Aims/hypothesis

Diabetic gastroenteropathy frequently causes debilitating gastrointestinal symptoms. Previous uncontrolled studies have shown that transcutaneous vagal nerve stimulation (tVNS) may improve gastrointestinal symptoms. To investigate the effect of cervical tVNS in individuals with diabetes suffering from autonomic neuropathy and gastrointestinal symptoms, we conducted a randomised, sham-controlled, double-blind (participants and investigators were blinded to the allocated treatment) study.

Methods

This study included adults (aged 20–86) with type 1 or 2 diabetes, gastrointestinal symptoms and autonomic neuropathy recruited from three Steno Diabetes Centres in Denmark. Participants were randomly allocated 1:1 to receive active or sham stimulation. Active cervical tVNS or sham stimulation was self-administered over two successive study periods: 1 week of four daily stimulations and 8 weeks of two daily stimulations. The primary outcome measures were gastrointestinal symptom changes as measured using the gastroparesis cardinal symptom index (GCSI) and the gastrointestinal symptom rating scale (GSRS). Secondary outcomes included gastrointestinal transit times and cardiovascular autonomic function.

Results

Sixty-eight participants were randomised to the active group, while 77 were randomised to the sham group. Sixty-three in the active and 68 in the sham group remained for analysis in study period 1, while 62 in each group were analysed in study period 2. In study period 1, active and sham tVNS resulted in similar symptom reductions (GCSI: −0.26 ± 0.64 vs −0.17 ± 0.62, p=0.44; GSRS: −0.35 ± 0.62 vs −0.32 ± 0.59, p=0.77; mean ± SD). In study period 2, active stimulation also caused a mean symptom decrease that was comparable to that observed after sham stimulation (GCSI: −0.47 ± 0.78 vs −0.33 ± 0.75, p=0.34; GSRS: −0.46 ± 0.90 vs −0.35 ± 0.79, p=0.50). Gastric emptying time was increased in the active group compared with sham (23 min vs −19 min, p=0.04). Segmental intestinal transit times and cardiovascular autonomic measurements did not differ between treatment groups (all p>0.05). The tVNS was well-tolerated.

Conclusions/interpretation

Cervical tVNS, compared with sham stimulation, does not improve gastrointestinal symptoms among individuals with diabetes and autonomic neuropathy.

Trial registration

ClinicalTrials.gov NCT04143269

Funding

The study was funded by the Novo Nordisk Foundation (grant number NNF180C0052045)

Graphical Abstract

中文翻译：

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经皮迷走神经刺激治疗糖尿病患者胃肠道症状：一项随机、双盲、假对照、多中心试验

目标/假设

糖尿病胃肠病经常导致胃肠道症状虚弱。之前的非对照研究表明，经皮迷走神经刺激（tVNS）可以改善胃肠道症状。为了调查颈部 tVNS 对患有自主神经病变和胃肠道症状的糖尿病患者的影响，我们进行了一项随机、假手术对照、双盲（参与者和研究人员对分配的治疗不知情）研究。

方法

这项研究纳入了从丹麦三个 Steno 糖尿病中心招募的患有 1 型或 2 型糖尿病、胃肠道症状和自主神经病变的成年人（20-86 岁）。参与者按照 1:1 的比例随机分配接受主动刺激或假刺激。在两个连续的研究期间自行进行主动颈部 tVNS 或假刺激：1 周每天四次刺激和 8 周每天两次刺激。主要结局指标是使用胃轻瘫主要症状指数（GCSI）和胃肠道症状评定量表（GSRS）测量的胃肠道症状变化。次要结局包括胃肠道传输时间和心血管自主功能。

结果

68 名参与者被随机分配到活性组，77 名参与者被随机分配到假手术组。活动组中的 63 例和假组中的 68 例仍在研究阶段 1 中进行分析，而研究阶段 2 中每组中的 62 例进行了分析。在研究阶段 1 中，活动组和假组 tVNS 导致相似的症状减轻（GCSI：- 0.26 ± 0.64 对比 -0.17 ± 0.62，p = 0.44；GSRS：-0.35 ± 0.62 对比 -0.32 ± 0.59，p = 0.77；平均值±SD）。在研究第 2 期中，主动刺激还导致平均症状减轻，与假刺激后观察到的结果相当（GCSI：-0.47 ± 0.78 与 -0.33 ± 0.75，p = 0.34；GSRS：-0.46 ± 0.90 与 -0.35 ± 0.79 ，p = 0.50）。与假手术组相比，活性组的胃排空时间增加（23 分钟 vs -19 分钟，p = 0.04）。治疗组之间的节段性肠道传输时间和心血管自主测量没有差异（所有p > 0.05）。 tVNS 耐受性良好。

结论/解释

与假刺激相比，颈部 tVNS 不能改善糖尿病和自主神经病变患者的胃肠道症状。

试用注册

临床试验.gov NCT04143269

资金

该研究由诺和诺德基金会资助（资助号 NNF180C0052045）

图形概要