The effect of GLP-1RA exenatide on idiopathic intracranial hypertension: a randomized clinical trial.
Mitchell, James L Lyons, Hannah S Walker, Jessica K Yiangou, Andreas Grech, Olivia Alimajstorovic, Zerin Greig, Nigel H Li, Yazhou Tsermoulas, Georgios Brock, Kristian
Mitchell, James L
Lyons, Hannah S
Walker, Jessica K
Yiangou, Andreas
Grech, Olivia
Alimajstorovic, Zerin
Greig, Nigel H
Li, Yazhou
Tsermoulas, Georgios
Brock, Kristian
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2023-05-02
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Abstract
Therapeutics to reduce intracranial pressure are an unmet need. Preclinical data have demonstrated a novel strategy to lower intracranial pressure using glucagon-like peptide-1 (GLP-1) receptor signalling. Here, we translate these findings into patients by conducting a randomized, placebo-controlled, double-blind trial to assess the effect of exenatide, a GLP-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 h, 24 h 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 h -5.7 ± 2.9 cmCSF (P = 0.048); 24 h -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. These data provide confidence to proceed to a phase 3 trial in idiopathic intracranial hypertension and highlight the potential to utilize GLP-1 receptor agonist in other conditions characterized by raised intracranial pressure.
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Mitchell JL, Lyons HS, Walker JK, Yiangou A, Grech O, Alimajstorovic Z, Greig NH, Li Y, Tsermoulas G, Brock K, Mollan SP, Sinclair AJ. The effect of GLP-1RA exenatide on idiopathic intracranial hypertension: a randomized clinical trial. Brain. 2023 May 2;146(5):1821-1830. doi: 10.1093/brain/awad003.
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