The Faculty of Population Health Sciences at University College London has initiated a randomised controlled trial to evaluate whether montelukast — an established anti-inflammatory drug used in paediatric asthma — can improve cognitive processing speed in young children with sickle cell anaemia.
Background and rationale
Children with sickle cell disease frequently exhibit cognitive difficulties, particularly reduced processing speed. Researchers link this to the vulnerability of the brain's deep white matter to injury when oxygen saturation falls. Such desaturation can occur at night, often associated with upper-airway obstruction caused by enlarged adenoids and tonsils, and is commonly manifest as snoring.
Trial design and endpoints
The study will randomise children with sickle cell disease to receive montelukast or a comparator/placebo and will use objective measures to assess cognitive change. The primary endpoints are standardised tests of processing speed — the NIH Toolbox and the Cancellation task. Secondary outcomes include magnetic resonance imaging (MRI) of both the adenoids and the brain, alongside validated questionnaires addressing sleep and pain.
| Outcome type | Measures |
|---|---|
| Primary | Processing speed (NIH Toolbox; Cancellation task) |
| Secondary | Brain and adenoid MRI; sleep questionnaires; pain questionnaires |
Why this matters
If montelukast reduces adenoid size and mitigates airway obstruction during sleep, it could plausibly lessen nocturnal hypoxia and thereby protect vulnerable white-matter regions implicated in slowed processing speed. The drug is already in widespread paediatric use for asthma, which could simplify any future translational steps should the trial show benefit.
- Clinical potential: a non-surgical, pharmacological option to address breathing-related contributors to cognitive impairment.
- Research value: objective cognitive testing paired with MRI will clarify mechanisms linking sleep-disordered breathing and brain injury in this population.
- Public-health implication: an effective, well-tolerated intervention could influence routine management of young children with sickle cell disease.
Context and caution
While montelukast's safety profile is well documented in asthma, its effects in children with sickle cell disease and specifically on cognition remain unproven. The trial's combination of cognitive tests and imaging is designed to distinguish symptomatic improvement from measurable neuroanatomical change. Any clinical adoption will require clear evidence of benefit and safety in this distinct patient group.
The study represents a measured attempt to address a pressing concern for families and clinicians: how to prevent or mitigate early cognitive decline in children living with sickle cell disease without immediate recourse to surgery. Results from the trial will be important for clinicians, researchers and policy-makers considering how best to protect neurodevelopment in this vulnerable population.
