Wheeze and Intermittent Treatment

• Status: Completed
• Trial end date: 2014-02-01
• Target enrollment: 0
• Participant gender: All

Summary

The clinical aim of this trial is to assess whether intermittent montelukast is an effective treatment strategy in preschool wheeze. The mechanisms aim of the trial is to determine whether there is a genetically highly-responsive subgroup of children. In designing this trial the investigators have incorporated several novel aspects. First, parents will be able to adjust the use of oral montelukast to their child's symptoms. This allows the investigators to recruit both "episodic" and "multi trigger" patterns of preschool wheeze - and control for any change in wheeze pattern during the trial. Second, before the investigators issue the trial medication, the investigators will assess children's leukotriene genes, focusing primarily on a gene called ALOX5. This ALOX5 "stratification" step will ensure that an equal number of potentially "treatment-responsive" children receive the active drug (montelukast) and the dummy medicine - and the equal numbers will help the investigators to assess the role of ALOX5. For the trial, the investigators will first recruit 1,300 children with a history of preschool wheeze, then divide them into the group with "responsive" and "less responsive" genes by their ALOX5 status. The investigators will then issue parents with the trial medication; 50% will be given montelukast and 50% will be given dummy medication. Parents will start the trial medication whenever their child develops a cold, and stop the medication when wheeze resolve. Parents will also be able to give the trial medication for wheeze between colds. Over the 12 month trial period, the investigators will assess the number of unscheduled attendances to a medical practitioner for wheeze for each child. At the end of the trial, the investigators will determine whether montelukast is effective then whether there is a difference in response to montelukast between the 2 ALOX5 gene groups.

At the same time, the investigators will measure many other genes that may influence response to montelukast, as well as the amount of leukotrienes that are excreted in the urine before and during attacks. Using these results, the investigators will be able to both inform national treatment policy, and develop new concepts on the mechanism of preschool wheeze that will inform the development of new therapies. Since children will continue to receive "normal" inhaled therapy, there are no ethical issues in giving a dummy medicine to half of the 1300 children to be recruited. The study will be the largest trial in wheezy preschool children to date, and may open up genetic testing in preschool wheeze.

• Phase: Phase 3
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Queen Mary University of London
• Collaborators: University of Aberdeen; University of Leicester
• Treatments: Mannitol; Montelukast

Criteria

Inclusion Criteria:

• age ≥ 10 months and ≤ 5 years old on the day of the first dose of Investigational Medicinal Product

• two or more attacks of parent-reported wheeze

• at least one attack with wheeze validated by a clinician

• the most recent attack within the last 3 months

• contactable by telephone and able to attend one face-to-face review for issue of Investigational Medicinal Product

• parent or guardian able to give written informed consent for their child to participate in the study

Exclusion Criteria:

• any other chronic respiratory condition diagnosed by a clinician including structural airway abnormality (e.g. floppy larynx) and cystic fibrosis

• any chronic condition that increases vulnerability to respiratory tract infection such as severe developmental delay with feeding difficulty

• history of neonatal chronic lung disease

• current continuous oral montelukast therapy

• in a trial using an Investigational Medicinal Product in the previous 3 months prior to recruitment