{"doi":"10.14283/jpad.2024.154","title":"A Pilot Electroencephalography Study of the Effect of CT1812 Treatment on Synaptic Activity in Patients with Mild to Moderate Alzheimer's Disease","abstract":"BACKGROUND: CT1812 is a first-in-class, sigma-2 receptor ligand, that prevents and displaces binding of amyloid beta (Aβ) oligomers. Normalization of quantitative electroencephalography (qEEG) markers suggests that CT1812 protects synapses from Aβ oligomer toxicity. OBJECTIVES: Evaluate CT1812 impact on synaptic function using qEEG measurements. DESIGN: Phase 2, randomized, double-blind, placebo-controlled, 4-week crossover study. SETTING: VU University Medical Center and Brain Research Center Amsterdam, The Netherlands. PARTICIPANTS: Adults with mild or moderate Alzheimer's disease (AD). INTERVENTION: A daily 300 mg dose of CT1812 or placebo for 4 weeks. MEASUREMENTS: A resting-state, eyes closed qEEG assessment occurred on Day 1 and on Day 29 of Treatment Periods 1 and 2, and at follow-up. The primary endpoint was global relative theta power (4-8 Hz), along with secondary EEG measures including global alpha corrected Amplitude Envelope Correlation (AEC-c). Cognitive and functional assessments, fluid biomarkers, and safety and tolerability were assessed. RESULTS: 16 patients were randomized, and 15 completed. A non-significant (p=0.123) but consistent reduction occurred in global relative theta power and in relative theta power in frontal, temporal, parietal, occipital and central (p<0.006) brain regions with CT1812. A nominally significant (p=0.034) improvement was observed in global alpha AEC-c. Adverse events occurred in 11 patients with CT1812 and 6 with placebo - most commonly nausea, diarrhea, and procedural headache. No severe or serious AEs, deaths or discontinuations were reported. CONCLUSION: CT1812 improved established EEG markers of spontaneous brain activity (spectral power, functional connectivity) in patients with mild-to-moderate AD, suggesting improved neuronal/synaptic function within a 4-week timespan.","journal":"The Journal of Prevention of Alzheimer s Disease","year":2024,"id":434266,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":13,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9465,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1240425,"name":"Willem de Haan","orcid":"0000-0002-0527-9667","position":1,"is_corresponding":false},{"id":1240930,"name":"E. Scheijbeler","orcid":null,"position":2,"is_corresponding":false},{"id":1240931,"name":"Madison Hamby","orcid":null,"position":3,"is_corresponding":false},{"id":951082,"name":"Stefania Catalano","orcid":"0000-0002-6352-9628","position":4,"is_corresponding":false},{"id":226631,"name":"Philip Scheltens","orcid":"0000-0002-1046-6408","position":5,"is_corresponding":false},{"id":1046009,"name":"Michael Grundman","orcid":null,"position":6,"is_corresponding":false},{"id":1046010,"name":"Anthony O. Caggiano","orcid":null,"position":7,"is_corresponding":false},{"id":233783,"name":"Everard G.B. Vijverberg","orcid":"0000-0003-3879-884X","position":0,"is_corresponding":true}],"reference_count":46,"raw_metadata":null,"created_at":"2026-07-19T01:59:53.957667Z","pmid":"39559892","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}