratory flow (PNIF) rate at -30m, +2h, +4h, +8h, 24h
- Systemic adverse events
- Temperature (oral) at -30m, +2h, +4h, +8h
- Blood pressure and heart rate at -30m
- Females of child bearing potential will have a pregnancy test performed.
NASAL PROCEDURES IN THE STUDY
- Nasal washing (nasal lavage): Nasal washings in the nose are carried out by passing a small volume of salt water (saline) fluid into the nose. A nasal adapter shaped like an olive is placed inside the nostril. The participant is then asked to sit forward and the salty water solution (saline) is used to flush in and out of the nose over a one minute period. This procedure is carried out on both nostrils to clean up the nose on the initial study visit and then repeated only on the left nostril on each treatment visit.
- Nasal lining fluid absorption (nasosorption or SAM): A small strip of absorbent material, that looks and feels like soft tissue paper, will be used to absorb moisture from the inside surface of the nostril. The special absorptive paper will be placed inside the nostril and left for a period of 2 minutes to absorb the nasal lining fluid before being removed, gently sucking up fluid like blotting paper. Putting the paper into the nose can tickle, and cause your eyes to water a little. However, the nasosorption does not hurt and the investigators method has proved to be well tolerated in babies, children and adults. The paper absorbs the nasal fluid and many substances produced by the nasal cells can then be extracted from the paper and measured in the laboratory.
- Nasal scrape (nasal curettage or Rhinoprobe): A small sterile disposable plastic probe will be inserted into the nose and will be gently pressed against the inside surface lining of the nostril. The 3 inch long probe has a tiny scoop on the end, which can barely be see. 24 tiny samples from each nostril (a pinhead, 2mm, of tissue) will be taken from a part of the nose that has a reduced nerve supply to limit any discomfort. Taking this sample does not cause bleeding, but may cause some mild discomfort, and may make the eyes water slightly. The probe will collect nasal cells from the surface of the nostril which will then be sent for analysis. This method has been performed on many adults, children, and babies, and has been very well tolerated.
STATISTICAL ANALYSIS Each of the measures will be summarised descriptively by dose and time using appropriate summary statistics. If appropriate, response variables will be transformed (e.g. log-transformed). Gene expression data will be normalised by house-keeper gene. The TNSS will be calculated by summing the scores of nasal blockage, nasal discharge/rhinorrhoea, nasal burning/itching/pain sensation, and sneezing at each timepoint. Weighted means of symptom scores will be calculated over the time interval 0 to 10h.
TNSS, nasal sniff pressures, nasosorption measures and gene expression data from the nasal scrapes will each be plotted against time, with a separate plot for each subject and measure, and with LPS dose and placebo represented by separate lines on the plots. Summary statistics (e.g. mean +/- 95% confidence intervals or median and interquartile range) for nasal lavage and gene expression data will be plotted by dose against time.
Correlations will be explored using scatter plots for the following measures:
- Weighted means TNSS vs. maximum TNF-α
- Weighted means TNSS vs. maximum IL-8
- Weighted means TNSS vs. maximum s-ICAM-1
- Maximum ICAM-1 expression vs. maximum TNF-α
Reproducibility of the nasal LPS challenge for ICAM-1 expression and TNF-α will be explored using the following subsets of data:
- Predose data for each period to explore intra-subject variability. Parameter vs. period number will be plotted with a separate line for each subject to explore whether there is a period effect. Box and whisker plots will also be used to summarise the parameter by period.
- Placebo period data - Parameter vs time will be plotted with a separate line for each subject to explore whether there is a time-course effect. Box and whisker plots will also be used to summarise the parameter over time.
Box and whisker plots for ICAM-1 expression and TNF-α and dose and time will be presented to investigate whether these measures return to baseline after 24h.
Additional exploratory analyses may be performed to further characterize the expression profile of ICAM following nasal LPS challenge.
- Conditions
- Healthy
- Being tested
- Nasal LPS spray, Experimental: Nasal LPS spray 1µg, Experimental: Nasal LPS spray 10 µg, Experimental: Nasal LPS spray 30 µg, Experimental: Nasal LPS spray 100 µg
- Keywords
- Lipopolysaccharide (LPS), Biomarkers, Chemokines, Cytokines, Gene Expression, Nasal Challenge, Inflammation, Nasal, Nasosorption, Respiratory
- Medical subject headings
- Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nasal LPS sprayOther
LPS solution (250µl) will be prepared at 10, 100, 300 and 1000µg/ml, 100µl is administered to each nostril, both nostrils will be sprayed. The dose per nostril corresponds to 1, 10, 30 and 100µg.
Experimental: Nasal LPS spray 1µgOther
LPS solution (250µl) will be prepared at 10, 100, 300 and 1000µg/ml, 100µl is administered to each nostril, both nostrils will be sprayed.
Experimental: Nasal LPS spray 10 µgOther
LPS solution (250µl) will be prepared at 10, 100, 300 and 1000µg/ml, 100µl is administered to each nostril, both nostrils will be sprayed.
Experimental: Nasal LPS spray 30 µgOther
LPS solution (250µl) will be prepared at 10, 100, 300 and 1000µg/ml, 100µl is administered to each nostril, both nostrils will be sprayed.
Experimental: Nasal LPS spray 100 µgOther
LPS solution (250µl) will be prepared at 10, 100, 300 and 1000µg/ml, 100µl is administered to each nostril, both nostrils will be sprayed.
| Study group | Role | What they receive |
|---|---|---|
| Nasal LPS spray - placebo | Experimental | This is a 5-way crossover, randomised, placebo-controlled study.
Arms consists of the following nasal challenges:
placebo, 1, 10, 30 and 100µg LPS. Receives: Other: Nasal LPS spray |
| Nasal LPS spray 1µg | Experimental | This is a 5-way crossover, randomised, placebo-controlled study.
Arms consists of the following nasal challenges:
placebo, 1, 10, 30 and 100µg LPS. Receives: Other: Experimental: Nasal LPS spray 1µg |
| Nasal LPS spray 10 µg | Experimental | This is a 5-way crossover, randomised, placebo-controlled study.
Arms consists of the following nasal challenges:
placebo, 1, 10, 30 and 100µg LPS. Receives: Other: Experimental: Nasal LPS spray 10 µg |
| Nasal LPS spray 30 µg | Experimental | This is a 5-way crossover, randomised, placebo-controlled study.
Arms consists of the following nasal challenges:
placebo, 1, 10, 30 and 100µg LPS. Receives: Other: Experimental: Nasal LPS spray 30 µg |
| Nasal LPS spray 100 µg | Experimental | This is a 5-way crossover, randomised, placebo-controlled study.
Arms consists of the following nasal challenges:
placebo, 1, 10, 30 and 100µg LPS. Receives: Other: Experimental: Nasal LPS spray 100 µg |
What is being measured
The primary outcome is the main question the study is designed to answer.
Level of nasal mucosal inter-cellular adhesion molecule-1 (ICAM-1) by gene expression analysis
Measurement of gene expression (mRNA) for inter-cellular adhesion molecule-1 (ICAM-1) in nasal mucosal curettage samples, 8h following nasal lipopolysaccharide (LPS) challenge.
Measured: 8 hours following nasal lipopolysaccharide (LPS) challenge
Secondary outcomes (3)
Nasal mucosal lining fluid IL-1beta levels after nasal lipopolysaccharide (LPS) challenge
Nasal mucosal IL-1beta levels after LPS challenge (area under curve, 0 to 8h) will be compared to placebo responses (AUC, 0-8h) in nasal mucosal lining fluid
Measured: Up to 8h after nasal LPS challenge
Nasal mucosal lining fluid IL-6 levels after nasal lipopolysaccharide (LPS) challenge
Nasal mucosal IL-6 levels after LPS challenge (area under curve, 0 to 8h) will be compared to placebo responses (AUC, 0-8h) in nasal mucosal lining fluid
Measured: Up to 8h after nasal LPS challenge
Nasal mucosal lining fluid CXCL8 levels after nasal lipopolysaccharide (LPS)
Nasal mucosal CXCL8 levels after LPS challenge (area under curve, 0 to 8h) will be compared to placebo responses (AUC, 0-8h) in nasal mucosal lining fluid
Measured: Up to 8h after nasal LPS challenge
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Nov 2014 (estimated)
- Study startOct 2010
- Primary completionApr 2011
- Study completionApr 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (32)Papers the sponsor has linked to this study.
- Other trials for HealthyStudies of the same condition, open and under way.
- More trials run by Imperial College LondonThe 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
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Imperial College London
- Sponsor type
- University, hospital or other
- Collaborators
- GlaxoSmithKline
- Responsible party
- Sponsor
- Investigators
- Trevor T Hansel, FRCPath, PhD, Principal investigator, Imperial College London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02284074
- Sponsor's protocol ID
- ICRRU/2010/001
- Other IDs
- 10/H0803/110, ICRRU/2010/001
- Status last verified
- Sep 2023
- First submitted
- 19 Sep 2014
- Last updated
- 15 Sep 2023
- Results posted
- No
- Data monitoring committee
- No
Publications
Barnes PJ. Immunology of asthma and chronic obstructive pulmonary disease. Nat Rev Immunol. 2008 Mar;8(3):183-92. doi: 10.1038/nri2254. Epub 2008 Feb 15.
PubMed 18274560Anderson GP. Endotyping asthma: new insights into key pathogenic mechanisms in a complex, heterogeneous disease. Lancet. 2008 Sep 20;372(9643):1107-19. doi: 10.1016/S0140-6736(08)61452-X.
PubMed 18805339Calverley PM, Rennard SI. What have we learned from large drug treatment trials in COPD? Lancet. 2007 Sep 1;370(9589):774-85. doi: 10.1016/S0140-6736(07)61381-6.
PubMed 17765527Fukata M, Vamadevan AS, Abreu MT. Toll-like receptors (TLRs) and Nod-like receptors (NLRs) in inflammatory disorders. Semin Immunol. 2009 Aug;21(4):242-53. doi: 10.1016/j.smim.2009.06.005.
PubMed 19748439O'Neill LA, Bryant CE, Doyle SL. Therapeutic targeting of Toll-like receptors for infectious and inflammatory diseases and cancer. Pharmacol Rev. 2009 Jun;61(2):177-97. doi: 10.1124/pr.109.001073. Epub 2009 May 27.
PubMed 19474110Chanez P, Vignola AM, Vic P, Guddo F, Bonsignore G, Godard P, Bousquet J. Comparison between nasal and bronchial inflammation in asthmatic and control subjects. Am J Respir Crit Care Med. 1999 Feb;159(2):588-95. doi: 10.1164/ajrccm.159.2.9801022.
PubMed 9927377American Thoracic Society Workshop. Immunobiology of asthma and rhinitis. Pathogenic factors and therapeutic options. Am J Respir Crit Care Med. 1999 Nov;160(5 Pt 1):1778-87. doi: 10.1164/ajrccm.160.5.ats7-99. No abstract available.
PubMed 10556156Linden M, Svensson C, Andersson E, Andersson M, Greiff L, Persson CG. Immediate effect of topical budesonide on allergen challenge-induced nasal mucosal fluid levels of granulocyte-macrophage colony-stimulating factor and interleukin-5. Am J Respir Crit Care Med. 2000 Nov;162(5):1705-8. doi: 10.1164/ajrccm.162.5.9910094.
PubMed 11069800Alam R, Sim TC, Hilsmeier K, Grant JA. Development of a new technique for recovery of cytokines from inflammatory sites in situ. J Immunol Methods. 1992 Oct 19;155(1):25-9. doi: 10.1016/0022-1759(92)90267-w.
PubMed 1401965Greiff L, Pipkorn U, Alkner U, Persson CG. The 'nasal pool' device applies controlled concentrations of solutes on human nasal airway mucosa and samples its surface exudations/secretions. Clin Exp Allergy. 1990 May;20(3):253-9. doi: 10.1111/j.1365-2222.1990.tb02680.x.
PubMed 2364306Howarth PH, Persson CG, Meltzer EO, Jacobson MR, Durham SR, Silkoff PE. Objective monitoring of nasal airway inflammation in rhinitis. J Allergy Clin Immunol. 2005 Mar;115(3 Suppl 1):S414-41. doi: 10.1016/j.jaci.2004.12.1134.
PubMed 15746881Chawes BL, Edwards MJ, Shamji B, Walker C, Nicholson GC, Tan AJ, Folsgaard NV, Bonnelykke K, Bisgaard H, Hansel TT. A novel method for assessing unchallenged levels of mediators in nasal epithelial lining fluid. J Allergy Clin Immunol. 2010 Jun;125(6):1387-1389.e3. doi: 10.1016/j.jaci.2010.01.039. Epub 2010 Mar 20. No abstract available.
PubMed 20304470Lin RY, Nahal A, Lee M, Menikoff H. Cytologic distinctions between clinical groups using curette-probe compared to cytology brush. Ann Allergy Asthma Immunol. 2001 Feb;86(2):226-31. doi: 10.1016/S1081-1206(10)62696-8.
PubMed 11258695Dreskin SC, Dale SN, Foster SM, Martin D, Buchmeier A, Nelson HS. Measurement of changes in mRNA for IL-5 in noninvasive scrapings of nasal epithelium taken from patients undergoing nasal allergen challenge. J Immunol Methods. 2002 Oct 15;268(2):189-95. doi: 10.1016/s0022-1759(02)00206-5.
PubMed 12215387Proud D, Turner RB, Winther B, Wiehler S, Tiesman JP, Reichling TD, Juhlin KD, Fulmer AW, Ho BY, Walanski AA, Poore CL, Mizoguchi H, Jump L, Moore ML, Zukowski CK, Clymer JW. Gene expression profiles during in vivo human rhinovirus infection: insights into the host response. Am J Respir Crit Care Med. 2008 Nov 1;178(9):962-8. doi: 10.1164/rccm.200805-670OC. Epub 2008 Jul 24.
PubMed 18658112
Study at a glance
From the registry record, last updated by the sponsor on 15 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Nasal Lipopolysaccharide (LPS) Challenge in Healthy Volunteers (HVs): Investigation of Tolerability, Dose Response and the Expression Profile of Intercellular Adhesion Molecule-1 (ICAM-1)
- ClinicalTrials.gov ID
- NCT02284074
- Acronym / sponsor ID
- ICRRU/2010/001
- Conditions
- Healthy
- Keywords
- Lipopolysaccharide (LPS), Biomarkers, Chemokines, Cytokines, Gene Expression, Nasal Challenge, Inflammation, Nasal
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Imperial College LondonUniversity, hospital or other
- Collaborators
- GlaxoSmithKline
- Study start
- Oct 2010
- Primary completion
- Apr 2011 (actual)
- Study completion
- Apr 2011 (actual)
- First posted
- 5 Nov 2014 (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.
The purpose of this study is to develop a nasal challenge model that causes a mild degree of inflammation, without causing any pain or symptoms, but that allows us to measure a variety of proteins in nasal secretions which causes inflammation in the nose. The nasal challenge model involves spraying the nostrils in the form of a fine mist with 4 different doses (1, 10, 30 and 100µg per nostril) of lipopolysaccharide (LPS) including a placebo. LPS is a type of protein which has been carefully purified from the outer cell wall of certain bacteria, is sterile and does not contain live bacteria, and will not cause infection.
The investigators will measure any inflammation in the nose by looking at cells collected by washing the inside of the nose (nasal lavage) and placing small strips of paper in the nasal cavity. The paper absorbs the nasal fluid and the chemicals produced during inflammation and can be extracted from the paper and analysed in the laboratory. The investigators will also be collecting a small amount of nasal epithelium taken by way of a nasal scrape; this is done by using a Rhinoprobe, a small plastic curette which is used to scrape a small piece of lining of the nose. The investigators hope that information obtained from this study will be used in future studies that will test new study drugs designed to treat diseases of the airways and lungs ( like asthma and chronic obstructive pulmonary disease (COPD) and hay fever.
Detailed description
STUDY DESIGN AND METHODOLOGY This is a single-centre study which will be carried out at the Imperial Clinical Respiratory Research Unit (ICRRU) at St Mary's Hospital in London Paddington.
RECRUITMENT The study will recruit a total of 15 healthy participants.
STUDY VISITS The study will involve a total of 11 outpatients visits. The screening visit is the initial visit where the study is discussed with the participant and written informed consent is obtained by the PI or his designee. This is done prior to performing any study related procedures. The participant will have had the study information sheet for at least 24 hours prior to the visit.
The visit will include the collection of demographic data, height and weight, physical examination by a doctor, medical history, vital signs, body temperature, 12 lead ECG, laboratory assessments (safety bloods) urine drugs of abuse test and pregnancy tests for females. The participant will also be asked to indicate the presence of any nasal symptoms by completing a modified total nasal symptoms score sheet and perform a peak nasal inspiratory flow (PNIF) test.
If eligible, participants will be asked to return for further study visits. Participants will be given 4 different doses of LPS and a placebo in a randomised manner.
There are a total of 5 treatment periods. Each treatment period consists of a 11h visit the first day and a 20 minute visit the following day. There is a total of 12-28 days interval between each treatment period visit.
During the treatment period visits, the study participants will undergo the following study procedures:
- Nasal lavage to both nostrils and discard with 5ml of 0.9% saline in order to clean the nose prior to nasal LPS challenge.
- Nasal challenge with LPS (placebo, 1,10, 30 or 100µg per nostril)
- Nasosorption (right nostril) at -30m, +30m, +1h, then hourly to 10h and 24h
- Nasal lavage (left nostril) at -30m, +2h, +4h, +8h, +24h
- Nasal scrape (left nostril) at -30m, +3h, +6h, +24h
- Modified total nasal symptom score (TNSS) at -30m, +30m, +1h, then hourly to 10h and 24h
- Peak nasal inspiratory flow (PNIF) rate at -30m, +2h, +4h, +8h, 24h
- Systemic adverse events
- Temperature (oral) at -30m, +2h, +4h, +8h
- Blood pressure and heart rate at -30m
- Females of child bearing potential will have a pregnancy test performed.
NASAL PROCEDURES IN THE STUDY
- Nasal washing (nasal lavage): Nasal washings in the nose are carried out by passing a small volume of salt water (saline) fluid into the nose. A nasal adapter shaped like an olive is placed inside the nostril. The participant is then asked to sit forward and the salty water solution (saline) is used to flush in and out of the nose over a one minute period. This procedure is carried out on both nostrils to clean up the nose on the initial study visit and then repeated only on the left nostril on each treatment visit.
- Nasal lining fluid absorption (nasosorption or SAM): A small strip of absorbent material, that looks and feels like soft tissue paper, will be used to absorb moisture from the inside surface of the nostril. The special absorptive paper will be placed inside the nostril and left for a period of 2 minutes to absorb the nasal lining fluid before being removed, gently sucking up fluid like blotting paper. Putting the paper into the nose can tickle, and cause your eyes to water a little. However, the nasosorption does not hurt and the investigators method has proved to be well tolerated in babies, children and adults. The paper absorbs the nasal fluid and many substances produced by the nasal cells can then be extracted from the paper and measured in the laboratory.
- Nasal scrape (nasal curettage or Rhinoprobe): A small sterile disposable plastic probe will be inserted into the nose and will be gently pressed against the inside surface lining of the nostril. The 3 inch long probe has a tiny scoop on the end, which can barely be see. 24 tiny samples from each nostril (a pinhead, 2mm, of tissue) will be taken from a part of the nose that has a reduced nerve supply to limit any discomfort. Taking this sample does not cause bleeding, but may cause some mild discomfort, and may make the eyes water slightly. The probe will collect nasal cells from the surface of the nostril which will then be sent for analysis. This method has been performed on many adults, children, and babies, and has been very well tolerated.
STATISTICAL ANALYSIS Each of the measures will be summarised descriptively by dose and time using appropriate summary statistics. If appropriate, response variables will be transformed (e.g. log-transformed). Gene expression data will be normalised by house-keeper gene. The TNSS will be calculated by summing the scores of nasal blockage, nasal discharge/rhinorrhoea, nasal burning/itching/pain sensation, and sneezing at each timepoint. Weighted means of symptom scores will be calculated over the time interval 0 to 10h.
TNSS, nasal sniff pressures, nasosorption measures and gene expression data from the nasal scrapes will each be plotted against time, with a separate plot for each subject and measure, and with LPS dose and placebo represented by separate lines on the plots. Summary statistics (e.g. mean +/- 95% confidence intervals or median and interquartile range) for nasal lavage and gene expression data will be plotted by dose against time.
Correlations will be explored using scatter plots for the following measures:
- Weighted means TNSS vs. maximum TNF-α
- Weighted means TNSS vs. maximum IL-8
- Weighted means TNSS vs. maximum s-ICAM-1
- Maximum ICAM-1 expression vs. maximum TNF-α
Reproducibility of the nasal LPS challenge for ICAM-1 expression and TNF-α will be explored using the following subsets of data:
- Predose data for each period to explore intra-subject variability. Parameter vs. period number will be plotted with a separate line for each subject to explore whether there is a period effect. Box and whisker plots will also be used to summarise the parameter by period.
- Placebo period data - Parameter vs time will be plotted with a separate line for each subject to explore whether there is a time-course effect. Box and whisker plots will also be used to summarise the parameter over time.
Box and whisker plots for ICAM-1 expression and TNF-α and dose and time will be presented to investigate whether these measures return to baseline after 24h.
Additional exploratory analyses may be performed to further characterize the expression profile of ICAM following nasal LPS challenge.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Nasal LPS spray - placebo | Experimental | Other: Nasal LPS sprayThis is a 5-way crossover, randomised, placebo-controlled study. Arms consists of the following nasal challenges: placebo, 1, 10, 30 and 100µg LPS. |
| Nasal LPS spray 1µg | Experimental | Other: Experimental: Nasal LPS spray 1µgThis is a 5-way crossover, randomised, placebo-controlled study. Arms consists of the following nasal challenges: placebo, 1, 10, 30 and 100µg LPS. |
| Nasal LPS spray 10 µg | Experimental | Other: Experimental: Nasal LPS spray 10 µgThis is a 5-way crossover, randomised, placebo-controlled study. Arms consists of the following nasal challenges: placebo, 1, 10, 30 and 100µg LPS. |
| Nasal LPS spray 30 µg | Experimental | Other: Experimental: Nasal LPS spray 30 µgThis is a 5-way crossover, randomised, placebo-controlled study. Arms consists of the following nasal challenges: placebo, 1, 10, 30 and 100µg LPS. |
| Nasal LPS spray 100 µg | Experimental | Other: Experimental: Nasal LPS spray 100 µgThis is a 5-way crossover, randomised, placebo-controlled study. Arms consists of the following nasal challenges: placebo, 1, 10, 30 and 100µg LPS. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- Males and females aged 18 to 60 years
- Current non-smokers for last 6 months (<5 cigs per week), with a smoking history of <5 pack years
- BMI 20-30 kg/m2
Key exclusion criteria (12 listed)
- History of allergy
- Upper airway infection in 2 weeks before screening
- Lower respiratory tract infection in past 3 months
- Treatment with local or systemic corticosteroids during previous 2 months
- Signs or symptoms of chronic rhinitis, hypertrophy of turbinates, major septum deviation, nasal polyposis or recurrent sinusitis
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 |
|---|---|---|
| Nasal LPS sprayLPS solution (250µl) will be prepared at 10, 100, 300 and 1000µg/ml, 100µl is administered to each nostril, both nostrils will be sprayed. The dose per nostril corresponds to 1, 10, 30 and 100µg. | Other | Nasal LPS spray - placebo |
| Experimental: Nasal LPS spray 1µgLPS solution (250µl) will be prepared at 10, 100, 300 and 1000µg/ml, 100µl is administered to each nostril, both nostrils will be sprayed. | Other | Nasal LPS spray 1µg |
| Experimental: Nasal LPS spray 10 µgLPS solution (250µl) will be prepared at 10, 100, 300 and 1000µg/ml, 100µl is administered to each nostril, both nostrils will be sprayed. | Other | Nasal LPS spray 10 µg |
| Experimental: Nasal LPS spray 30 µgLPS solution (250µl) will be prepared at 10, 100, 300 and 1000µg/ml, 100µl is administered to each nostril, both nostrils will be sprayed. | Other | Nasal LPS spray 30 µg |
| Experimental: Nasal LPS spray 100 µgLPS solution (250µl) will be prepared at 10, 100, 300 and 1000µg/ml, 100µl is administered to each nostril, both nostrils will be sprayed. | Other | Nasal LPS spray 100 µg |
Primary outcome
Level of nasal mucosal inter-cellular adhesion molecule-1 (ICAM-1) by gene expression analysis
Time frame: 8 hours following nasal lipopolysaccharide (LPS) challenge
Measurement of gene expression (mRNA) for inter-cellular adhesion molecule-1 (ICAM-1) in nasal mucosal curettage samples, 8h following nasal lipopolysaccharide (LPS) challenge.
3 secondary outcomes
Nasal mucosal lining fluid IL-1beta levels after nasal lipopolysaccharide (LPS) challenge
Time frame: Up to 8h after nasal LPS challenge
Nasal mucosal lining fluid IL-6 levels after nasal lipopolysaccharide (LPS) challenge
Time frame: Up to 8h after nasal LPS challenge
Nasal mucosal lining fluid CXCL8 levels after nasal lipopolysaccharide (LPS)
Time frame: Up to 8h after nasal LPS challenge
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 Sep 2023.
- Background: PubMed 18274560Barnes PJ. Immunology of asthma and chronic obstructive pulmonary disease. Nat Rev Immunol. 2008 Mar;8(3):183-92. doi: 10.1038/nri2254. Epub 2008 Feb 15.
- Background: PubMed 18805339Anderson GP. Endotyping asthma: new insights into key pathogenic mechanisms in a complex, heterogeneous disease. Lancet. 2008 Sep 20;372(9643):1107-19. doi: 10.1016/S0140-6736(08)61452-X.
- Background: PubMed 17765527Calverley PM, Rennard SI. What have we learned from large drug treatment trials in COPD? Lancet. 2007 Sep 1;370(9589):774-85. doi: 10.1016/S0140-6736(07)61381-6.
- Background: PubMed 19748439Fukata M, Vamadevan AS, Abreu MT. Toll-like receptors (TLRs) and Nod-like receptors (NLRs) in inflammatory disorders. Semin Immunol. 2009 Aug;21(4):242-53. doi: 10.1016/j.smim.2009.06.005.
- Background: PubMed 19474110O'Neill LA, Bryant CE, Doyle SL. Therapeutic targeting of Toll-like receptors for infectious and inflammatory diseases and cancer. Pharmacol Rev. 2009 Jun;61(2):177-97. doi: 10.1124/pr.109.001073. Epub 2009 May 27.
- Background: PubMed 9927377Chanez P, Vignola AM, Vic P, Guddo F, Bonsignore G, Godard P, Bousquet J. Comparison between nasal and bronchial inflammation in asthmatic and control subjects. Am J Respir Crit Care Med. 1999 Feb;159(2):588-95. doi: 10.1164/ajrccm.159.2.9801022.
- Background: PubMed 10556156American Thoracic Society Workshop. Immunobiology of asthma and rhinitis. Pathogenic factors and therapeutic options. Am J Respir Crit Care Med. 1999 Nov;160(5 Pt 1):1778-87. doi: 10.1164/ajrccm.160.5.ats7-99. No abstract available.
- Background: PubMed 11069800Linden M, Svensson C, Andersson E, Andersson M, Greiff L, Persson CG. Immediate effect of topical budesonide on allergen challenge-induced nasal mucosal fluid levels of granulocyte-macrophage colony-stimulating factor and interleukin-5. Am J Respir Crit Care Med. 2000 Nov;162(5):1705-8. doi: 10.1164/ajrccm.162.5.9910094.
- Background: PubMed 1401965Alam R, Sim TC, Hilsmeier K, Grant JA. Development of a new technique for recovery of cytokines from inflammatory sites in situ. J Immunol Methods. 1992 Oct 19;155(1):25-9. doi: 10.1016/0022-1759(92)90267-w.
- Background: PubMed 2364306Greiff L, Pipkorn U, Alkner U, Persson CG. The 'nasal pool' device applies controlled concentrations of solutes on human nasal airway mucosa and samples its surface exudations/secretions. Clin Exp Allergy. 1990 May;20(3):253-9. doi: 10.1111/j.1365-2222.1990.tb02680.x.
- Background: PubMed 15746881Howarth PH, Persson CG, Meltzer EO, Jacobson MR, Durham SR, Silkoff PE. Objective monitoring of nasal airway inflammation in rhinitis. J Allergy Clin Immunol. 2005 Mar;115(3 Suppl 1):S414-41. doi: 10.1016/j.jaci.2004.12.1134.
- Background: PubMed 20304470Chawes BL, Edwards MJ, Shamji B, Walker C, Nicholson GC, Tan AJ, Folsgaard NV, Bonnelykke K, Bisgaard H, Hansel TT. A novel method for assessing unchallenged levels of mediators in nasal epithelial lining fluid. J Allergy Clin Immunol. 2010 Jun;125(6):1387-1389.e3. doi: 10.1016/j.jaci.2010.01.039. Epub 2010 Mar 20. No abstract available.
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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.
Trevor T Hansel, FRCPath, PhD principal investigator
Imperial College London
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Nasal LPS spray, Experimental: Nasal LPS spray 1µg and Experimental: Nasal LPS spray 10 µg in people with Healthy, run by Imperial College London at 1 site in United Kingdom.
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 Sep 2023. 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 United Kingdom. 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 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?
Level of nasal mucosal inter-cellular adhesion molecule-1 (ICAM-1) by gene expression analysis (time frame: 8 hours following nasal lipopolysaccharide (LPS) challenge). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02284074, which also lists 32 linked publications.
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 Sep 2023.