Leukotriene D4 Nasal Provocation Test in Allergic Rhinitis

NCT01963741 | Completed

• 1 other identifier: LTD4NAPT201218
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Allergic Rhinitis; Asthma

Keywords

Leukotriene D4; allergic rhinitis; nasal airway resistance; nasal provocation test; nasal hyperreactivity; airway inflammation; asthma

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (1)

• Change from baseline of eosinophils in sputum and nasal lavage and fractional exhaled nitric oxide (FeNO)

  4 and 24 hours after the nasal provocation test

Other Outcomes (2)

• Change from baseline 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

• Peak Nasal Inspiratory Flow (PNIF)

  3 minutes after each concentration of provocation agent administrated into the nostrils

Study Arms (2)

leukotriene D4

EXPERIMENTAL

Nasal provocation test was induced by leukotriene D4 with a stepwisely concentration method (4 mcg/ml, 8 mcg/ml, 16 mcg/ml).

Drug: histamine

histamine

EXPERIMENTAL

Nasal provocation test was induced by histamine with a stepwisely concentration method (0.4 mg/ml, 0.8 mg/ml, 1.6 mg/ml, 3.2mg/ml).

Drug: leukotriene D4

Interventions

leukotriene D4 DRUG

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.

Also known as: Cayman chemical company (1-800-364-9897 Cat 20310).

histamine

histamine DRUG

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.

Also known as: Guangzhou chemical company (serial number: 1703 )

leukotriene D4

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Guangzhou Institute of Respiratory Disease: lead

Study Sites (1)

Guangzhou institute of respiratory disease

Guangzhou, Guangdong, 510120, China

Location

Related Publications (15)

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

  PMID: 9011329 BACKGROUND

• Howarth PH, Salagean M, Dokic D. Allergic rhinitis: not purely a histamine-related disease. Allergy. 2000;55 Suppl 64:7-16. doi: 10.1034/j.1398-9995.2000.00802.x.

  PMID: 11291780 BACKGROUND

• 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. doi: 10.1016/S1081-1206(10)61018-6.

  PMID: 16400895 BACKGROUND

• 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. doi: 10.2500/aap.2007.28.3000.

  PMID: 17619558 BACKGROUND

• 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. doi: 10.1111/j.1398-9995.2006.01007.x.

  PMID: 16677244 BACKGROUND

• 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. doi: 10.1016/j.anl.2007.06.004. Epub 2007 Sep 7.

  PMID: 17826020 BACKGROUND

• Nayak A, Langdon RB. Montelukast in the treatment of allergic rhinitis: an evidence-based review. Drugs. 2007;67(6):887-901. doi: 10.2165/00003495-200767060-00005.

  PMID: 17428106 BACKGROUND

• Virchow JC, Bachert C. Efficacy and safety of montelukast in adults with asthma and allergic rhinitis. Respir Med. 2006 Nov;100(11):1952-9. doi: 10.1016/j.rmed.2006.02.026. Epub 2006 Apr 12.

  PMID: 16626955 BACKGROUND

• 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. doi: 10.1111/j.1365-2222.1986.tb01960.x.

  PMID: 2427255 BACKGROUND

• 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. doi: 10.1164/ajrccm/136.2.357.

  PMID: 3039881 BACKGROUND

• Brozek JL, Baena-Cagnani CE, Bonini S, Canonica GW, Rasi G, van Wijk RG, Zuberbier T, Guyatt G, Bousquet J, Schunemann HJ. Methodology for development of the Allergic Rhinitis and its Impact on Asthma guideline 2008 update. Allergy. 2008 Jan;63(1):38-46. doi: 10.1111/j.1398-9995.2007.01560.x.

  PMID: 18053015 BACKGROUND

• 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. doi: 10.1055/s-2003-38411. No abstract available. German.

  PMID: 12673517 BACKGROUND

• 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.

  PMID: 23040886 BACKGROUND

• 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.

  PMID: 22435894 BACKGROUND

• Zhu Z, Xie Y, Guan W, Gao YI, Xia S, Liang J, Zheng J. Leukotriene D4 nasal provocation test: Rationale, methodology and diagnostic value. Exp Ther Med. 2016 Jul;12(1):525-529. doi: 10.3892/etm.2016.3324. Epub 2016 May 10.

  PMID: 27347089 DERIVED

MeSH Terms

Conditions

Rhinitis, Allergic; Asthma

Interventions

Leukotriene D4; Histamine

Condition Hierarchy (Ancestors)

Rhinitis; Nose Diseases; Respiratory Tract Diseases; Respiratory Hypersensitivity; Otorhinolaryngologic Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Bronchial Diseases; Lung Diseases, Obstructive; Lung Diseases

Intervention Hierarchy (Ancestors)

SRS-A; Leukotrienes; Arachidonic Acids; Eicosanoids; Fatty Acids, Unsaturated; Fatty Acids; Lipids; Fatty Acids, Essential; Autacoids; Inflammation Mediators; Biological Factors; Biogenic Monoamines; Biogenic Amines; Amines; Organic Chemicals; Ethylamines; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Jinping Zheng, professor

  Guangzhou Institute of Respiratory Disease

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: DIAGNOSTIC
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor,Guangzhou institute of respiratory disease

Study Record Dates

• First Submitted: August 27, 2013
• First Posted: October 16, 2013
• Study Start: November 1, 2012
• Primary Completion: February 1, 2014
• Study Completion: April 1, 2014
• Last Updated: July 9, 2015

Record last verified: 2015-07

Locations

CN (1)