Ignite Creation Date:
2024-05-06 @ 5:37 PM
Last Modification Date:
2024-10-26 @ 2:32 PM
Study NCT ID:
NCT05378594
Status:
UNKNOWN
Last Update Posted:
2022-11-03
First Post:
2022-05-12
Brief Title:
HDM and Silver Birch NAC Standardisation
Sponsor:
Royal Brompton Harefield NHS Foundation Trust
Organization:
Royal Brompton Harefield NHS Foundation Trust
Study Overview
Official Title:
Nasal Allergen Challenge Standardisation for House Dust Mite and Silver Birch Allergen Extracts
Status:
UNKNOWN
Status Verified Date:
2022-10
Last Known Status:
RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This study aims to establish dose-responses to nasal allergen challenge using silver birch pollen and house dust mite allergen extracts in participants with allergic rhinitis sensitised to either or both of these allergens The allergen extracts used will be Itulazax tablets silver birch pollen allergen sublingual tablets ALK-Abello Denmark and Acarizax tablets house dust mite allergen sublingual tablets ALK-Abello Denmark The results will allow identification of the dose of each allergen typically producing a moderate severity response which could then be used in future interventional and investigational studies
A control group - healthy individuals with no allergic rhinitis - will be recruited to demonstrate the absence of an irritantnon-allergic effect of the nasal allergen challenge procedure
A control group - healthy individuals with no allergic rhinitis - will be recruited to demonstrate the absence of an irritantnon-allergic effect of the nasal allergen challenge procedure
Detailed Description:
Nasal allergen challenge NAC is a useful tool in the investigation of allergic rhinitis including grass pollen-induced seasonal allergic rhinitis hay fever The investigators have experience in using NAC to investigate the clinical and immunological effects of allergen exposure and in using NAC as a surrogate outcome to assess the efficacy of treatments for allergic rhinitis The procedure is safe and well tolerated
For NAC to be a valid tool it is essential that the allergen extracts used are standardised in terms of concentration and stability in solution The investigators recently undertook a study comparing the effects of two different grass pollen allergen extracts when used for NAC The investigators found that the use of a lyophilizate pollen tablet designed for sublingual immunotherapy treatment was a suitable alternative to using dissolved dry powder allergen designed for subcutaneous immunotherapy treatment The study was necessary because the dry powder product was being phased out by the manufacturer
The investigators now intend to undertake a similar study using lyophilizate tablets for two further common environmental allergens house dust mite and silver birch tree pollen The products used will be as follows Acarizax House Dust Mite lyophilizate tablet and Itulazax Silver Birch Pollen lyophilizate tablet both manufactured by ALK-Abello Denmark
House dust mite HDM is the most common indoor allergen trigger in individuals with allergic rhinitis and allergic asthma in the UK silver birch SB pollen is a common cause of springtime hay fever This will allow us to determine the suitability of using lyophilizate tablets as an allergen source for NAC for these two allergens in future interventional studies
In this study the investigators will recruit 20 volunteers with house dust mite induced allergic rhinitis - controlled asthma and 20 volunteers with silver birch pollen induced allergic rhinitis - controlled asthma individuals allergic to both allergens will be eligible for both parts of the study HDM allergic volunteers will undergo a graded up-dosing NAC with HDM allergen tablet extract SB allergic volunteers will undergo a graded up-dosing NAC with SB allergen tablet extract dual allergic individuals will be given the option of undergoing challenges to both allergens at least 4 weeks apart
Recorded outcomes will include the participant-reported symptom score total nasal symptom score TNSS range 0-12 and peak nasal inspiratory flow PNIF Lmin during the NAC The primary endpoint will be the area under the curve for TNSS during NAC with each allergen Secondary endpoints will include area under the curve for change from baseline PNIF during NAC the modal allergen dose required to give a TNSS of 712 provoking dose 7 peak TNSS score maximal fall in PNIF and the absolute sneeze count
Following the above the investigators will then undertake nasal challenges using the identified provoking dose 7 for each allergen on 5 individuals from the other part of the cohort ie test the HDM provoking dose 7 on 5 of the participants with SB allergy but no HDM allergy and vice versa and also on 5 non-atopic individuals no history of allergic rhinitis or asthma negative skin tests to common environmental allergens to prove the NAC is allergen specific and non-irritant
The study will have two arms one for HDM allergic individuals one for SB allergic individuals running concurrently Dual allergic individuals may be included in both arms Within each arm up to 20 participants will undergo NAC with the relevant allergen The NAC procedure will involve baseline TNSS and PNIF scores prior to intervention then the same scores at 10 minutes after challenges with allergen at the following concentrations 0 BUmL saline 1 0 BUmL saline 2 100 BUmL 500 BUmL 1500 BUmL 5000 BUmL 10000 BUmL with 15 minutes between doses Area under the curve for TNSS will be calculated for each NAC along with the first concentration provoking a TNSS of 712 The NAC will continue to the top concentration of 10000 BUmL regardless of TNSS score unless the participant has very bothersome symptoms and prefers not to continue
For individuals allergic to both allergens a minimum gap of 4 weeks will be required between the two NACs
Following completion of the above and identification of the provoking dose 7 for each allergen 5 single-sensitised ie HDM or SB but not both participants will return for a further NAC with the allergen to which they are not sensitised a minimum of 4 weeks after their last NAC The procedure will involve baseline TNSS and PNIF scores prior to intervention then the same scores at 10 minutes after challenges with allergen at the following concentrations 0 BUmL saline 1 provoking dose 7 BUmL Additionally 5 non-atopic individuals will be recruited to attend for a single visit for NAC as follows 0 BUmL saline 1 provoking dose 7 for HDM BUmL 0 BUmL saline 2 provoking dose 7 for SB BUmL with TNSS and PNIF measured as before
Individuals with a history of seasonal allergic rhinitis in February-May andor a history of perennial allergic rhinitis suspected to be provoked by house dust mite exposure for at least the past two years will be invited for screening Volunteers will need to avoid taking antihistamines for 5 days prior to screening to allow for skin testing Up to forty volunteers fewer if individuals are dual allergic and wish to take part in both arms of the study who pass the inclusion and exclusion criteria see below and are willing to provide written informed consent will be enrolled into the study A minimum of five non-atopic individuals with no history of rhinitis who pass the inclusion and exclusion criteria see below will be enrolled into the control arm of the study They will then undertake a single visit as above
Single allergen allergic individuals will undertake 1-2 visits after screening Visit 1 all challenge to relevant allergen Visit 2 a minimum of 5 challenge to irrelevant allergen
Dual allergen allergic individuals will undertake 1-2 visits after screening Visit 1 all challenge to allergen identified by participant and study doctor as the primary cause of their symptoms Visit 2 as per participants preference challenge to the other allergen
Non-atopic volunteers will undertake a single visit after screening
For NAC to be a valid tool it is essential that the allergen extracts used are standardised in terms of concentration and stability in solution The investigators recently undertook a study comparing the effects of two different grass pollen allergen extracts when used for NAC The investigators found that the use of a lyophilizate pollen tablet designed for sublingual immunotherapy treatment was a suitable alternative to using dissolved dry powder allergen designed for subcutaneous immunotherapy treatment The study was necessary because the dry powder product was being phased out by the manufacturer
The investigators now intend to undertake a similar study using lyophilizate tablets for two further common environmental allergens house dust mite and silver birch tree pollen The products used will be as follows Acarizax House Dust Mite lyophilizate tablet and Itulazax Silver Birch Pollen lyophilizate tablet both manufactured by ALK-Abello Denmark
House dust mite HDM is the most common indoor allergen trigger in individuals with allergic rhinitis and allergic asthma in the UK silver birch SB pollen is a common cause of springtime hay fever This will allow us to determine the suitability of using lyophilizate tablets as an allergen source for NAC for these two allergens in future interventional studies
In this study the investigators will recruit 20 volunteers with house dust mite induced allergic rhinitis - controlled asthma and 20 volunteers with silver birch pollen induced allergic rhinitis - controlled asthma individuals allergic to both allergens will be eligible for both parts of the study HDM allergic volunteers will undergo a graded up-dosing NAC with HDM allergen tablet extract SB allergic volunteers will undergo a graded up-dosing NAC with SB allergen tablet extract dual allergic individuals will be given the option of undergoing challenges to both allergens at least 4 weeks apart
Recorded outcomes will include the participant-reported symptom score total nasal symptom score TNSS range 0-12 and peak nasal inspiratory flow PNIF Lmin during the NAC The primary endpoint will be the area under the curve for TNSS during NAC with each allergen Secondary endpoints will include area under the curve for change from baseline PNIF during NAC the modal allergen dose required to give a TNSS of 712 provoking dose 7 peak TNSS score maximal fall in PNIF and the absolute sneeze count
Following the above the investigators will then undertake nasal challenges using the identified provoking dose 7 for each allergen on 5 individuals from the other part of the cohort ie test the HDM provoking dose 7 on 5 of the participants with SB allergy but no HDM allergy and vice versa and also on 5 non-atopic individuals no history of allergic rhinitis or asthma negative skin tests to common environmental allergens to prove the NAC is allergen specific and non-irritant
The study will have two arms one for HDM allergic individuals one for SB allergic individuals running concurrently Dual allergic individuals may be included in both arms Within each arm up to 20 participants will undergo NAC with the relevant allergen The NAC procedure will involve baseline TNSS and PNIF scores prior to intervention then the same scores at 10 minutes after challenges with allergen at the following concentrations 0 BUmL saline 1 0 BUmL saline 2 100 BUmL 500 BUmL 1500 BUmL 5000 BUmL 10000 BUmL with 15 minutes between doses Area under the curve for TNSS will be calculated for each NAC along with the first concentration provoking a TNSS of 712 The NAC will continue to the top concentration of 10000 BUmL regardless of TNSS score unless the participant has very bothersome symptoms and prefers not to continue
For individuals allergic to both allergens a minimum gap of 4 weeks will be required between the two NACs
Following completion of the above and identification of the provoking dose 7 for each allergen 5 single-sensitised ie HDM or SB but not both participants will return for a further NAC with the allergen to which they are not sensitised a minimum of 4 weeks after their last NAC The procedure will involve baseline TNSS and PNIF scores prior to intervention then the same scores at 10 minutes after challenges with allergen at the following concentrations 0 BUmL saline 1 provoking dose 7 BUmL Additionally 5 non-atopic individuals will be recruited to attend for a single visit for NAC as follows 0 BUmL saline 1 provoking dose 7 for HDM BUmL 0 BUmL saline 2 provoking dose 7 for SB BUmL with TNSS and PNIF measured as before
Individuals with a history of seasonal allergic rhinitis in February-May andor a history of perennial allergic rhinitis suspected to be provoked by house dust mite exposure for at least the past two years will be invited for screening Volunteers will need to avoid taking antihistamines for 5 days prior to screening to allow for skin testing Up to forty volunteers fewer if individuals are dual allergic and wish to take part in both arms of the study who pass the inclusion and exclusion criteria see below and are willing to provide written informed consent will be enrolled into the study A minimum of five non-atopic individuals with no history of rhinitis who pass the inclusion and exclusion criteria see below will be enrolled into the control arm of the study They will then undertake a single visit as above
Single allergen allergic individuals will undertake 1-2 visits after screening Visit 1 all challenge to relevant allergen Visit 2 a minimum of 5 challenge to irrelevant allergen
Dual allergen allergic individuals will undertake 1-2 visits after screening Visit 1 all challenge to allergen identified by participant and study doctor as the primary cause of their symptoms Visit 2 as per participants preference challenge to the other allergen
Non-atopic volunteers will undertake a single visit after screening
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
None