The effect of GLP-1RA exenatide on Idiopathic Intracranial Hypertension: Randomised Clinical Trial

Abstract

AbstractTherapeutics to reduce intracranial pressure are an unmet need. Pre-clinical data has demonstrated a novel strategy to lower intracranial pressure using glucagon-like peptide-1 receptor signaling.Here, we translate these findings into patients by conducting a randomized, placebo controlled, double-blind trial to assess the effect of exenatide, a glucagon-like peptide-1 receptor agonist, on intracranial pressure in idiopathic intracranial hypertension. Telemetric intracranial pressure catheters enabled long-term intracranial pressure monitoring. The trial enrolled adult women with active idiopathic intracranial hypertension (intracranial pressure >25 cmCSF and papilloedema) who receive subcutaneous exenatide or placebo. The three primary outcome measures were intracranial pressure at 2.5 hours, 24 hours and 12 weeks and alpha set a priori at less than 0.1.Among the 16 women recruited, 15 completed the study (mean age 28 ± 9, body mass index 38.1 ± 6.2 kg/m2, intracranial pressure 30.6 ± 5.1 cmCSF). Exenatide significantly and meaningfully lowered intracranial pressure at 2.5 hours -5.7 ± 2.9 cmCSF (p=0.048); 24 hours of -6.4 ± 2.9 cmCSF (p=0.030); and 12 weeks -5.6 ± 3.0 cmCSF (p=0.058). No serious safety signals were noted.This data provides confidence to proceed to a phase 3 trial in idiopathic intracranial hypertension and highlights the potential to utilise glucagon-like peptide-1 receptor agonist in other conditions characterised by raised intracranial pressure.