2022
Trial of Cinpanemab in Early Parkinson’s Disease
Lang A, Siderowf A, Macklin E, Poewe W, Brooks D, Fernandez H, Rascol O, Giladi N, Stocchi F, Tanner C, Postuma R, Simon D, Tolosa E, Mollenhauer B, Cedarbaum J, Fraser K, Xiao J, Evans K, Graham D, Sapir I, Inra J, Hutchison R, Yang M, Fox T, Budd Haeberlein S, Dam T. Trial of Cinpanemab in Early Parkinson’s Disease. New England Journal Of Medicine 2022, 387: 408-420. PMID: 35921450, DOI: 10.1056/nejmoa2203395.Peer-Reviewed Original ResearchConceptsEarly Parkinson's diseasePrimary end pointSecondary end pointsWeek 52Parkinson's diseaseEnd pointControl groupUnified Parkinson's Disease Rating Scale (UPDRS) total scoreDisease pathogenesisHuman-derived monoclonal antibodiesΑ-synucleinCommon adverse eventsPhase 2 trialDisease-modifying treatmentsMDS-UPDRS scoresLack of efficacyDAT SPECT imagingAdjusted mean differenceMovement Disorder SocietyParkinson's disease pathogenesisScale total scoreAdverse eventsIntravenous infusionDAT-SPECTDisease progression
2012
Safety, tolerability and pharmacodynamics of a skeletal muscle activator in amyotrophic lateral sclerosis
Shefner J, Cedarbaum JM, Cudkowicz ME, Maragakis N, Lee J, Jones D, Watson ML, Mahoney K, Chen M, Saikali K, Mao J, Russell AJ, Hansen RL, Malik F, Wolff AA, Team F. Safety, tolerability and pharmacodynamics of a skeletal muscle activator in amyotrophic lateral sclerosis. Amyotrophic Lateral Sclerosis And Frontotemporal Degeneration 2012, 13: 430-438. PMID: 22591195, DOI: 10.3109/17482968.2012.684214.Peer-Reviewed Original ResearchConceptsAmyotrophic lateral sclerosisSingle dosesGlobal ImpressionLateral sclerosisFast skeletal muscle troponin activatorFrequent adverse eventsDose-related fashionLimb muscle strengthMaximum voluntary ventilationDose-dependent benefitMeasures of enduranceAdverse eventsPulmonary functionVoluntary ventilationGeneral fatigueTroponin activatorMuscle strengthPharmacodynamic markersHandgrip endurancePatientsRandom orderMaximal strengthDosesTolerabilityFurther studies
2011
A phase 2 randomized trial of ELND005, scyllo-inositol, in mild to moderate Alzheimer disease
Salloway S, Sperling R, Keren R, Porsteinsson AP, van Dyck CH, Tariot PN, Gilman S, Arnold D, Abushakra S, Hernandez C, Crans G, Liang E, Quinn G, Bairu M, Pastrak A, Cedarbaum JM. A phase 2 randomized trial of ELND005, scyllo-inositol, in mild to moderate Alzheimer disease. Neurology 2011, 77: 1253-1262. PMID: 21917766, PMCID: PMC3179648, DOI: 10.1212/wnl.0b013e3182309fa5.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, OralAgedAged, 80 and overAlzheimer DiseaseAmyloid beta-PeptidesApolipoprotein E4Dose-Response Relationship, DrugDouble-Blind MethodFemaleFollow-Up StudiesHumansInositolMagnetic Resonance ImagingMaleMental Status ScheduleMiddle AgedPeptide FragmentsPlatelet Aggregation InhibitorsTime FactorsTreatment OutcomeConceptsNeuropsychological test batteryAlzheimer's diseaseDose-ranging phase 2 studyAlzheimer's Disease Cooperative Study-ActivitiesClass II trialsClinical efficacy outcomesCSF biomarker resultsScyllo-inositol concentrationsPhase 2 studyPrimary efficacy analysisHigh-dose groupDaily Living ScaleBrain ventricular volumeCoprimary endpointsEarly discontinuationEfficacy outcomesII trialADCS-ADLDose groupEfficacy analysisAcceptable safetyAβx-42Living ScaleOptimal doseTreatment groupsSuitability of the Clinical Dementia Rating‐Sum of Boxes as a single primary endpoint for Alzheimer's disease trials
Coley N, Andrieu S, Jaros M, Weiner M, Cedarbaum J, Vellas B. Suitability of the Clinical Dementia Rating‐Sum of Boxes as a single primary endpoint for Alzheimer's disease trials. Alzheimer's & Dementia 2011, 7: 602-610.e2. PMID: 21745761, DOI: 10.1016/j.jalz.2011.01.005.Peer-Reviewed Original ResearchConceptsClinical Dementia Rating SumCo-primary endpointsPrimary endpointSingle primary endpointCDR-SBInternal responsivenessFunctional impairmentADAS-CogDisease trialsExternal responsivenessAlzheimer's diseaseAlzheimer's Disease Assessment Scale-cognitive subscaleFloor/ceiling effectsCDR-SB changeDisease-modifying trialsModerate AD patientsDaily Living ScaleAlzheimer's disease trialsConvergent validityInternal consistencyAD trialsDisease stageAD patientsInstrumental activitiesMean change
2010
Seeing with new eyes: Finding a path to early intervention trials in Alzheimer's disease
Cedarbaum JM, Crans G, Grundman M. Seeing with new eyes: Finding a path to early intervention trials in Alzheimer's disease. The Journal Of Nutrition Health & Aging 2010, 14: 306-309. PMID: 20306002, DOI: 10.1007/s12603-010-0069-y.Peer-Reviewed Original ResearchConceptsMild cognitive impairmentAlzheimer's diseaseOutcome measuresClinical Dementia Rating SumClinical staging algorithmsPrimary outcome measureAD clinical trialsEarly intervention trialsComprehensive outcome measuresIdentification of MCIClinical courseIntervention trialsAD patientsClinical trialsDementia pathologyClinical characterizationCognitive impairmentEarly identificationDegenerative disordersNormal cognitionStaging algorithmDiseaseBiomarker informationBiomarker dataTrials
2009
A Phase I Study of Intravitreal Vascular Endothelial Growth Factor Trap-Eye in Patients with Neovascular Age-Related Macular Degeneration
Nguyen QD, Shah SM, Browning DJ, Hudson H, Sonkin P, Hariprasad SM, Kaiser P, Slakter JS, Haller J, V. D, Mieler WF, Chu K, Yang K, Ingerman A, Vitti RL, Berliner AJ, Cedarbaum JM, Campochiaro PA. A Phase I Study of Intravitreal Vascular Endothelial Growth Factor Trap-Eye in Patients with Neovascular Age-Related Macular Degeneration. Ophthalmology 2009, 116: 2141-2148.e1. PMID: 19700196, DOI: 10.1016/j.ophtha.2009.04.030.Peer-Reviewed Original ResearchMeSH KeywordsAgedAged, 80 and overChoroidal NeovascularizationFemaleFluorescein AngiographyFollow-Up StudiesHumansInjectionsMacular DegenerationMaleMaximum Tolerated DoseReceptors, Vascular Endothelial Growth FactorRecombinant Fusion ProteinsTomography, Optical CoherenceTreatment OutcomeVisual AcuityVitreous BodyConceptsVEGF Trap-EyeAge-related macular degenerationVascular endothelial growth factor (VEGF) Trap-EyeNeovascular age-related macular degenerationNeovascular AMDChoroidal neovascularizationOptical coherence tomographyFoveal thicknessIntravitreal injectionVisual acuityMacular degenerationMean increaseArea of CNVExcess foveal thicknessSingle intraocular injectionPrimary end pointSerious adverse eventsPhase III trialsHigh-dose groupInterventional clinical trialsActive choroidal neovascularizationNumber of patientsHuman immunoglobulin G (IgG) FcVEGF receptor 1VEGF family members
2005
NT-3 promotes nerve regeneration and sensory improvement in CMT1A mouse models and in patients
Sahenk Z, Nagaraja HN, McCracken BS, King WM, Freimer ML, Cedarbaum JM, Mendell JR. NT-3 promotes nerve regeneration and sensory improvement in CMT1A mouse models and in patients. Neurology 2005, 65: 681-689. PMID: 16157899, DOI: 10.1212/01.wnl.0000171978.70849.c5.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAnimalsCharcot-Marie-Tooth DiseaseDisease Models, AnimalDouble-Blind MethodFemaleHumansMaleMiceMice, Neurologic MutantsMice, NudeMice, TransgenicMiddle AgedMyelin ProteinsNerve RegenerationNeurotrophin 3Pilot ProjectsRecovery of FunctionSciatic NeuropathySural NerveTransplantation, HeterologousTreatment OutcomeConceptsNeuropathy Impairment ScoreNT-3 groupNT-3 treatmentNeurotrophin-3Placebo groupAnimal modelsNerve regenerationNude mice axonsQuantitative muscle testingSural nerve biopsyPrimary outcome measurePeripheral myelin proteinPilot clinical studyTooth type 1ANerve biopsyMuscle testingAxonal regenerationClinical studiesImpairment scoresOutcome measuresPreclinical studiesMouse modelEndpoint measuresElectrophysiologic measurementsNude mice
2003
Neurotrophin-3 Improves Functional Constipation
Parkman HP, Rao SS, Reynolds JC, Schiller LR, Wald A, Miner PB, Lembo AJ, Gordon JM, Drossman DA, Waltzman L, Stambler N, Cedarbaum JM. Neurotrophin-3 Improves Functional Constipation. The American Journal Of Gastroenterology 2003, 98: ajg2003312. PMID: 12818279, DOI: 10.1111/j.1572-0241.2003.t01-1-07477.x.Peer-Reviewed Original ResearchConceptsComplete bowel movementsNeurotrophin-3Bowel movementsColon transitFunctional constipationChronic constipationStool frequencyPlacebo-controlled phase II studyTransient injection site reactionsConstipation-related symptomsFrequent adverse eventsPhase II studyThird of patientsInjection site reactionsEnd of treatmentDose-related effectsConstipated subjectsBowel functionPrimary endpointAdverse eventsII studyImproved symptomsWeekly dosingNeurotrophic factorConstipation