Service d'Endocrinologie et Métabolisme, Assistance Publique - Hôpitaux de Paris, Hôpital de la Pitié-Salpétrière, 75013 Paris, France.
Curr Med Res Opin. 2010 May;26(5):1185-92. doi: 10.1185/03007991003693581.
To investigate the effect of fenofibrate on sleep apnoea indices.
Proof-of-concept study comprising a placebo run-in period (1 week, 5 weeks if fibrate washout was required) and a 4-week randomized, double-blind treatment period. Thirty-four subjects (mean age 55 years, body mass index 34 kg/m 2 , fasting triglycerides 3.5 mmol/L) with diagnosed sleep apnoea syndrome not treated with continuous positive airways pressure were enrolled and randomized to once daily treatment with fenofibrate (145 mg NanoCrystal(R) tablet) or placebo. Overnight polysomnography, computerized attention/vigilance tests and blood sampling for measurement of lipids, insulin, fasting plasma glucose and fibrinogen were performed at the end of each study period.
NCT00816829.
As this was an exploratory study, a range of sleep variables were evaluated. The apnoea/hypopnoea index (AHI) and percentage of time spent with arterial oxygen saturation (SpO(2)) <90% were relevant as they have been evaluated in other clinical trials. Other variables included total apnoeas, hypopnoeas and oxygen desaturations, and non-cortical micro-awakenings related to respiratory events per hour.
Fenofibrate treatment significantly reduced the percentage of time with SpO(2) <90% (from 9.0% to 3.5% vs. 10.0% to 11.5% with placebo, p = 0.007), although there was no significant change in the AHI (reduction vs. control 14% (95%CI -47 to 40%, p = 0.533). Treatment reduced obstructive apnoeas (by 44%, from 18.5 at baseline to 15.0 at end of treatment vs. 29.0 to 30.5 on placebo, p = 0.048), and non-cortical micro-awakenings per hour (from 23.5 to 18.0 vs. 24.0 to 25.0 with placebo, p = 0.004). Other sleep variables were not significantly influenced by fenofibrate.
Exploratory study in patients with mild to moderate sleep apnoea, limited treatment duration; concomitant hypnotic treatment (35%); lack of correction for multiplicity of testing.
The consistent direction of change in sleep indices in this proof-of-concept study may support further investigation of fenofibrate in moderate to severe sleep apnoea syndrome.
研究非诺贝特对睡眠呼吸暂停指数的影响。
这是一项概念验证研究，包括安慰剂导入期（1 周，如果需要洗脱非诺贝特则为 5 周）和为期 4 周的随机、双盲治疗期。纳入了 34 名诊断为睡眠呼吸暂停综合征但未接受持续气道正压通气治疗的患者，他们的平均年龄为 55 岁，体重指数为 34kg/m 2 ，空腹甘油三酯为 3.5mmol/L，随机分为每日一次服用非诺贝特（145mg 纳米晶（R）片）或安慰剂。在每个研究期结束时进行整夜多导睡眠图、计算机注意力/警觉性测试和血液采样，以测量血脂、胰岛素、空腹血糖和纤维蛋白原。
NCT00816829。
由于这是一项探索性研究，评估了一系列睡眠变量。呼吸暂停/低通气指数（AHI）和动脉血氧饱和度（SpO 2 ）<90%的时间百分比是相关的，因为它们在其他临床试验中得到了评估。其他变量包括每小时总呼吸暂停、低通气和氧减饱和度，以及与呼吸事件相关的非皮质微觉醒次数。
非诺贝特治疗组 SpO 2 <90%的时间百分比显著降低（从 9.0%降至 3.5%，安慰剂组从 10.0%降至 11.5%，p=0.007），但 AHI 无显著变化（治疗组与对照组相比降低 14%（95%CI-47 至 40%，p=0.533）。治疗组降低了阻塞性呼吸暂停（从基线时的 18.5 次降至治疗结束时的 15.0 次，安慰剂组从 29.0 次降至 30.5 次，p=0.048），以及每小时非皮质微觉醒次数（从 23.5 次降至 18.0 次，安慰剂组从 24.0 次降至 25.0 次，p=0.004）。非诺贝特对其他睡眠变量没有显著影响。
在轻度至中度睡眠呼吸暂停患者中进行的探索性研究，治疗时间有限；同时使用催眠药物（35%）；未对多重检测进行校正。
这一概念验证研究中睡眠指标的一致变化方向可能支持进一步研究非诺贝特在中度至重度睡眠呼吸暂停综合征中的作用。
