2 IIH Pressure – a randomised, controlled, double blind physiology study of the effect of Exenatide on intracranial pressure

Introduction Raised intracranial pressure (ICP) causes significant morbidity and mortality in a range of conditions including idiopathic intracranial hypertension (IIH) and traumatic brain injury (TBI). Exenatide is a GLP-1 receptor agonist; pre-clinical data demonstrates its ability to reduce ICP. GLP-1R agonists have also been shown to have neuro-protective properties in pre-clinical models of TBI. The objectives of this study are to assess the biological effect of a Glucagon-like Peptide 1 (GLP-1) agonist on ICP in a cohort of participants with IIH, a raised ICP model. Methods Randomised, placebo controlled, double-blind physiology study of Exenatide in women with active IIH (>25 cmCSF lumbar puncture opening pressure and papilloedema). Telemetric, intraparenchymal ICP monitors were implanted to enable gold standard, long-term ICP monitoring (Raumedic p-Tel, Helmbrechts, Germany). Participants were randomised 1:1 to receive Exenatide (10 mcg BD sub-cutaneous) or placebo for 12 weeks. ICP was recorded over a 24-hour baseline visit, at two weeks and 12 weeks. Monthly headache diaries were completed at baseline and 8–12 weeks. Significance was set at p Results Of the 16 participants recruited, 15 were randomised and completed the study: age 29.5 ±9.5 years, BMI 38.1 ±6.2 kg/m2, ICP 30.6±5.1 cmCSF. All ICP monitor implants were well tolerated and allowed successful ICP quantification. A significant reduction in ICP was noted at all timepoints: at 2.5 hours -5.7 cm CSF (p=0.031), at 24 hours -6.3 cmCSF (p=0.095), and at 12 weeks -5.6 cmCSF (p=0.064). Conclusions We report the first human study to assess the biological effect of the GLP-1 agonist Exenatide on ICP in IIH utilising highly accurate implantable telemetric ICP monitors. Exenatide reduced ICP at all timepoints including acutely at 2.5 hrs and during chronic dosing. New therapies for ICP modulation are a significant un-met need in both military and civilian spheres.