A Randomized, Double-Blind, and Sham-Controlled Trial of an Innovative Brain-Gut Photobiomodulation Therapy: Safety and Patient Compliance

Background: Recent innovative non-pharmacological interventions and neurostimulation devices have shown potential for application in the treatment of Alzheimer's disease (AD). These include photobiomodulation (PBM) therapy. Objective: This pilot study assesses the safety, compliance with, and efficacy of a brain-gutPBMtherapy for mild-to-moderate AD patients. Methods: This double-blind, randomized, monocentric sham-controlled study started in 2018 and ended prematurely in 2020 due to the COVID-19 pandemic. Fifty-three mild-to-moderate AD patients were randomized, 27 in the PBM group and 26 in the sham group. All patients had 40 treatment sessions lasting 25 min each over 8 weeks and were followed for 4 weeks afterwards. Compliance with the treatment was recorded. Safety was assessed by recording adverse events (AEs), and efficacy was evaluated using neuropsychological tests. Results: The PBM therapy proved to be safe in regard to the number of recorded AEs (44% of the patients), which were balanced between the PBM and sham groups. AEs were mainly mild, and no serious AEs were reported. The majority of the patients (92.5%) were highly compliant, which confirms the feasibility of the PBM treatment. Compared to the sham patients, the PBM patients showed lower ADAS-Cog comprehension sub-scores, higher forward verbal spans, and lower TMT-B execution times, which suggests an improvement in cognitive functions. Conclusion: This study demonstrates the tolerability of and patient compliance with a PBM-based treatment for mild-tomoderate AD patients. It highlights encouraging efficacy trends and provides insights for the design of the next phase trial in a larger AD patient sample.