2024
Post hoc analysis of ADAMANT, a phase 2 clinical trial of active tau immunotherapy with AADvac1 in patients with Alzheimer’s disease, positive for plasma p-tau217
Kovacech B, Cullen N, Novak P, Hanes J, Kontsekova E, Katina S, Parrak V, Fresser M, Vanbrabant J, Feldman H, Winblad B, Stoops E, Vanmechelen E, Zilka N. Post hoc analysis of ADAMANT, a phase 2 clinical trial of active tau immunotherapy with AADvac1 in patients with Alzheimer’s disease, positive for plasma p-tau217. Alzheimer's Research & Therapy 2024, 16: 254. PMID: 39580468, PMCID: PMC11585249, DOI: 10.1186/s13195-024-01620-7.Peer-Reviewed Original ResearchConceptsClinical Dementia Rating-Sum of BoxesPhase 2 clinical trialGlial fibrillary acidic proteinPost hoc analysisAlzheimer's diseaseAlzheimer's Disease Cooperative Study ActivitiesPlasma p-tau217Clinical Dementia Rating-SumClinical trialsWhole-brain volumeSpread of tau pathologyPlasma biomarkers of neurodegenerationPlasma P-tau217 levelsMicrotubule-binding regionSubgroup of participantsADAMS participantsTau pathologyAD-related neuropathological changesCognitive declineFibrillary acidic proteinActive immunotherapyDouble-blindPlacebo-controlledVolumetric MRITau immunotherapyVaroglutamstat: Inhibiting Glutaminyl Cyclase as a Novel Target of Therapy in Early Alzheimer’s Disease
Feldman H, Messer K, Qiu Y, Sabbagh M, Galasko D, Turner R, Lopez O, Smith A, Durant J, Lupo J, Revta C, Balasubramanian A, Kuehn-Wache K, Wassmann T, Schell-Mader S, Jacobs D, Salmon D, Léger G, DeMarco M, Weber F, Group F. Varoglutamstat: Inhibiting Glutaminyl Cyclase as a Novel Target of Therapy in Early Alzheimer’s Disease. Journal Of Alzheimer's Disease 2024, 101: s79-s93. PMID: 39422941, PMCID: PMC11494639, DOI: 10.3233/jad-231126.Peer-Reviewed Original ResearchConceptsGlutaminyl cyclasePost-translationallyAlzheimer's diseasePhase 2bEarly phase clinical trialsAmyloid-bCytokine monocyte chemoattractant protein-1Monocyte chemoattractant protein-1Highest tolerated doseLonger-term safetyPhase clinical trialsWeeks of treatmentFirst-in-classTarget of therapyUnique dual mechanismChemoattractant protein-1Interim futility analysisClinical efficacyDisease cascadeProtein 1Electroencephalogram changesOptimal doseClinical trialsAnalysis of cognitive functionHigh dosesA multicenter, randomized, double-blind, placebo-controlled ascending dose study to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamic (PD) effects of Posiphen in subjects with early Alzheimer’s Disease
Galasko D, Farlow M, Lucey B, Honig L, Elbert D, Bateman R, Momper J, Thomas R, Rissman R, Pa J, Aslanyan V, Balasubramanian A, West T, Maccecchini M, Feldman H. A multicenter, randomized, double-blind, placebo-controlled ascending dose study to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamic (PD) effects of Posiphen in subjects with early Alzheimer’s Disease. Alzheimer's Research & Therapy 2024, 16: 151. PMID: 38970127, PMCID: PMC11225352, DOI: 10.1186/s13195-024-01490-z.Peer-Reviewed Original ResearchConceptsOrally administered small moleculeFractional synthesis rateAscending dose studyDose-dependent loweringIRB-approved protocolEarly ADMini-Mental State ExamDose-dependent effectAlzheimer's diseaseBlood patchDouble-blindWell-toleratedCatheter placementPreclinical modelsLumbar punctureDose studyIntravenous infusionMild cognitive impairmentEvaluate safetyPlacebo participantsCognitive measuresStable isotope labeling kineticsActive drugClinical trialsADAS-Cog12Asian Cohort for Alzheimer Disease (ACAD) Pilot Study
Peavy G, Võ N, Revta C, Lu A, Lupo J, Nam P, Nguyễn K, Wang L, Feldman H. Asian Cohort for Alzheimer Disease (ACAD) Pilot Study. Alzheimer Disease & Associated Disorders 2024, 38: 277-284. PMID: 39177172, PMCID: PMC11340683, DOI: 10.1097/wad.0000000000000631.Peer-Reviewed Original ResearchConceptsSubjective cognitive complaintsOlder Vietnamese AmericansVascular risk factorsMild cognitive impairmentVietnamese AmericansRisk factorsMeasuring subjective cognitive complaintsPilot studyCommunity advisory boardNongenetic risk factorsCommunity-based researchAD risk factorsAlzheimer's diseaseDepressive symptomsConsensus teamCognitive complaintsBilingual/bicultural staffAD riskAssessment toolAdvisory boardVietnamese communityExploratory analysisCognitive difficultiesCognitive impairmentParticipantsProtocol for a seamless phase 2A-phase 2B randomized double-blind placebo-controlled trial to evaluate the safety and efficacy of benfotiamine in patients with early Alzheimer’s disease (BenfoTeam)
Feldman H, Luchsinger J, Léger G, Taylor C, Jacobs D, Salmon D, Edland S, Messer K, Revta C, Flowers S, Jones K, Koulman A, Yarasheski K, Verghese P, Venkatesh V, Zetterberg H, Durant J, Lupo J, Gibson G, Group F. Protocol for a seamless phase 2A-phase 2B randomized double-blind placebo-controlled trial to evaluate the safety and efficacy of benfotiamine in patients with early Alzheimer’s disease (BenfoTeam). PLOS ONE 2024, 19: e0302998. PMID: 38809849, PMCID: PMC11135745, DOI: 10.1371/journal.pone.0302998.Peer-Reviewed Original ResearchConceptsPhase 2bPhase 2aRandomized double-blind placebo-controlled trialDouble-blind placebo-controlled trialCo-primary efficacy endpointsTolerability eventsBest-tolerated dosePlacebo-controlled trialWell-tolerated dosesAlzheimer's diseaseLonger-term safetyEfficacy of drug deliveryWeeks of treatmentTargeted therapeutic approachesErythrocyte transketolase activityGroups of participantsDouble-blindPlacebo armEfficacy endpointSecondary endpointsOral treatmentPharmacokinetic measurementsClinical trialsTherapeutic approachesBlood markers
2023
Efficacy assessment of an active tau immunotherapy in Alzheimer’s disease patients with amyloid and tau pathology: a post hoc analysis of the “ADAMANT” randomised, placebo-controlled, double-blind, multi-centre, phase 2 clinical trial
Cullen N, Novak P, Tosun D, Kovacech B, Hanes J, Kontsekova E, Fresser M, Ropele S, Feldman H, Schmidt R, Winblad B, Zilka N. Efficacy assessment of an active tau immunotherapy in Alzheimer’s disease patients with amyloid and tau pathology: a post hoc analysis of the “ADAMANT” randomised, placebo-controlled, double-blind, multi-centre, phase 2 clinical trial. EBioMedicine 2023, 99: 104923. PMID: 38101301, PMCID: PMC10733085, DOI: 10.1016/j.ebiom.2023.104923.Peer-Reviewed Original ResearchConceptsTau pathologyPathological tau proteinsAlzheimer's diseaseDouble-blindPlacebo-controlledCDR-SBTau immunotherapyTau proteinPhase 2 clinical trialAnti-tauPost hoc subgroup analysisAD-related declineDisease patientsSlowing of declineAlzheimer's disease patientsAntibody-dependent mannerAADvac1Post hoc analysisActive immunotherapyTauFull analysisParallel-groupSubgroup analysisBaseline MRIEfficacy assessment
2012
Predicting missing biomarker data in a longitudinal study of Alzheimer disease
Lo R, Jagust W, Aisen P, Jack C, Toga A, Beckett L, Gamst A, Soares H, C. Green R, Montine T, Thomas R, Donohue M, Walter S, Dale A, Bernstein M, Felmlee J, Fox N, Thompson P, Schuff N, Alexander G, DeCarli C, Bandy D, Chen K, Morris J, Lee V, Korecka M, Crawford K, Neu S, Harvey D, Kornak J, Saykin A, Foroud T, Potkin S, Shen L, Buckholtz N, Kaye J, Dolen S, Quinn J, Schneider L, Pawluczyk S, Spann B, Brewer J, Vanderswag H, Heidebrink J, Lord J, Petersen R, Johnson K, Doody R, Villanueva-Meyer J, Chowdhury M, Stern Y, Honig L, Bell K, Morris J, Mintun M, Schneider S, Marson D, Griffith R, Clark D, Grossman H, Tang C, Marzloff G, Toledo-Morrell L, Shah R, Duara R, Varon D, Roberts P, Albert M, Pedroso J, Toroney J, Rusinek H, de Leon M, De Santi S, Doraiswamy P, Petrella J, Aiello M, Clark C, Pham C, Nunez J, Smith C, Given C, Hardy P, Lopez O, Oakley M, Simpson D, Ismail M, Brand C, Richard J, Mulnard R, Thai G, Mc-Adams-Ortiz C, Diaz-Arrastia R, Martin-Cook K, DeVous M, Levey A, Lah J, Cellar J, Burns J, Anderson H, Laubinger M, Bartzokis G, Silverman D, Lu P, Graff-Radford MBBCH N, Parfitt F, Johnson H, Farlow M, Herring S, Hake A, van Dyck C, MacAvoy M, Benincasa A, Chertkow H, Bergman H, Hosein C, Black S, Graham S, Caldwell C, Hsiung G, Feldman H, Assaly M, Kertesz A, Rogers J, Trost D, Bernick C, Munic D, Wu C, Johnson N, Mesulam M, Sadowsky C, Martinez W, Villena T, Turner S, Johnson K, Behan K, Sperling R, Rentz D, Johnson K, Rosen A, Tinklenberg J, Ashford W, Sabbagh M, Connor D, Jacobson S, Killiany R, Norbash A, Nair A, Obisesan T, Jayam-Trouth A, Wang P, Lerner A, Hudson L, Ogrocki P, DeCarli C, Fletcher E, Carmichael O, Kittur S, Mirje S, Borrie M, Lee T, Bartha D, Johnson S, Asthana S, Carlsson C, Potkin S, Preda A, Nguyen D, Tariot P, Fleisher A, Reeder S, Bates V, Capote H, Rainka M, Hendin B, Scharre D, Kataki M, Zimmerman E, Celmins D, Brown A, Gandy S, Marenberg M, Rovner B, Pearlson G, Anderson K, Saykin A, Santulli R, Englert J, Williamson J, Sink K, Watkins F, Ott B, Wu C, Cohen R, Salloway S, Malloy P, Correia S, Rosen H, Miller B, Mintzer J. Predicting missing biomarker data in a longitudinal study of Alzheimer disease. Neurology 2012, 78: 1376-1382. PMID: 22491869, PMCID: PMC3345787, DOI: 10.1212/wnl.0b013e318253d5b3.Peer-Reviewed Original ResearchAlzheimer DiseaseAmyloid beta-PeptidesBiomarkersCognitive DysfunctionCohort StudiesDementia, VascularFluorodeoxyglucose F18HomocysteineHumansLogistic ModelsLongitudinal StudiesMagnetic Resonance ImagingNeuropsychological TestsPatient DropoutsPeptide FragmentsPositron-Emission TomographyResearch DesignRisk FactorsTau Proteins