2024
Validating new symptom emergence as a patient-centric outcome measure for PD clinical trials
Zou H, Stebbins G, Simuni T, Luo S, Cedarbaum J. Validating new symptom emergence as a patient-centric outcome measure for PD clinical trials. Parkinsonism & Related Disorders 2024, 128: 107118. PMID: 39353265, DOI: 10.1016/j.parkreldis.2024.107118.Peer-Reviewed Original ResearchPD clinical trialsClinical trialsEmergent symptomsPhase 3 clinical trialsPhase 3 studySlowing of disease progressionOutcome measuresParkinson's diseaseDe novo Parkinson's diseaseMDS-UPDRSItem-level dataFrequency of ESSymptomatic medicationsFrequent administrationMonths of observationEfficacy assessmentDisease progressionSymptom emergenceRating ScaleItem responsesIb and IIUrate elevationTrialsThe ALSFRS-R Summit: a global call to action on the use of the ALSFRS-R in ALS clinical trials
Genge A, Cedarbaum J, Shefner J, Chio A, Al-Chalabi A, Van Damme P, McDermott C, Glass J, Berry J, van Eijk R, Fournier C, Grosskreutz J, Andrews J, Bertone V, Bunte T, Couillard M, Cummings C, Kittle G, Polzer J, Salmon K, Straub C, van den Berg L. The ALSFRS-R Summit: a global call to action on the use of the ALSFRS-R in ALS clinical trials. Amyotrophic Lateral Sclerosis And Frontotemporal Degeneration 2024, 25: 382-387. PMID: 38396337, DOI: 10.1080/21678421.2024.2320880.Peer-Reviewed Original ResearchAmyotrophic Lateral Sclerosis Functional Rating ScaleALSFRS-RClinical trialsStatistical analysis planMonitor functional changesRating ScaleOutcome measuresFunctional Rating ScalePrimary outcome measureClinical trial designALS clinical trialsFunctional changesTrial designTrialsClinical trialistsScaleALS trials
2021
Evaluating dopamine transporter imaging as an enrichment biomarker in a phase 2 Parkinson’s disease trial
Hutchison R, Evans K, Fox T, Yang M, Barakos J, Bedell B, Cedarbaum J, Brys M, Siderowf A, Lang A. Evaluating dopamine transporter imaging as an enrichment biomarker in a phase 2 Parkinson’s disease trial. BMC Neurology 2021, 21: 459. PMID: 34814867, PMCID: PMC8609885, DOI: 10.1186/s12883-021-02470-8.Peer-Reviewed Original ResearchConceptsDAT-SPECTParkinson's diseaseClinical trialsDisease trialsPhase 2 trialDopaminergic nerve terminalsEarly Parkinson's diseaseDisease-modifying therapiesIdiopathic Parkinson's diseaseMulticenter clinical trialParkinson's disease trialStudy design aspectsSingle photon emissionStages of progressionDegenerative parkinsonismEnrichment biomarkerResultsIn totalClinical assessmentNerve terminalsBlinded neuroradiologistsClinical diagnosisDopamine transporterMonoclonal antibodiesCentral laboratoryTrials
2020
Baseline Characteristics of Participants of the SPARK Trial, a Phase 2 Study of the anti-alpha-synuclein antibody Cinpanemab (BIIB054) in Parkinson’s Disease (1579)
Fox T, Siderowf A, Fernandez H, Tanner C, Postuma R, Simon D, Byrne M, Lang A, Brooks D, Rascol O, Tolosa E, Poewe W, Stocchi F, Mollenhauer B, Giladi N, Hirschhorn B, Cedarbaum J, Nomikos G, Fanning L, Yang M, Xiao J, Brys M. Baseline Characteristics of Participants of the SPARK Trial, a Phase 2 Study of the anti-alpha-synuclein antibody Cinpanemab (BIIB054) in Parkinson’s Disease (1579). Neurology 2020, 94 DOI: 10.1212/wnl.94.15_supplement.1579.Peer-Reviewed Original Research
2019
The Qualification of an Enrichment Biomarker for Clinical Trials Targeting Early Stages of Parkinson’s Disease
Stephenson D, Hill D, Cedarbaum JM, Tome M, Vamvakas S, Romero K, Conrado DJ, Dexter DT, Seibyl J, Jennings D, Nicholas T, Matthews D, Xie Z, Imam S, Maguire P, Russell D, Gordon MF, Stebbins GT, Somer E, Gallagher J, Roach A, Basseches P, Grosset D, Marek K, Consortium O. The Qualification of an Enrichment Biomarker for Clinical Trials Targeting Early Stages of Parkinson’s Disease. Journal Of Parkinson's Disease 2019, 9: 825-825. PMID: 31524182, PMCID: PMC6878913, DOI: 10.3233/jpd-199003.Peer-Reviewed Original ResearchMolecular Neuroimaging of the Dopamine Transporter as a Patient Enrichment Biomarker for Clinical Trials for Early Parkinson's Disease
Romero K, Conrado D, Burton J, Nicholas T, Sinha V, Macha S, Ahamadi M, Cedarbaum J, Seibyl J, Marek K, Basseches P, Hill D, Somer E, Gallagher J, Dexter DT, Roach A, Stephenson D, Consortium F, Initiative T. Molecular Neuroimaging of the Dopamine Transporter as a Patient Enrichment Biomarker for Clinical Trials for Early Parkinson's Disease. Clinical And Translational Science 2019, 12: 240-246. PMID: 30706986, PMCID: PMC6510371, DOI: 10.1111/cts.12619.Peer-Reviewed Original ResearchConceptsClinical trialsImaging biomarkersDopamine transporterEuropean Medicines Agency's CommitteeParkinson's disease clinical trialsEarly Parkinson's diseaseCritical Path InstitutePatient selectionEnrichment biomarkerParkinson's diseaseMolecular neuroimagingPharmaceutical partnersDiseaseBiomarkersTrialsQualification opinionHuman useInternational ConsortiumTransportersMedical productsNeuroimaging
2018
Targeted Therapies for Parkinson's Disease: From Genetics to the Clinic
Sardi SP, Cedarbaum JM, Brundin P. Targeted Therapies for Parkinson's Disease: From Genetics to the Clinic. Movement Disorders 2018, 33: 684-696. PMID: 29704272, PMCID: PMC6282975, DOI: 10.1002/mds.27414.Peer-Reviewed Original ResearchConceptsParkinson's diseaseGreat unmet medical needDisease-modifying treatmentsNew therapeutic approachesUnmet medical needClinical stageClinical trialsRelentless progressionTherapeutic approachesPotential therapyClinical developmentTherapeutic paradigmMedical needDiseaseGenetic variantsPD geneticsNew arsenalTreatmentGenetic discoveriesKey outstanding questionsTherapySymptomsPathologyProgressionTrials
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
2006
Dynamic and Quantitative Analysis of Choroidal Neovascularization by Fluorescein Angiography
Shah SM, Tatlipinar S, Quinlan E, Sung JU, Tabandeh H, Nguyen QD, Fahmy AS, Zimmer-Galler I, Symons RC, Cedarbaum JM, Campochiaro PA. Dynamic and Quantitative Analysis of Choroidal Neovascularization by Fluorescein Angiography. Investigative Ophthalmology & Visual Science 2006, 47: 5460-5468. PMID: 17122137, DOI: 10.1167/iovs.06-0012.Peer-Reviewed Original ResearchConceptsFluorescein angiographyFluorescein angiogramsClinical trialsVEGF TrapVascular endothelial growth factor trapPlacebo-treated patientsPhotodynamic therapyChoroidal neovascularization lesion sizeAreas of hyperfluorescenceMacular volumeChoroidal neovascularizationRetrospective gradingOutcome measuresGroup 2Group 1Masked observersPatientsFluorescence areaLesion sizeAngiogramsClinical settingDye injectionInitial assessmentAUCTrials
2001
Disease status and use of ventilatory support by ALS patients
Cedarbaum J, Stambler N. Disease status and use of ventilatory support by ALS patients. Amyotrophic Lateral Sclerosis And Frontotemporal Degeneration 2001, 2: 19-22. PMID: 11465928, DOI: 10.1080/146608201300079373.Peer-Reviewed Original ResearchConceptsMechanical ventilationPlacebo patientsUse of MVRespiratory adverse eventsUse of BiPAPHealth resource utilizationPhase III trialsBiPAP useR-metHuBDNFProspective databaseSymptom durationVentilatory supportAdverse eventsIII trialsALS patientsMean baselinePrescribing practicesVital capacityBehavior of physiciansBiPAPALSFRS scorePatientsMortality rateDisease statusTrials
1997
Performance of the Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS) in multicenter clinical trials
Cedarbaum J, Stambler N. Performance of the Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS) in multicenter clinical trials. Journal Of The Neurological Sciences 1997, 152: s1-s9. PMID: 9419047, DOI: 10.1016/s0022-510x(97)00237-2.Peer-Reviewed Original ResearchConceptsAmyotrophic Lateral Sclerosis Functional Rating ScaleFunctional Rating ScaleMulticenter clinical trialFunctional statusRating ScaleClinical trialsPatients' functional statusClinical Global ImpressionMuscle strength testingArea of feedingPlacebo patientsTherapeutic trialsTest-retest reliabilityGlobal ImpressionPatient levelTreatment studiesChange ScaleTrialsPatientsMaximum scoreIndependent assessmentStrength testingAmbulation
1988
Clinical significance of the relationship between O-methyldopa levels and levodopa intake.
Cedarbaum J, Kutt H, McDowell F. Clinical significance of the relationship between O-methyldopa levels and levodopa intake. Neurology 1988, 38: 533-6. PMID: 3352906, DOI: 10.1212/wnl.38.4.533.Peer-Reviewed Original ResearchConceptsDaily intakeRecent clinical trialsMean daily intakeTotal daily intakeLevodopa intakeStandard SinemetClinical responseLevodopa preparationsBrain uptakeClinical trialsPlasma concentrationsClinical significanceBlood samplingLevodopaTherapeutic efficacyMethyldopa levelsControlled-release formulationPatientsIntakeTime curveAUCSinemetLevelsTrials
1987
Controlled-release levodopa/carbidopa. I. Sinemet CR3 treatment of response fluctuations in Parkinson's disease.
Cedarbaum J, Breck L, Kutt H, McDowell F. Controlled-release levodopa/carbidopa. I. Sinemet CR3 treatment of response fluctuations in Parkinson's disease. Neurology 1987, 37: 233-41. PMID: 3808304, DOI: 10.1212/wnl.37.2.233.Peer-Reviewed Original ResearchConceptsPlasma levodopa levelsLevodopa levelsResponse fluctuationsParkinson's diseaseControlled-release carbidopa/levodopaCarbidopa/levodopaOpen-label trialBioavailability of levodopaStandard SinemetDisability scoresLevodopa preparationsInterdose intervalDaily dosesParkinson's patientsControlled-release formulationClinical performanceDiseaseLevodopaDay consistencyOverall benefitSinemetPatientsDosesTrialsWeeks