Efficacy of digital therapeutic sinCephalea for personalised nutrition versus control for migraine prevention: A 12-week open-label randomised clinical trial

BackgroundLow-glycaemic diet may alleviate migraine; however, individual blood glucose variability can affect efficacy. In this open-label randomised controlled trial in Germany, we assessed whether the digital therapeutic (DTx) sinCephalea, which delivers personalised low-glycaemic nutritional recommendations supported by intermittent continuous glucose monitoring (CGM), reduces migraine frequency compared with a design-matched control application.MethodsThis open-label trial in Germany assessed the DTx sinCephalea for migraine prevention. Adults aged 18-65 years with episodic migraine were randomised 1:1 (in addition to standard treatment) to the digital therapeutic (intervention) or a design-matched control application. Patients completed a daily headache and medication diary, and 4-weekly patient-reported outcome questionnaires. Adherence to nutritional recommendations was monitored. Primary endpoint (Week 12): change from baseline in monthly migraine days (every 4 weeks) for intervention versus control. Secondary endpoints: change from baseline in monthly migraine days in patients with ≥50% adherence to nutritional recommendations, 30% response rates, migraine- and headache-related impairment, quality-of-life, and acute medication use for intervention versus control. Adverse events were recorded.Results842 patients were randomised between July 2021 and August 2023 (full analysis set: intervention = 416; control = 419). There were significantly greater reductions in monthly migraine days at week 12 for intervention versus control (mean [SD] change: 1.7 [3.4] versus 1.2 [3.2] days; between-group difference estimate: -0.53 [95% CI -0.98 to -0.09]; p = 0.0195) with similar monthly migraine days reductions observed in adherent patients (p = 0.0062; adjusted α = 0.05). Response rate was 54.9% (185/337) in intervention versus 42.9% (168/392) in control (odds ratio: 1.63 [95% CI 1.21-2.19]; p = 0.0012; adjusted α = 0.0125). Migraine- and headache-related impairment were lower at week 12 for intervention versus control (p = 0.0247, adjusted α = 0.0167and p = 0.0001, adjusted α = 0.01, respectively). There was no significant difference in quality-of-life or acute medication use and no digital therapeutic-related adverse events.ConclusionPersonalised nutrition, supported by intermittent CGM, via the DTx sinCephalea, was efficacious for migraine prevention without DTx-related adverse events. This study provides evidence in support of the link between diet and migraine frequency and symptoms. Additionally, as this is a non-pharmacological treatment with no DTx-related side effects, it may be an attractive option for patients. DTx could also reduce the burden of migraine on healthcare systems by providing a scalable, remote, non-invasive and convenient treatment option.