Leukotriene D4 Nasal Provocation Test in Allergic Rhinitis

Asthma Clinical Trial

Official title:

Leukotriene D4 Nasal Provocation Test: Rationale, Methodology, Diagnostic Value and Its Impact on Airway Inflammation in Allergic Rhinitis With or Without Asthma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01963741
• Other study ID #: LTD4NAPT201218
• Status: Completed
• Phase: N/A
• First received: August 27, 2013
• Last updated: July 8, 2015
• Start date: November 2012
• Est. completion date: April 2014

Study information

• Verified date: July 2015
• Source: Guangzhou Institute of Respiratory Disease
• Contact: n/a
• Is FDA regulated: No
• Health authority: China: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

Leukotrienes play critical roles in the inflammatory process in allergic rhinitis and bronchial asthma, therefore, anti-leukotriene therapy is part of treatment for asthma. However, not all allergic rhinitis accompanied with or without asthma treated with anti-leukotriene were effective. So it is critical to develop a method to identify the response subgroup. In this study, it is assumed that nasal physiological responsiveness to leukotriene nasal provocation test (NPT) is able to gain evidence on the effect of leukotriene on the development of allergic rhinitis and asthma, and is helpful to the use of anti-leukotriene agent. The purpose of the study is to establish the methodology and diagnostic value of leukotriene D4 (LTD4) nasal provocation.

Description:

Nasal provocation test induced by LTD4 will be conducted by measuring nasal airway resistance and airway symptoms in a stepwise concentration of LTD4 by nasal spray. Inflammation biomarkers, such as eosinophilic granulocyte in sputum and nasal lavage, fractional exhaled nitric oxide(FeNO), and lung function before and after nasal provocation will be studied to explore the impact of LTD4 nasal provocation test on airway inflammation.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: April 2014
• Est. primary completion date: February 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 50 Years

Eligibility

Inclusion Criteria:

• Patients with allergic rhinitis accompanied with or without asthma

• positive skin prick test (SPT)

• had no acute upper or lower airway infection 2 weeks prior to study

• no oral or nasal anti-histamines

• no leukotriene receptor antagonists for 1 week

• no oral or nasal and inhaled corticosteroids for 2 weeks

Exclusion Criteria:

• smokers

• a past confirmed history of chronic respiratory disease other than asthma

• other severe systemic diseases (myocardial infarction, malignant tumor, etc.)

• under immunotherapy

• unable to complete the test or had limited understanding

• pregnancy

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Single Blind (Subject), Primary Purpose: Diagnostic

Related Conditions & MeSH terms

• Allergic Rhinitis
• Asthma
• Rhinitis

Intervention

Drug:
• leukotriene D4
Nasal challenge using 16% ethanol diluent, the concentration of which corresponded to the highest concentration of LTD4, was undertaken for exclusion of subjects hypersensitive to ethanol or saline. The LTD4 challenge could be initiated provided that NAR increase was <30%. Ranges of 4 to 16 mcg.mL-1 LTD4 diluents were applied for a double-fold increment approach at intervals of 6 minutes.
• histamine
Nasal challenge using 0.9% saline, was undertaken for exclusion of subjects hypersensitive to saline. The histamine nasal challenge could be initiated provided that NAR increase was <30%. Ranges of 0.4 to 3.2 mg.mL-1 histamine diluents were applied for a double-fold increment approach at intervals of 3 minutes.

Locations

Country	Name	City	State
China	Guangzhou institute of respiratory disease	Guangzhou	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Guangzhou Institute of Respiratory Disease

Country where clinical trial is conducted

China, 

References & Publications (14)

Bisgaard H, Olsson P, Bende M. Effect of leukotriene D4 on nasal mucosal blood flow, nasal airway resistance and nasal secretion in humans. Clin Allergy. 1986 Jul;16(4):289-97. — View Citation

Brozek JL, Baena-Cagnani CE, Bonini S, Canonica GW, Rasi G, van Wijk RG, Zuberbier T, Guyatt G, Bousquet J, Schünemann HJ. Methodology for development of the Allergic Rhinitis and its Impact on Asthma guideline 2008 update. Allergy. 2008 Jan;63(1):38-46. Review. — View Citation

Busse WW. The role of leukotrienes in asthma and allergic rhinitis. Clin Exp Allergy. 1996 Aug;26(8):868-79. Review. — View Citation

Guan W, Zheng J, Gao Y, Jiang C, An J, Yu X, Liu W. Leukotriene D4 bronchial provocation test: methodology and diagnostic value. Curr Med Res Opin. 2012 May;28(5):797-803. doi: 10.1185/03007995.2012.678936. Epub 2012 May 3. — View Citation

Guan W, Zheng J, Gao Y, Jiang C, Xie Y, An J, Yu X, Liu W, Zhong N. Leukotriene D4 and methacholine bronchial provocation tests for identifying leukotriene-responsiveness subtypes. J Allergy Clin Immunol. 2013 Feb;131(2):332-8.e1-4. doi: 10.1016/j.jaci.2012.08.020. Epub 2012 Oct 4. — View Citation

Howarth PH, Salagean M, Dokic D. Allergic rhinitis: not purely a histamine-related disease. Allergy. 2000;55 Suppl 64:7-16. Review. — View Citation

Miadonna A, Tedeschi A, Leggieri E, Lorini M, Folco G, Sala A, Qualizza R, Froldi M, Zanussi C. Behavior and clinical relevance of histamine and leukotrienes C4 and B4 in grass pollen-induced rhinitis. Am Rev Respir Dis. 1987 Aug;136(2):357-62. — View Citation

Nayak A, Langdon RB. Montelukast in the treatment of allergic rhinitis: an evidence-based review. Drugs. 2007;67(6):887-901. Review. — View Citation

Patel P, Philip G, Yang W, Call R, Horak F, LaForce C, Gilles L, Garrett GC, Dass SB, Knorr BA, Reiss TF. Randomized, double-blind, placebo-controlled study of montelukast for treating perennial allergic rhinitis. Ann Allergy Asthma Immunol. 2005 Dec;95(6):551-7. — View Citation

Philip G, Williams-Herman D, Patel P, Weinstein SF, Alon A, Gilles L, Tozzi CA, Dass SB, Reiss TF. Efficacy of montelukast for treating perennial allergic rhinitis. Allergy Asthma Proc. 2007 May-Jun;28(3):296-304. — View Citation

Pinar E, Eryigit O, Oncel S, Calli C, Yilmaz O, Yuksel H. Efficacy of nasal corticosteroids alone or combined with antihistamines or montelukast in treatment of allergic rhinitis. Auris Nasus Larynx. 2008 Mar;35(1):61-6. Epub 2007 Sep 7. — View Citation

Price DB, Swern A, Tozzi CA, Philip G, Polos P. Effect of montelukast on lung function in asthma patients with allergic rhinitis: analysis from the COMPACT trial. Allergy. 2006 Jun;61(6):737-42. Erratum in: Allergy. 2006 Sep;61(9):1153. — View Citation

Riechelmann H, Bachert C, Goldschmidt O, Hauswald B, Klimek L, Schlenter WW, Tasman AJ, Wagenmann M; German Society for Allergology and Clinical Immunology (ENT Section); Working Team for Clinical Immunology. [Application of the nasal provocation test on diseases of the upper airways. Position paper of the German Society for Allergology and Clinical Immunology (ENT Section) in cooperation with the Working Team for Clinical Immunology]. Laryngorhinootologie. 2003 Mar;82(3):183-8. German. — View Citation

Virchow JC, Bachert C. Efficacy and safety of montelukast in adults with asthma and allergic rhinitis. Respir Med. 2006 Nov;100(11):1952-9. Epub 2006 Apr 12. — View Citation

* Note: There are 14 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change from baseline of cumulative dosage of methacholine causing a 20% fall in forced expiratory volume in 1 second (PD20FEV1-MCH)	The increase of brochial hyperresponsiveness induced by nasal provocation test was assessed by the decrease of cumulative dosage of methacholine causing a 20% fall in forced expiratory volume in 1 second (PD20FEV1-MCH).	Half an hour after nasal provocation test	Yes
Other	Peak Nasal Inspiratory Flow (PNIF)	The peak nasal inspiratory flow (PNIF) is measured by PNIF meter (in-check dial, Clement Clarke International Ltd.); Change from baseline of peak nasal inspiratory flow (PNIF) at the end of nasal provocation test will be reported.	3 minutes after each concentration of provocation agent administrated into the nostrils	Yes
Primary	Percentage of participants positive response to leukotriene D4 or histamine nasal provocation test	Nasal airway resistance measured by positive anterior rhinomanometry. Concentration induced 60% increase of nasal airway resistance (PC60-NAR) will be measured and reported; Composite symptoms score defined by reichmann H and his colleagues showed as follows:3-5 sneezes = 1 point (pt), >5 sneezes = 2 points (pts); rhinorrhoea < 1 milliliter (mL) = 1 pt, rhinorrhoea > 1 milliliter = 2 pts; pruritus of the palate or ear or eye= 1 pt, conjunctivitis or cough or urticaria or difficult breathing= 2 pts. Total score ranges from 0 to 6 pts. Positive response to LTD4 nasal provocation test was defined as PC60-NAR less than 16mcg/mL or the symptom score higher than 3.	Until 1 hour after the nasal provocation test	Yes
Secondary	Change from baseline of eosinophils in sputum and nasal lavage and fractional exhaled nitric oxide (FeNO)	Biomarkers in upper and lower airways such as eosinophils in sputum and nasal lavage and fractional exhaled nitric oxide (FeNO) will be studied.	4 and 24 hours after the nasal provocation test	No