PMID- 38515445 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20240323 IS - 1664-2295 (Print) IS - 1664-2295 (Electronic) IS - 1664-2295 (Linking) VI - 15 DP - 2024 TI - Safety, tolerability, and efficacy estimate of evoked gamma oscillation in mild to moderate Alzheimer's disease. PG - 1343588 LID - 10.3389/fneur.2024.1343588 [doi] LID - 1343588 AB - BACKGROUND: Alzheimer's Disease (AD) is a multifactorial, progressive neurodegenerative disease that disrupts synaptic and neuronal activity and network oscillations. It is characterized by neuronal loss, brain atrophy and a decline in cognitive and functional abilities. Cognito's Evoked Gamma Therapy System provides an innovative approach for AD by inducing EEG-verified gamma oscillations through sensory stimulation. Prior research has shown promising disease-modifying effects in experimental AD models. The present study (NCT03556280: OVERTURE) evaluated the feasibly, safety and efficacy of evoked gamma oscillation treatment using Cognito's medical device (CogTx-001) in participants with mild to moderate AD. METHODS: The present study was a randomized, double blind, sham-controlled, 6-months clinical trial in participants with mild to moderate AD. The trial enrolled 76 participants, aged 50 or older, who met the clinical criteria for AD with baseline MMSE scores between 14 and 26. Participants were randomly assigned 2:1 to receive self-administered daily, one-hour, therapy, evoking EEG-verified gamma oscillations or sham treatment. The CogTx-001 device was use at home with the help of a care partner, over 6 months. The primary outcome measures were safety, evaluated by physical and neurological exams and monthly assessments of adverse events (AEs) and MRI, and tolerability, measured by device use. Although the trial was not statistically powered to evaluate potential efficacy outcomes, primary and secondary clinical outcome measures included several cognitive and functional endpoints. RESULTS: Total AEs were similar between groups, there were no unexpected serious treatment related AEs, and no serious treatment-emergent AEs that led to study discontinuation. MRI did not show Amyloid-Related Imaging Abnormalities (ARIA) in any study participant. High adherence rates (85-90%) were observed in sham and treatment participants. There was no statistical separation between active and sham arm participants in primary outcome measure of MADCOMS or secondary outcome measure of CDR-SB or ADAS-Cog14. However, some secondary outcome measures including ADCS-ADL, MMSE, and MRI whole brain volume demonstrated reduced progression in active compared to sham treated participants, that achieved nominal significance. CONCLUSION: Our results demonstrate that 1-h daily treatment with Cognito's Evoked Gamma Therapy System (CogTx-001) was safe and well-tolerated and demonstrated potential clinical benefits in mild to moderate AD.Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT03556280. CI - Copyright (c) 2024 Hajos, Boasso, Hempel, Shpokayte, Konisky, Seshagiri, Fomenko, Kwan, Nicodemus-Johnson, Hendrix, Vaughan, Kern, Megerian and Malchano. FAU - Hajos, Mihaly AU - Hajos M AD - Cognito Therapeutics, Inc., Cambridge, MA, United States. AD - Department of Comparative Medicine, Yale University School of Medicine, New Haven, CT, United States. FAU - Boasso, Alyssa AU - Boasso A AD - Cognito Therapeutics, Inc., Cambridge, MA, United States. FAU - Hempel, Evan AU - Hempel E AD - Cognito Therapeutics, Inc., Cambridge, MA, United States. FAU - Shpokayte, Monika AU - Shpokayte M AD - Cognito Therapeutics, Inc., Cambridge, MA, United States. FAU - Konisky, Alex AU - Konisky A AD - Cognito Therapeutics, Inc., Cambridge, MA, United States. FAU - Seshagiri, Chandran V AU - Seshagiri CV AD - Cognito Therapeutics, Inc., Cambridge, MA, United States. FAU - Fomenko, Vitella AU - Fomenko V AD - Cognito Therapeutics, Inc., Cambridge, MA, United States. FAU - Kwan, Kim AU - Kwan K AD - Cognito Therapeutics, Inc., Cambridge, MA, United States. FAU - Nicodemus-Johnson, Jessie AU - Nicodemus-Johnson J AD - Pentara Corporation, Millcreek, UT, United States. FAU - Hendrix, Suzanne AU - Hendrix S AD - Pentara Corporation, Millcreek, UT, United States. FAU - Vaughan, Brent AU - Vaughan B AD - Cognito Therapeutics, Inc., Cambridge, MA, United States. FAU - Kern, Ralph AU - Kern R AD - Cognito Therapeutics, Inc., Cambridge, MA, United States. FAU - Megerian, Jonathan T AU - Megerian JT AD - Thompson Autism Center, CHOC Children's, Orange, CA, United States. FAU - Malchano, Zach AU - Malchano Z AD - Cognito Therapeutics, Inc., Cambridge, MA, United States. LA - eng SI - ClinicalTrials.gov/NCT03556280 PT - Journal Article DEP - 20240306 PL - Switzerland TA - Front Neurol JT - Frontiers in neurology JID - 101546899 PMC - PMC10957179 OTO - NOTNLM OT - ADCS-ADL OT - Alzheimer's disease OT - MMSE OT - OVERTURE clinical trial OT - brain atrophy OT - evoked gamma oscillation COIS- MH, AB, EH, MS, AK, CS, VF, KK, BV, ZM, JM, and RK are employees and own stock options in Cognito Therapeutics, Inc. MH, CS, KK, BV, RK, JM, and ZM have patent applications assigned to Cognito Therapeutics, Inc. JN-J and SH are employees of Pentara who are contracted by Cognito Therapeutics for their service. EDAT- 2024/03/22 06:45 MHDA- 2024/03/22 06:46 PMCR- 2024/03/06 CRDT- 2024/03/22 03:54 PHST- 2023/11/23 00:00 [received] PHST- 2024/02/05 00:00 [accepted] PHST- 2024/03/22 06:46 [medline] PHST- 2024/03/22 06:45 [pubmed] PHST- 2024/03/22 03:54 [entrez] PHST- 2024/03/06 00:00 [pmc-release] AID - 10.3389/fneur.2024.1343588 [doi] PST - epublish SO - Front Neurol. 2024 Mar 6;15:1343588. doi: 10.3389/fneur.2024.1343588. eCollection 2024.