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Study of montelukast in children with sickle cell disease (SMILES): a study protocol for a randomised controlled trial

Study of montelukast in children with sickle cell disease (SMILES): a study protocol for a randomised controlled trial
Study of montelukast in children with sickle cell disease (SMILES): a study protocol for a randomised controlled trial
Background
Young children with sickle cell anaemia (SCA) often have slowed processing speed associated with reduced brain white matter integrity, low oxygen saturation, and sleep-disordered breathing (SDB), related in part to enlarged adenoids and tonsils. Common treatments for SDB include adenotonsillectomy and nocturnal continuous positive airway pressure (CPAP), but adenotonsillectomy is an invasive surgical procedure, and CPAP is rarely well-tolerated. Further, there is no current consensus on the ability of these treatments to improve cognitive function. Several double-blind, randomised controlled trials (RCTs) have demonstrated the efficacy of montelukast, a safe, well-tolerated anti-inflammatory agent, as a treatment for airway obstruction and reducing adenoid size for children who do not have SCA. However, we do not yet know whether montelukast reduces adenoid size and improves cognition function in young children with SCA.

Methods
The Study of Montelukast In Children with Sickle Cell Disease (SMILES) is a 12-week multicentre, double-blind, RCT. SMILES aims to recruit 200 paediatric patients with SCA and SDB aged 3–7.99 years to assess the extent to which montelukast can improve cognitive function (i.e. processing speed) and sleep and reduce adenoidal size and white matter damage compared to placebo. Patients will be randomised to either montelukast or placebo for 12 weeks. The primary objective of the SMILES trial is to assess the effect of montelukast on processing speed in young children with SCA. At baseline and post-treatment, we will administer a cognitive evaluation; caregivers will complete questionnaires (e.g. sleep, pain) and measures of demographics. Laboratory values will be obtained from medical records collected as part of standard care. If a family agrees, patients will undergo brain MRIs for adenoid size and other structural and haemodynamic quantitative measures at baseline and post-treatment, and we will obtain overnight oximetry.

Discussion
Findings from this study will increase our understanding of whether montelukast is an effective treatment for young children with SCA. Using cognitive testing and MRI, the SMILES trial hopes to gain critical knowledge to help develop targeted interventions to improve the outcomes of young children with SCA.
Sickle cell anaemia, Processing speed, Executive function, Sleep-disordered breathing, hypoxia, Randomised control trial
1745-6215
Hood, Anna M.
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Stotesbury, Hanne
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Kolbel, Melanie
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DeHaan, Michelle
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Downes, Michelle
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Kawadler, Jamie M.
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Sahota, Satwinder
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Dimitriou, Dagmara
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Inusa, Baba
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Wilkey, Olu
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Pelidis, Maria
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Trompeter, Sara
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Leigh, Andrea
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Younis, Janine
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Drasar, Emma
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Chakravorty, Subarna
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Rees, David C.
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Height, Sue
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Lawson, Sarah
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Gavlak, Johanna
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Gupta, Atul
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Ridout, Deborah
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Clark, Christopher A.
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Kirkham, Fenella J.
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Hood, Anna M.
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Stotesbury, Hanne
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Kolbel, Melanie
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DeHaan, Michelle
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Downes, Michelle
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Kawadler, Jamie M.
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Sahota, Satwinder
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Dimitriou, Dagmara
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Inusa, Baba
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Wilkey, Olu
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Pelidis, Maria
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Trompeter, Sara
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Leigh, Andrea
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Younis, Janine
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Drasar, Emma
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Chakravorty, Subarna
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Rees, David C.
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Height, Sue
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Lawson, Sarah
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Gavlak, Johanna
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Gupta, Atul
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Ridout, Deborah
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Clark, Christopher A.
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Kirkham, Fenella J.
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Hood, Anna M., Stotesbury, Hanne, Kolbel, Melanie, DeHaan, Michelle, Downes, Michelle, Kawadler, Jamie M., Sahota, Satwinder, Dimitriou, Dagmara, Inusa, Baba, Wilkey, Olu, Pelidis, Maria, Trompeter, Sara, Leigh, Andrea, Younis, Janine, Drasar, Emma, Chakravorty, Subarna, Rees, David C., Height, Sue, Lawson, Sarah, Gavlak, Johanna, Gupta, Atul, Ridout, Deborah, Clark, Christopher A. and Kirkham, Fenella J. (2021) Study of montelukast in children with sickle cell disease (SMILES): a study protocol for a randomised controlled trial. Trials, 22 (1). (doi:10.1186/s13063-021-05626-6).

Record type: Article

Abstract

Background
Young children with sickle cell anaemia (SCA) often have slowed processing speed associated with reduced brain white matter integrity, low oxygen saturation, and sleep-disordered breathing (SDB), related in part to enlarged adenoids and tonsils. Common treatments for SDB include adenotonsillectomy and nocturnal continuous positive airway pressure (CPAP), but adenotonsillectomy is an invasive surgical procedure, and CPAP is rarely well-tolerated. Further, there is no current consensus on the ability of these treatments to improve cognitive function. Several double-blind, randomised controlled trials (RCTs) have demonstrated the efficacy of montelukast, a safe, well-tolerated anti-inflammatory agent, as a treatment for airway obstruction and reducing adenoid size for children who do not have SCA. However, we do not yet know whether montelukast reduces adenoid size and improves cognition function in young children with SCA.

Methods
The Study of Montelukast In Children with Sickle Cell Disease (SMILES) is a 12-week multicentre, double-blind, RCT. SMILES aims to recruit 200 paediatric patients with SCA and SDB aged 3–7.99 years to assess the extent to which montelukast can improve cognitive function (i.e. processing speed) and sleep and reduce adenoidal size and white matter damage compared to placebo. Patients will be randomised to either montelukast or placebo for 12 weeks. The primary objective of the SMILES trial is to assess the effect of montelukast on processing speed in young children with SCA. At baseline and post-treatment, we will administer a cognitive evaluation; caregivers will complete questionnaires (e.g. sleep, pain) and measures of demographics. Laboratory values will be obtained from medical records collected as part of standard care. If a family agrees, patients will undergo brain MRIs for adenoid size and other structural and haemodynamic quantitative measures at baseline and post-treatment, and we will obtain overnight oximetry.

Discussion
Findings from this study will increase our understanding of whether montelukast is an effective treatment for young children with SCA. Using cognitive testing and MRI, the SMILES trial hopes to gain critical knowledge to help develop targeted interventions to improve the outcomes of young children with SCA.

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Accepted/In Press date: 14 September 2021
Published date: 10 October 2021
Keywords: Sickle cell anaemia, Processing speed, Executive function, Sleep-disordered breathing, hypoxia, Randomised control trial

Identifiers

Local EPrints ID: 470224
URI: http://eprints.soton.ac.uk/id/eprint/470224
ISSN: 1745-6215
PURE UUID: d0fa3b99-aa2e-40be-93a7-97e37dfb04bc
ORCID for Fenella J. Kirkham: ORCID iD orcid.org/0000-0002-2443-7958

Catalogue record

Date deposited: 04 Oct 2022 16:51
Last modified: 17 Mar 2024 02:53

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Contributors

Author: Anna M. Hood
Author: Hanne Stotesbury
Author: Melanie Kolbel
Author: Michelle DeHaan
Author: Michelle Downes
Author: Jamie M. Kawadler
Author: Satwinder Sahota
Author: Dagmara Dimitriou
Author: Baba Inusa
Author: Olu Wilkey
Author: Maria Pelidis
Author: Sara Trompeter
Author: Andrea Leigh
Author: Janine Younis
Author: Emma Drasar
Author: Subarna Chakravorty
Author: David C. Rees
Author: Sue Height
Author: Sarah Lawson
Author: Johanna Gavlak
Author: Atul Gupta
Author: Deborah Ridout
Author: Christopher A. Clark

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