Study design of gamma sensory stimulation at multiple dose levels in MCI patients

Abstract

AbstractBackgroundNon‐invasive gamma sensory stimulation has been demonstrated to have beneficial effects on the hallmarks of AD pathophysiology in transgenic mouse models of AD. The Etude clinical trial is a translational clinical study examining dose‐ranging, safety, tolerability, and potential benefits of gamma sensory stimulation as a novel, non‐invasive treatment for Alzheimer’s disease.MethodTwo cohorts were planned to evaluate tolerability, safety and therapeutic effects by dose with results from the first cohort guiding dose escalation for the second. In the first cohort, 10 subjects were randomized to receive once or twice daily therapy for 12 months. When therapy was completed, safety and tolerability, as well as symptom progression, was evaluated and the second cohort was initiated; 3 subjects were enrolled at twice daily 1‐hour therapy for 12 months. All subjects received 40Hz audio‐visual therapy (Cognito Therapeutics, Cambridge MA) at home with assistance from a caregiver. Key criteria for subject enrolment were: adults 50 years and older, MMSE 24‐30, MCI due to AD diagnosis per NIA‐AA criteria, and an amyloid‐positive PET scan. Subjects were excluded for history of seizure, memantine use, alternate causes of cognitive impairment or MRI findings that prevented PET SUVr processing. Subjects were followed for safety, tolerability and changes to symptoms via clinical assessments, phone assessments, and electronic treatment diary. Tolerability was measured by device use, including treatment diary and device‐reported data, Zarit burden interview, and structured interviews at pre‐planned time points. Clinical progression was measured using MMSE, ADAS‐Cog, CDR, NPI, Clock‐Drawing Test, ADL, and QOL. Quantitative EEG, actigraphy, amyloid PET, volumetric MR are evaluated at regular intervals throughout the study as biomarkers.ResultThirty‐seven subjects were screened and 13 enrolled, of whom none terminated early and 3 are still active. An open‐label extension year was added to the protocol and 70% of subjects chose to re‐enroll. Review of MR imaging noted no ARIA and there were no unexpected related serious adverse events. Results on symptomatic and biomarker changes are being analyzed.ConclusionWe describe the design and methods of a translational dosing study which evaluates a novel therapeutic modality. All evaluated dosing regiments were safe and well‐tolerated by subjects.