NCT00947453

Brief Summary

Matrix metalloproteinases (MMPs) are a group of 24 zinc containing enzymes in man. These enzymes were originally described as cleaving extracellular matrix (ECM) substrates with a predominant role in ECM homeostasis, but it is now clear that they have much wider functionality. An imbalance between MMP activity and that of their inhibitors (tissue inhibitors of metalloproteinases, TIMPs) is considered to play a critical role in the synthesis or degradation of the extracellular matrix of the airway architecture which results in fixed airflow obstruction in both asthma and chronic obstructive pulmonary disease (COPD). Using quantitative real time polymerase chain reaction (RT-PCR) the investigators have identified a difference between the level of steady state mRNA for MMP-9, MMP-14 and MMP-2 in 2 patients with asthma compared to 4 healthy controls using our method. However the investigators require further refinement of the process in order to optimise RNA quality and to evaluate the effect of montelukast across the entire family of MMPs and their inhibitors (TIMPs).

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
15

participants targeted

Target at below P25 for phase_2 asthma

Timeline
Completed

Started Jul 2009

Typical duration for phase_2 asthma

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

July 1, 2009

Completed
23 days until next milestone

First Submitted

Initial submission to the registry

July 24, 2009

Completed
4 days until next milestone

First Posted

Study publicly available on registry

July 28, 2009

Completed
2.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2011

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2011

Completed
Last Updated

August 23, 2012

Status Verified

August 1, 2012

Enrollment Period

2.4 years

First QC Date

July 24, 2009

Last Update Submit

August 22, 2012

Conditions

Asthma

Keywords

asthmamontelukast

Outcome Measures

Primary Outcomes (1)

  • Primary endpoint is the MMP and TIMP mRNA profile relative to a housekeeping gene

    8 weeks

Secondary Outcomes (3)

  • The difference between treatment with montelukast for 8 weeks and placebo for mRNA for MMP and TIMP

    8 weeks

  • The difference between treatment with montelukast for 8 weeks and placebo for Spirometry - FEV1, FVC, FEV1/FVC ratio

    8 weeks

  • The difference between treatment with montelukast for 8 weeks and placebo for Induced sputum differential cell count

    8 weeks

Study Arms (1)

montelukast group

EXPERIMENTAL

Identified patients with asthma to recieve Montelukast 10 mg (Merck Sharp \& Dohme Ltd, Herts, UK) at 0800 am once daily for 8 weeks.

Drug: montelukast

Interventions

montelukastDRUG

montelukast 10 mg once daily for 8 weeks

montelukast group

Eligibility Criteria

Age18 Years - 60 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64)

You may qualify if:

  • Male or female, aged 18 to 60 years.
  • Diagnosed with asthma, defined as episodic chest tightness, wheezing and dyspnoea, cough.
  • Non-Smoker or Ex-Smoker for at least 10 years and a smoking history of less than 5 pack years.
  • History of asthma symptoms for more than 10years.
  • Receiving as required short acting bronchodilators.
  • Post bronchodilator FEV1 50 to 100 % predicted
  • Evidence of airway calibre reversibility within the previous 12 months: reversibility to salbutamol of 12% following 400mcg inhaled salbutamol, histamine PC20 \< 8mg/ml, diurnal variation in peak expiratory flow of 20%.
  • Able to produce sputum after induction with saline.

You may not qualify if:

  • Cardiac or pulmonary disease other than asthma.
  • Respiratory infection defined as fever, nasal/sinus congestion, fatigue, cough, antibiotic use or yellow/green sputum within 4 weeks prior to study.
  • Receiving inhaled or oral corticosteroid therapy, long acting Beta2 agonist therapy or leukotriene modifying therapy for the previous 1 month.
  • Severe or uncontrolled co-morbid disease.
  • Pregnancy or breastfeeding.
  • Unable to give written informed consent

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University of East Anglia

Norwich, Norfolk, NR47TJ, United Kingdom

Location

Related Publications (14)

  • Cauwe B, Van den Steen PE, Opdenakker G. The biochemical, biological, and pathological kaleidoscope of cell surface substrates processed by matrix metalloproteinases. Crit Rev Biochem Mol Biol. 2007 May-Jun;42(3):113-85. doi: 10.1080/10409230701340019.

    PMID: 17562450BACKGROUND

  • Suzuki R, Miyazaki Y, Takagi K, Torii K, Taniguchi H. Matrix metalloproteinases in the pathogenesis of asthma and COPD: implications for therapy. Treat Respir Med. 2004;3(1):17-27. doi: 10.2165/00151829-200403010-00003.

    PMID: 15174890BACKGROUND

  • Atkinson JJ, Senior RM. Matrix metalloproteinase-9 in lung remodeling. Am J Respir Cell Mol Biol. 2003 Jan;28(1):12-24. doi: 10.1165/rcmb.2002-0166TR.

    PMID: 12495928BACKGROUND

  • Kelly EA, Busse WW, Jarjour NN. Increased matrix metalloproteinase-9 in the airway after allergen challenge. Am J Respir Crit Care Med. 2000 Sep;162(3 Pt 1):1157-61. doi: 10.1164/ajrccm.162.3.9908016.

    PMID: 10988146BACKGROUND

  • Boulay ME, Prince P, Deschesnes F, Chakir J, Boulet LP. Metalloproteinase-9 in induced sputum correlates with the severity of the late allergen-induced asthmatic response. Respiration. 2004 May-Jun;71(3):216-24. doi: 10.1159/000077418.

    PMID: 15133340BACKGROUND

  • Beeh KM, Beier J, Kornmann O, Buhl R. Sputum matrix metalloproteinase-9, tissue inhibitor of metalloprotinease-1, and their molar ratio in patients with chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis and healthy subjects. Respir Med. 2003 Jun;97(6):634-9. doi: 10.1053/rmed.2003.1493.

    PMID: 12814147BACKGROUND

  • Vignola AM, Riccobono L, Mirabella A, Profita M, Chanez P, Bellia V, Mautino G, D'accardi P, Bousquet J, Bonsignore G. Sputum metalloproteinase-9/tissue inhibitor of metalloproteinase-1 ratio correlates with airflow obstruction in asthma and chronic bronchitis. Am J Respir Crit Care Med. 1998 Dec;158(6):1945-50. doi: 10.1164/ajrccm.158.6.9803014.

    PMID: 9847290BACKGROUND

  • Barnes PJ, Hansel TT. Prospects for new drugs for chronic obstructive pulmonary disease. Lancet. 2004 Sep 11-17;364(9438):985-96. doi: 10.1016/S0140-6736(04)17025-6.

    PMID: 15364192BACKGROUND

  • Langlois A, Ferland C, Tremblay GM, Laviolette M. Montelukast regulates eosinophil protease activity through a leukotriene-independent mechanism. J Allergy Clin Immunol. 2006 Jul;118(1):113-9. doi: 10.1016/j.jaci.2006.03.010. Epub 2006 May 19.

    PMID: 16815146BACKGROUND

  • Vignola AM, Riccobono L, Profita M, Foresi A, Di Giorgi R, Guerrera D, Gjomarkaj M, Di Blasi P, Paggiaro PL. Effects of low doses of inhaled fluticasone propionate on inflammation and remodelling in persistent-mild asthma. Allergy. 2005 Dec;60(12):1511-7. doi: 10.1111/j.1398-9995.2005.00827.x.

    PMID: 16266383BACKGROUND

  • Chuang SS, Hung CH, Hua YM, Tien CH, Yang KD, Jong YJ, Hsu SH, Lin CS. Suppression of plasma matrix metalloproteinase-9 following montelukast treatment in childhood asthma. Pediatr Int. 2007 Dec;49(6):918-22. doi: 10.1111/j.1442-200X.2007.02497.x.

    PMID: 18045297BACKGROUND

  • Kevorkian L, Young DA, Darrah C, Donell ST, Shepstone L, Porter S, Brockbank SM, Edwards DR, Parker AE, Clark IM. Expression profiling of metalloproteinases and their inhibitors in cartilage. Arthritis Rheum. 2004 Jan;50(1):131-41. doi: 10.1002/art.11433.

    PMID: 14730609BACKGROUND

  • Standardization of spirometry--1987 update. Statement of the American Thoracic Society. Am Rev Respir Dis. 1987 Nov;136(5):1285-98. doi: 10.1164/ajrccm/136.5.1285. No abstract available.

    PMID: 3674589BACKGROUND

  • Pizzichini E, Pizzichini MM, Efthimiadis A, Evans S, Morris MM, Squillace D, Gleich GJ, Dolovich J, Hargreave FE. Indices of airway inflammation in induced sputum: reproducibility and validity of cell and fluid-phase measurements. Am J Respir Crit Care Med. 1996 Aug;154(2 Pt 1):308-17. doi: 10.1164/ajrccm.154.2.8756799.

    PMID: 8756799BACKGROUND

MeSH Terms

Conditions

Asthma

Interventions

montelukast

Condition Hierarchy (Ancestors)

Bronchial DiseasesRespiratory Tract DiseasesLung Diseases, ObstructiveLung DiseasesRespiratory HypersensitivityHypersensitivity, ImmediateHypersensitivityImmune System Diseases

Study Officials

  • Andrew M Wilson, MRCP (UK)

    University of East Anglia

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER

Study Record Dates

First Submitted

July 24, 2009

First Posted

July 28, 2009

Study Start

July 1, 2009

Primary Completion

December 1, 2011

Study Completion

December 1, 2011

Last Updated

August 23, 2012

Record last verified: 2012-08

Locations

GB(1)