title: Double-blind placebo-controlled study of velnacrine in Alzheimer's disease.
abstract: The present study assessed the safety and efficacy of the cholinesterase inhibitor, velnacrine, for treating the cognitive symptoms of Alzheimer's disease. Patients (N = 236) meeting NINCDS-ADRDA criteria for Alzheimer's disease entered a double-blind, placebo-controlled dose-ranging protocol (30, 75, 150, 225 mg/day each for one week) to identify velnacrine responders (> or = four point improvement on the cognitive subscale of the Alzheimer's Disease Assessment Scale [ADAScog]). After a two week drug washout, velnacrine responders were randomly assigned to their best velnacrine dose or placebo in a six week dose-replication protocol employing the ADAScog and the Clinical Global Improvement scale as primary outcome measures. During dose-replication, intent-to-treat analysis revealed that velnacrine patients scored significantly better than placebo patients on the ADAScog after two (p < 0.004), four (p < 0.025) and six (p < 0.001) weeks of treatment. No significant treatment effect on Clinical Global Improvement scores was observed. The primary adverse event was an asymptomatic elevation of liver transaminases found among 28% of the 236 treated patients. Cholinergic side effects including diarrhea (14%), nausea (11%) and vomiting (5%) were observed and 8% of patients experienced skin rash. The present study identified a subgroup of Alzheimer's patients who demonstrated a significant, but modest, improvement during velnacrine treatment on structured cognitive testing.
authors.affiliation: Alzheimer's Research Center, Department of Psychiatry, University of Cincinnati College of Medicine, OH 45267-0559, USA.
authors.forename: F P
authors.initials: FP
authors.lastname: Zemlan
authors.forename: M
authors.initials: M
authors.lastname: Keys
authors.forename: R W
authors.initials: RW
authors.lastname: Richter
authors.forename: R L
authors.initials: RL
authors.lastname: Strub
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000188:drug therapy*; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010919:Placebos; D013619:Tacrine / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D002800:Cholinesterase Inhibitors; D010919:Placebos; D013619:Tacrine; C056424:velnacrine