Sputum Matrix Metalloproteinases (MMP) mRNA and Montelukast

• Status: Completed
• Trial end date: 2011-12-01
• Target enrollment: 0
• Participant gender: All

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).

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of East Anglia
• Collaborator: Clinical Research and Trials Unit (Norfolk & Norwich University Hospital, UK)
• Treatments: Montelukast

Criteria

Inclusion Criteria:

• 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.

Exclusion criteria:

• 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