Monique C J Koks-Leensen, Anouk Menko, Fieke Raaijmakers, Gerdine A J Fransen-Kuppens, Kirsten E Bevelander
An Accessible Web-based Survey to Monitor the Mental Health of People with Mild Intellectual Disabilities and/or Low Literacy Skills during the COVID-19 Pandemic: Comparative Data Analysis
JMIR public health and surveillance
amyotrophic lateral sclerosis progressive neurodegenerative disorder leading muscle weakness respiratory failure arimoclomol heatshock protein70 hsp70 coinducer neuroprotective animal models amyotrophic lateral sclerosis multiple mechanisms action including clearance protein aggregates pathological hallmark sporadic familial amyotrophic lateral sclerosis aimed evaluate safety efficacy arimoclomol patients amyotrophic lateral sclerosis orarials01 multinational randomised doubleblind placebocontrolled parallelgroup trial done 29 centres 12 countries europe north america patients eligible aged 18 years older met el escorial criteria clinically possible probable probable laboratorysupported definite familial amyotrophic lateral sclerosis als functional rating scalerevised score 35 slow vital capacity 70 value predicted basis participants age height sex patients randomly assigned 21 blocks 6 stratified use stable dose riluzole riluzole use receive oral arimoclomol citrate 1200 mgday 400 mg three times per day placebo randomisation sequence computer generated centrally investigators study personnel study participants masked treatment allocation primary outcome combined assessment function survival cafs rank score 76 weeks treatment primary outcome safety analysed modified intentiontotreat population trial registered clinicaltrialsgov nct03491462 completed july 31 2018 july 17 2019 287 patients screened 245 enrolled trial randomly assigned modified intentiontotreat population comprised 239 patients 160 arimoclomol group 79 placebo group 151 63 male 88 37 female mean age 576 years sd 109 cafs score 76 weeks differ groups mean 051 sd 029 arimoclomol group vs 049 028 placebo group p062 cliffs delta comparing two groups 0039 95 ci 0116 0194 proportions participants died similar treatment groups 29 18 160 patients arimoclomol group 18 23 79 patients placebo group deaths due disease progression common adverse events gastrointestinal adverse events often deemed treatmentrelated arimoclomol group 104 65 placebo group 41 52 often led treatment discontinuation arimoclomol group 26 16 placebo group four 5 arimoclomol improve efficacy outcomes compared placebo although available biomarker data insufficient preclude future strategies target hsp response safety data suggest higher dose arimoclomol would tolerated orphazyme