METHODS: Participants were 10-21 years of age with mild/moderate CD or UC and fecal calprotectin (FC) > 200 ug/g within 4 weeks of study entry. Subjects were randomized to receive either ta-VNS targeting the cymba conchae of the external left ear, or sham stimulation, of 5 min duration once daily for a 2-week period, followed by a cross over to the alternative stimulation for an additional 2 weeks. At week 4, all subjects received ta-VNS of 5 min duration twice daily until week 16. Primary study endpoints were clinical remission, and a ≥ 50% reduction in FC level from baseline to week 16. Heart rate variability measurements and patient-reported outcome questionnaires were completed during interval and week 16 assessments.
RESULTS: Twenty-two subjects were enrolled and analyzed (10 CD, 12 UC). Six of 10 with CD had a wPCDAI > 12.5 and 6/12 with UC had a PUCAI > 10 at baseline, correlating to mild to moderate symptom activity. Among the 12 subjects with active symptomatic disease indices at baseline, clinical remission was achieved in 3/6 (50%) with CD and 2/6 (33%) with UC at week 16. Despite all subjects having FC levels ≥ 200 within 4 weeks of enrollment, five subjects (4 UC, 1 CD) had FC levels < 200 at the baseline visit and were excluded from the FC analysis. Of the remaining 17, median baseline FC was 907 µg/g (IQR 411-2,120). At week 16, 11/17 (64.7%) of those with baseline FC ≥ 200 had a ≥ 50% reduction in FC (95% CI 38.3-85.8). In the UC subjects, there was an 81% median reduction in FC vs baseline (833 µg/g; p = 0.03) while in the CD subjects, median reduction in FC at 16 weeks was 51% (357 µg/g; p = 0.09). There were no safety concerns.
CONCLUSIONS: Noninvasive ta-VNS attenuated signs and symptoms in a pediatric cohort with mild to moderate inflammatory bowel disease.
BACKGROUND: NCT03863704-Date of registration 3/4/2019.
方法:参与者年龄为10-21岁,轻度/中度CD或UC,粪便钙卫蛋白(FC)在研究进入4周内>200ug/g。受试者随机接受针对左耳外耳cymba的ta-VNS,或者假刺激,持续5分钟,每天一次,持续2周,然后交叉到另一种刺激,再进行2周。在第4周,所有受试者每天两次接受5分钟持续时间的ta-VNS,直到第16周。主要研究终点是临床缓解,从基线到第16周,FC水平降低≥50%。在间隔和第16周评估期间完成心率变异性测量和患者报告的结果问卷。
结果:登记并分析了22名受试者(10CD,12UC)。CD的10人中有6人的wPCDAI>12.5,UC的6/12在基线时的PUCAI>10,与轻度至中度症状活动相关。在基线时具有活动性症状疾病指数的12名受试者中,在第16周时,CD组3/6(50%)和UC组2/6(33%)的临床缓解.尽管所有受试者在入组后4周内的FC水平≥200,五个受试者(4个UC,1CD)在基线访视时FC水平<200,被排除在FC分析之外。在其余17例中,基线FC中位数为907µg/g(IQR411-2,120)。在第16周,基线FC≥200的患者中有11/17(64.7%)的FC降低≥50%(95%CI38.3-85.8)。在UC科目中,与基线相比,FC的中位数降低了81%(833µg/g;p=0.03),而在CD受试者中,16周时FC的中位降低为51%(357µg/g;p=0.09).没有安全问题。
结论:非侵入性ta-VNS在患有轻度至中度炎症性肠病的儿科队列中减轻了体征和症状。
背景:NCT03863704-注册日期2019年3月4日。