biostudies-literatureBerry JDNCATS NIH HHSNINDS NIH HHSe61177https://www.ebi.ac.uk/biostudies/studies/S-EPMC3629222biostudies-literatureUnknown8(4)<h4>Objectives</h4>Ceftriaxone increases expression of the astrocytic glutamate transporter, EAAT2, which might protect from glutamate-mediated excitotoxicity. A trial using a novel three stage nonstop design, incorporating Phases I-III, tested ceftriaxone in ALS. Stage 1 determined the cerebrospinal fluid pharmacokinetics of ceftriaxone in subjects with ALS. Stage 2 evaluated safety and tolerability for 20-weeks. Analysis of the pharmacokinetics, tolerability, and safety was used to determine the ceftriaxone dosage for Stage 3 efficacy testing.<h4>Methods</h4>In Stage 1, 66 subjects at ten clinical sites were enrolled and randomized equally into three study groups receiving intravenous placebo, ceftriaxone 2 grams daily or ceftriaxone 4 grams daily divided BID. Participants provided serumPloS oneDesign and initial results of a multi-phase randomized trial of ceftriaxone in amyotrophic lateral sclerosis.PMC3629222U01 NS049640-05U01 NS049640R01 NS049640UL1 TR000448Caress JBSimpson EKeroack MConwit RRezania KRosenfeld JVriesendorp FBerry JDKatz JPascuzzi RRothstein JDGreenblatt DJPestronk AGlass JDavid WSCudkowicz MEShefner JMSchoenfeld DKrivickas LFelsenstein DNortheast ALS ConsortiumfalseDesign and initial results of a multi-phase randomized trial of ceftriaxone in amyotrophic lateral sclerosis.<h4>Objectives</h4>Ceftriaxone increases expression of the astrocytic glutamate transporter, EAAT2, which might protect from glutamate-mediated excitotoxicity. A trial using a novel three stage nonstop design, incorporating Phases I-III, tested ceftriaxone in ALS. Stage 1 determined the cerebrospinal fluid pharmacokinetics of ceftriaxone in subjects with ALS. Stage 2 evaluated safety and tolerability for 20-weeks. Analysis of the pharmacokinetics, tolerability, and safety was used to determine the ceftriaxone dosage for Stage 3 efficacy testing.<h4>Methods</h4>In Stage 1, 66 subjects at ten clinical sites were enrolled and randomized equally into three study groups receiving intravenous placebo, ceftriaxone 2 grams daily or ceftriaxone 4 grams daily divided BID. Participants provided serum2013-01-01T00:00:00Z20132026-05-02T08:17:15.922Z2019-03-26T23:14:10ZS-EPMC36292222361380610.1371/journal.pone.0061177