A controlled study of 2 doses of idebenone
in the treatment of Alzheimer's disease.
Weyer G, Babej-Dolle RM, Hadler D, Hofmann S, Herrmann WM.
Institute of Psychology,
Johann Wolfgang Goethe University,
Two doses of idebenone were
studied in a prospective, randomized, double-blind, placebo-controlled
multicentre study in patients suffering from dementia of the Alzheimer type
(DAT) of mild to moderate degree. Diagnosis was based on DSM-III-R
(primary degenerative dementia) and NINCDS-ADRDA criteria (probable
Alzheimer's disease). A total of 300 patients were randomized to either
placebo, idebenone 30 mg t.i.d. or 90 mg t.i.d. (n = 100, each) and
treated for 6 months. The primary outcome measure was the total score of the
Alzheimer's Disease Assessment Scale (ADAS-Total) at month 6. Secondary
outcome measures were the ADAS cognitive (ADAS-Cog) and noncognitive scores (ADAS-Noncog),
the clinical global response (CGI-Improvement), the MMSE, the Digit Symbol
Substitution test (DSS) and several scales for the assessment of daily
activities (the self- and observer-rating scales NAA and NAB of the Nuremberg
Age Inventory NAI and Greene's Assessment). Safety parameters were adverse
events, vital signs, ECG and clinical laboratory parameters. Clinical and
psychometric evaluations were performed at baseline, and after 1, 3 and 6
months of treatment. After month 6 idebenone 90 mg t.i.d. showed
statistically significant improvement in the primary efficacy variable ADAS-Total
and in ADAS-Cog. An analysis of therapy responders performed for 3 outcome
measures (CGI-global improvement, ADAS-Cog, ADAS-Noncog), selected to
represent different domains of assessment, revealed significant superiority of
idebenone 90 mg t.i.d. with respect to placebo in each of the 3
variables and in the concordance of responses across the 3 measures.
Exploratory results for a subgroup of patients (ADAS-Total > or = 20)
showed dose-related superiority of idebenone additionally on
ADAS-Noncog and the CGI-Improvement scale. Safety results were inconspicuous
for all assessments. The study results demonstrate the efficacy and safety of idebenone
in the treatment of DAT patients.