Kennedy Center for Research on Human Development, Vanderbilt University, Nashville, Tennessee, USA.
Division of Pediatric Endocrinology, University of Florida, College of Medicine, Gainesville, Florida, USA.
JCI Insight. 2018 Jun 21;3(12). doi: 10.1172/jci.insight.98333.
Prader-Willi syndrome (PWS) is a genetic neurodevelopmental disorder of life-threatening hyperphagia, obesity, intellectual deficits, compulsivity, and other behavioral problems. The efficacy and safety of i.n. carbetocin, an oxytocin analog, was evaluated in a prospective, randomized, double-blinded trial in adolescents with PWS.
Eligible patients aged 10-18 years with genetically confirmed PWS were randomized (1:1) to i.n. carbetocin or placebo 3 times daily for 14 days. The primary efficacy endpoint was change in parent/caregiver-rated Hyperphagia in PWS Questionnaire-Responsiveness (HPWSQ-R) total score. Secondary efficacy endpoints included HPWSQ-R behavior, drive, and severity domains; clinician-rated HPWSQ; Children's Yale-Brown Obsessive-Compulsive Severity Scale; food domain of the Reiss Profile; and Clinical Global Impression-Improvement scale. Endpoints were assessed using analysis of covariance. Relationship between primary and secondary endpoints was assessed using Pearson correlation coefficients. Safety was assessed throughout the study.
Demographics and clinical characteristics were similar between treatment groups (carbetocin, n = 17; placebo, n = 20). Patients receiving carbetocin had statistically significant reductions in HPWSQ-R total score at study end (-15.6) versus patients receiving placebo (-8.9; P = 0.029); several secondary efficacy endpoints also demonstrated significant differences (P < 0.05). Treatment effects for the primary and secondary endpoints were highly correlated (P ≤ 0.0001). Incidence of adverse events (AEs) was similar between treatment groups.
I.n. carbetocin was well tolerated and improved hyperphagia and behavioral symptoms of PWS.
ClinicalTrials.gov: NCT01968187FUNDING. The study was funded by Ferring Pharmaceuticals. Recruitment was aided by ongoing work in PWS performed through Eunice Kennedy Shriver National Institute of Child Health and Human Development grant U54 HD083211.
普拉德-威利综合征（PWS）是一种危及生命的过度摄食、肥胖、智力缺陷、强迫性和其他行为问题的遗传神经发育障碍。在一项针对患有 PWS 的青少年的前瞻性、随机、双盲试验中，评估了鼻内给予催产素类似物卡贝缩宫素的疗效和安全性。
年龄在 10-18 岁、经基因证实患有 PWS 的合格患者被随机（1:1）分为鼻内给予卡贝缩宫素或安慰剂，每日 3 次，持续 14 天。主要疗效终点是父母/照顾者评定的 PWS 问卷反应性（HPWSQ-R）总分的变化。次要疗效终点包括 HPWSQ-R 行为、驱动和严重程度域；临床医生评定的 HPWSQ；儿童耶鲁-布朗强迫症严重程度量表；Reiss 特征的食物域；和临床总体印象-改善量表。终点采用协方差分析进行评估。主要和次要终点之间的关系采用 Pearson 相关系数进行评估。整个研究过程中评估安全性。
治疗组之间的人口统计学和临床特征相似（卡贝缩宫素组，n = 17；安慰剂组，n = 20）。接受卡贝缩宫素治疗的患者在研究结束时 HPWSQ-R 总分有统计学意义的降低（-15.6），而接受安慰剂治疗的患者则降低了（-8.9；P = 0.029）；几个次要疗效终点也显示出显著差异（P < 0.05）。主要和次要终点的治疗效果高度相关（P ≤ 0.0001）。治疗组之间不良反应（AE）的发生率相似。
鼻内给予卡贝缩宫素耐受性良好，可改善 PWS 的过度摄食和行为症状。
ClinicalTrials.gov：NCT01968187。该研究由 Ferring 制药公司资助。通过 Eunice Kennedy Shriver 国立儿童健康与人类发育研究所授予的 U54HD083211 号正在进行的 PWS 工作，协助了招募工作。
