The effect of GLP-1RA exenatide on idiopathic intracranial hypertension: a randomized clinical trial.
The effect of GLP-1RA exenatide on idiopathic intracranial hypertension: a randomized clinical trial.
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DOI：
10.1093/brain/awad003
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发表时间：
2023-05-02
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降低颅内压的治疗是一种未满足的需求。临床前数据已经证明了一种利用胰高血糖素样肽-1（GLP-1）受体信号传导降低颅内压的新策略。在这里，我们通过进行一项随机、安慰剂对照、双盲试验来评估艾塞那肽（一种GLP-1受体激动剂）对特发性颅内高压患者颅内压的影响，从而将这些发现转化为患者。遥测颅内压导管可实现长期颅内压监测。该试验招募了患有活动性特发性颅内高压（颅内压>25 cmCSF和视乳头水肿）的成年女性，她们接受皮下注射或安慰剂。三个主要结局指标为2.5 h、24 h和12周时的颅内压，先验α集小于0.1。在招募的16名女性中，15名完成了研究（平均年龄28 ± 9岁，体重指数38.1 ± 6.2 kg/m2，颅内压30.6 ± 5.1 cmCSF）。在2.5 h −5.7 ± 2.9 cmCSF（P = 0.048）、24 h −6.4 ± 2.9 cmCSF（P = 0.030）和12周−5.6 ± 3.0 cmCSF（P = 0.058）时，Exenvatinib显著且有意义地降低了颅内压。未观察到严重安全性信号。这些数据为进行特发性颅内高压的3期试验提供了信心，并强调了在以颅内压升高为特征的其他疾病中使用GLP-1受体激动剂的潜力。Mitchell et al.报告称，在一项随机安慰剂对照试验中，GLP-1受体激动剂艾塞那肽可显著降低特发性颅内高压患者的颅内压，包括急性给药和给药12周后。数据支持进入特发性颅内高压的III期试验。
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. Mitchell et al. report that the GLP-1 receptor agonist exenatide significantly reduced intracranial pressure in patients with idiopathic intracranial hypertension, both acutely and after 12 weeks of dosing, in a randomized placebo-controlled trial. The data support moving to a phase 3 trial in idiopathic intracranial hypertension.
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