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Study of montelukast in children with sickle cell disease (SMILES): a study protocol for a randomised controlled
Anna M Hood1, Hanne Stotesbury2, Melanie Kölbel2
1Developmental Neurosciences Unit and Biomedical Research Centre, UCL Great Ormond Street Institute of Child Health, 30 Guilford Street, London, WC1N 1EH, UK. a.hood@ucl.ac.uk.
Insights
This study investigates montelukast for children with sickle cell anaemia (SCA) and sleep-disordered breathing (SDB). It aims to see if the drug improves cognitive function and reduces airway issues, offering a potential new treatment.
Area of Science:
- Pediatric Hematology
- Neurology
- Sleep Medicine
Background:
- Children with sickle cell anaemia (SCA) often experience cognitive deficits, including slowed processing speed, linked to reduced brain white matter integrity, low oxygen saturation, and sleep-disordered breathing (SDB).
- Enlarged adenoids and tonsils contribute to SDB in young children with SCA, with current treatments like adenotonsillectomy and CPAP having limitations.
- Montelukast, an anti-inflammatory agent, has shown efficacy in reducing airway obstruction and adenoid size in children without SCA, but its effects in SCA patients are unknown.
Purpose of the Study:
- To assess the efficacy of montelukast in improving cognitive function, specifically processing speed, in young children with SCA and SDB.
- To evaluate montelukast's impact on sleep quality, adenoid size, and white matter integrity in pediatric SCA patients.
- To determine if montelukast offers a viable alternative treatment for airway obstruction and associated cognitive issues in children with SCA.
Main Methods:
- The Study of Montelukast In Children with Sickle Cell Disease (SMILES) is a 12-week, multicenter, double-blind, randomized controlled trial (RCT).
- 200 pediatric patients with SCA and SDB, aged 3-7.99 years, will be randomized to receive either montelukast or placebo.
- Outcomes will be measured using cognitive evaluations, caregiver questionnaires (sleep, pain), brain MRIs (adenoid size, white matter integrity), and overnight oximetry.
Main Results:
- Primary outcome is the change in processing speed from baseline to post-treatment.
- Secondary outcomes include changes in sleep parameters, adenoid size, and brain white matter integrity.
- Data will be analyzed to compare the effects of montelukast versus placebo on cognitive function and SDB-related markers.
Conclusions:
- Findings will elucidate whether montelukast is an effective treatment for young children with SCA experiencing SDB and cognitive impairments.
- The study aims to provide critical knowledge for developing targeted interventions to improve outcomes in pediatric SCA patients.
- Results may inform clinical practice regarding the use of montelukast as a non-invasive treatment option for SCA-related complications.
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.
Trial Registration:
ClinicalTrials.gov NCT04351698 . Registered on April 17, 2020. European Clinical Trials Database (EudraCT No. 2017-004539-36). Registered on May 19, 2020.
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