Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Wheeze and Intermittent Treatment (WAIT)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01142505
Recruitment Status : Completed
First Posted : June 11, 2010
Last Update Posted : April 29, 2014
Sponsor:
Collaborators:
University of Aberdeen
University of Leicester
Information provided by (Responsible Party):
Jonathan Grigg, Queen Mary University of London

Brief 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.


Condition or disease Intervention/treatment Phase
Wheezing Drug: Mannitol Drug: Montelukast Phase 3

Show Show detailed description

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1358 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Parent-determined Oral Montelukast Therapy for Preschool Wheeze With Stratification for Arachidonate-5-Lipoxygenase (ALOX5) Promoter Genotype
Study Start Date : November 2010
Actual Primary Completion Date : February 2014
Actual Study Completion Date : February 2014

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Placebo Comparator: Placebo
Patients in the placebo arm will be given an inactive version of the investigational medical product formed of the excipient mannitol (which is coated with the active drug montelukast in the active comparator arm)
Drug: Mannitol
4mg once daily granules for 10 days, given orally alone or with cold or warm food from the onset of a cold or wheezing attack.
Other Name: Pearlitol SD 200

Active Comparator: Montelukast
Patients in the active arm will be given an active version of the investigational medical product formed of the inactive excipient mannitol with a coating of active drug montelukast.
Drug: Montelukast
4mg once daily granules for 10 days, given orally alone or with cold or warm food from the onset of a cold or wheezing attack
Other Name: Singulair




Primary Outcome Measures :
  1. Need for unscheduled medical attention [ Time Frame: 12 months ]
    Number of times a child attends for an unscheduled medical opinion with respiratory problems over a 12 month period, as confirmed from medical records.


Secondary Outcome Measures :
  1. Number of admissions to hospital [ Time Frame: 12 months ]
  2. Duration of admissions to hospital [ Time Frame: 12 months ]
  3. Number of unscheduled GP consultations for wheeze [ Time Frame: 12 months ]
    The number of times a child is brought to his primary care/family doctor with wheeze

  4. Duration of wheezy episodes [ Time Frame: 12 months ]
    The duration of wheezy episodes as recorded by parents on their diary cards.

  5. Severity of episodes by diary card [ Time Frame: 12 months ]
    The severity of wheeze episodes as recorded in parent diary cards

  6. Parent's overall impression of efficacy of Investigational Medicinal Product [ Time Frame: 12 months ]
    Parent's overall impression of efficacy of Investigational Medicinal Product as recorded in diary cards.

  7. Time to first attack of wheeze [ Time Frame: 12 months ]
    Time to first attack of wheeze as recorded in parent diary card and researcher phonecalls.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   10 Months to 5 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01142505


Locations
Layout table for location information
United Kingdom
Barts and the London NHS Trust
London, United Kingdom, E1 1BB
Sponsors and Collaborators
Queen Mary University of London
University of Aberdeen
University of Leicester
Investigators
Layout table for investigator information
Principal Investigator: Jonathan Grigg, BSc MBBS MD Queen Mary University of London
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Jonathan Grigg, Professor of Paediatric Respiratory Medicine, Queen Mary University of London
ClinicalTrials.gov Identifier: NCT01142505    
Other Study ID Numbers: 08/43/03
2009-015626-11 ( EudraCT Number )
First Posted: June 11, 2010    Key Record Dates
Last Update Posted: April 29, 2014
Last Verified: April 2014
Keywords provided by Jonathan Grigg, Queen Mary University of London:
wheeze
preschool
leukotriene
montelukast
5-lipoxygenase
Additional relevant MeSH terms:
Layout table for MeSH terms
Respiratory Sounds
Signs and Symptoms, Respiratory
Mannitol
Montelukast
Anti-Asthmatic Agents
Respiratory System Agents
Leukotriene Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Cytochrome P-450 CYP1A2 Inducers
Cytochrome P-450 Enzyme Inducers
Molecular Mechanisms of Pharmacological Action
Diuretics, Osmotic
Diuretics
Natriuretic Agents