Efficacy of digital therapeutic sinCephalea for personalised nutrition versus control for migraine prevention: A 12-week open-label randomised clinical trial
Stefan Evers, Hanna C.B. Grube, Astrid Gendolla, Charly Gaul, Kristian Ewald, Oliver Witt, Jenny Voggel, Matthias Nitschke, Christian Sina, Diamant Thaçi, Inke R. König, Torsten SchröderBackground
Low-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.
Methods
This 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.
Results
842 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.
Conclusion
Personalised 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.