PDF(Pubmed)
Abstract：
BACKGROUND: Vagus nerve stimulation is an investigational anti-inflammatory therapy targeting the nervous system to modulate immune activity. This study evaluated the efficacy and safety of transcutaneous auricular VNS (ta-VNS) in patients with pediatric-onset Crohn\'s disease (CD) or ulcerative colitis (UC).
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.
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.
摘要：
背景：迷走神经刺激是一种针对神经系统调节免疫活性的研究性抗炎治疗。这项研究评估了经皮耳廓VNS（ta-VNS）在小儿克罗恩病（CD）或溃疡性结肠炎（UC）患者中的疗效和安全性。
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。
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。
