Prescribing Asthma Controller Medication According to Gene Status to Improve Quality of Life in Young People With Asthma

NCT02758873 | Completed DMC

• 1 other identifier: 14/054/MUK
• Study Type: interventional
• Target: 241
• Locations: 1 country
• Sites: 5

Brief Summary

One in every 11 children in the United Kingdom (UK) has asthma. Children with asthma cough, wheeze and have difficulty breathing. The symptoms which children experience can mean they miss school and makes it difficult for children to take part in playground games and sports. Some have to be admitted to hospital. In fact, in the UK a child is admitted to hospital every 18 minutes because of their asthma. Effective medicines are available, but a child's response to these medicines is currently unpredictable. This project focuses on an asthma controller medicine called salmeterol. According to reports, tens of thousands of children may be taking this medicine in the UK, but evidence suggests it might not work for around one in seven of them. The study team are investigating whether a new approach to treatment, where prescribing is personalised according to a child's genetic make-up, improves the child's quality of life and provides better control of their asthma. Treatment that is tailored in this way to a person's genetic features is often called 'personalised medicine'. At the moment, doctors commonly prescribe salmeterol to relieve asthma symptoms if children do not benefit enough from other medicines. But evidence suggests salmeterol may not work properly in children with a certain genetic makeup. The study team are investigating whether it helps to take children and young people's genetic makeup into account when deciding whether to give them salmeterol or an alternative medicine called montelukast. A simple and inexpensive saliva test can provide the information needed to guide decision making.

Conditions

Asthma

Outcome Measures

Primary Outcomes (1)

• Asthma Quality of Life Questionnaires with Standardised Activities (AQLQ(S))

  A disease-specific health-related quality of life instrument that taps both physical and emotional impact of disease. Participants are asked to think about how they have been during the previous 2 weeks and to respond to each of the 32 questions on a 7-point scale (7 = not bothered at all - 1 = extremely bothered).

  Past two weeks

Secondary Outcomes (3)

• Asthma Control Questionnaire (ACQ)

  Past week

• Health care utilisation

  3 months

• Medication use

  3 months

Study Arms (2)

Personalised Medicine

EXPERIMENTAL

If an add-on controller is required, young people in this arm will be prescribed personalised medicine by results of the genotyping for the adrenergic beta2-receptor gene (ADRB2). Health professional's will be advised to prescribe inhaled salmeterol as 'add-on' controller if trial participants have the Gly/Gly variant on ADRB2, and montelukast if they have Arg/Arg or Arg/Gly variant on ADRB2.

Genetic: Personalised medicine (Salmeterol); Genetic: Personalised medicine (Montelukast)

Standard care

ACTIVE COMPARATOR

If an add-on controller is required, young people will be prescribed medication as per the choice of the primary or secondary care physician, without knowledge of genotypic status.

Other: Standard care

Interventions

Personalised medicine (Salmeterol) GENETIC

If participants require add-on medication and have the Gly/Gly variant on the ADRB2, salmeterol will be prescribed.

Also known as: Salmeterol

Personalised Medicine

Personalised medicine (Montelukast) GENETIC

If participants require add-on medication and have the Arg/Arg or Arg/Gly variant on the ADRB2, montelukast will be prescribed.

Also known as: Montelukast

Personalised Medicine

Standard care OTHER

If participants require add-on medication in the arm, they will be prescribed either salmeterol or montelukast according to health professional's choice based on current guidelines.

Also known as: Salmeterol or montelukast

Standard care

Eligibility Criteria

• Age: 12 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Parent/Guardian/Participant is willing and able to provide informed consent/assent
• Physician-diagnosed asthma
• Aged 12-18 years
• Taking inhaled corticosteroids (ICS) with/without second line controller (i.e. LABA/LTRA)

You may not qualify if:

• Parent/Guardian/Participant is unwilling or unable to give informed consent/assent
• Known contraindication to montelukast or salmeterol
• Other major airway or lung disease, e.g. chronic lung disease of prematurity, cystic fibrosis, and abnormal airway anatomy
• Pregnant or lactating females (if participants become pregnant during the course of the study they will be asked to inform the research team and be withdrawn from the study)
• Participating in another clinical trial (other than observational trials and registries) concurrently or within 30 days prior to screening for entry into this study
• On step 4 asthma control medication e.g. taking Theophylline, Slo-phylin, Uniphyllin
• Unable to provide saliva/buccal cells for genotyping

Sponsors & Collaborators

• University of Sussex: lead

Study Sites (5)

Brighton & Sussex University Hospitals NHS Trust

Brighton, East Sussex, BN2 5BE, United Kingdom

Location

Kent, Surrey & Sussex CCGs

Gillingham, Kent, ME8 0NZ, United Kingdom

Location

NHS Grampian

Aberdeen, AB25 2ZG, United Kingdom

Location

NHS Tayside

Dundee, DD1 9SY, United Kingdom

Location

Bart's Health NHS Trust

London, NW1 0PE, United Kingdom

Location

Related Publications (13)

• Fuhlbrigge AL, Adams RJ, Guilbert TW, Grant E, Lozano P, Janson SL, Martinez F, Weiss KB, Weiss ST. The burden of asthma in the United States: level and distribution are dependent on interpretation of the national asthma education and prevention program guidelines. Am J Respir Crit Care Med. 2002 Oct 15;166(8):1044-9. doi: 10.1164/rccm.2107057.

  PMID: 12379546 BACKGROUND

• Juniper EF, Guyatt GH, Ferrie PJ, Griffith LE. Measuring quality of life in asthma. Am Rev Respir Dis. 1993 Apr;147(4):832-8. doi: 10.1164/ajrccm/147.4.832.

  PMID: 8466117 BACKGROUND

• Juniper EF, Guyatt GH, Willan A, Griffith LE. Determining a minimal important change in a disease-specific Quality of Life Questionnaire. J Clin Epidemiol. 1994 Jan;47(1):81-7. doi: 10.1016/0895-4356(94)90036-1.

  PMID: 8283197 BACKGROUND

• Basu K, Palmer CN, Tavendale R, Lipworth BJ, Mukhopadhyay S. Adrenergic beta(2)-receptor genotype predisposes to exacerbations in steroid-treated asthmatic patients taking frequent albuterol or salmeterol. J Allergy Clin Immunol. 2009 Dec;124(6):1188-94.e3. doi: 10.1016/j.jaci.2009.07.043.

  PMID: 19800676 BACKGROUND

• Palmer CN, Lipworth BJ, Lee S, Ismail T, Macgregor DF, Mukhopadhyay S. Arginine-16 beta2 adrenoceptor genotype predisposes to exacerbations in young asthmatics taking regular salmeterol. Thorax. 2006 Nov;61(11):940-4. doi: 10.1136/thx.2006.059386. Epub 2006 Jun 13.

  PMID: 16772309 BACKGROUND

• Joos S, Miksch A, Szecsenyi J, Wieseler B, Grouven U, Kaiser T, Schneider A. Montelukast as add-on therapy to inhaled corticosteroids in the treatment of mild to moderate asthma: a systematic review. Thorax. 2008 May;63(5):453-62. doi: 10.1136/thx.2007.081596.

  PMID: 18443162 BACKGROUND

• Liggett SB. The pharmacogenetics of beta2-adrenergic receptors: relevance to asthma. J Allergy Clin Immunol. 2000 Feb;105(2 Pt 2):S487-92. doi: 10.1016/s0091-6749(00)90048-4.

  PMID: 10669529 BACKGROUND

• Lipworth BJ, Basu K, Donald HP, Tavendale R, Macgregor DF, Ogston SA, Palmer CN, Mukhopadhyay S. Tailored second-line therapy in asthmatic children with the Arg(16) genotype. Clin Sci (Lond). 2013 Apr;124(8):521-8. doi: 10.1042/CS20120528.

  PMID: 23126384 BACKGROUND

• Juniper EF, O'Byrne PM, Guyatt GH, Ferrie PJ, King DR. Development and validation of a questionnaire to measure asthma control. Eur Respir J. 1999 Oct;14(4):902-7. doi: 10.1034/j.1399-3003.1999.14d29.x.

  PMID: 10573240 BACKGROUND

• British Thoracic Society; Scottish Intercollegiate Guidelines Network. British guideline on the management of asthma. Thorax. 2003 Feb;58 Suppl 1(Suppl 1):i1-94. doi: 10.1136/thorax.58.suppl_1.1i. No abstract available.

  PMID: 12653493 BACKGROUND

• Lemanske RF Jr, Mauger DT, Sorkness CA, Jackson DJ, Boehmer SJ, Martinez FD, Strunk RC, Szefler SJ, Zeiger RS, Bacharier LB, Covar RA, Guilbert TW, Larsen G, Morgan WJ, Moss MH, Spahn JD, Taussig LM; Childhood Asthma Research and Education (CARE) Network of the National Heart, Lung, and Blood Institute. Step-up therapy for children with uncontrolled asthma receiving inhaled corticosteroids. N Engl J Med. 2010 Mar 18;362(11):975-85. doi: 10.1056/NEJMoa1001278. Epub 2010 Mar 2.

  PMID: 20197425 BACKGROUND

• Juniper EF, Svensson K, Mork AC, Stahl E. Modification of the asthma quality of life questionnaire (standardised) for patients 12 years and older. Health Qual Life Outcomes. 2005 Sep 16;3:58. doi: 10.1186/1477-7525-3-58.

  PMID: 16168050 BACKGROUND

• Ruffles T, Jones CJ, Palmer C, Turner S, Grigg J, Tavendale R, Hogarth F, Rauchhaus P, Pilvinyte K, Hannah R, Smith H, Littleford R, Lipworth B, Mukhopadhyay S. Asthma prescribing according to Arg16Gly beta-2 genotype: a randomised trial in adolescents. Eur Respir J. 2021 Aug 19;58(2):2004107. doi: 10.1183/13993003.04107-2020. Print 2021 Aug.

  PMID: 33479111 DERIVED

Related Links

• Asthma UK

MeSH Terms

Conditions

Asthma

Interventions

Salmeterol Xinafoate; montelukast; Standard of Care

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Albuterol; Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Phenethylamines; Ethylamines; Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Somnath Mukhopadhyay, FRCPCH

  Brighton and Sussex University Hospitals NHS Trust

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 20, 2016
• First Posted: May 3, 2016
• Study Start: February 1, 2016
• Primary Completion: July 1, 2019
• Study Completion: July 1, 2019
• Last Updated: April 16, 2020

Record last verified: 2020-04

Locations

GB (5)