Research
Neuropsychobiology. 1997;36(2):73-82.
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, Frankfurt/Main, Germany.
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.
Publication Types: Clinical Trial, Multicenter Study, Randomized Controlled Trial
PMID: 9267856 [PubMed - indexed for MEDLINE]
Mov Disord. 1996 Sep;11(5):549-54.
A controlled trial of idebenone in Huntington's disease.
Ranen NG, Peyser CE, Coyle JT, Bylsma FW, Sherr M, Day L, Folstein MF, Brandt J, Ross CA, Folstein SE.
Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
One hundred patients with clinically diagnosed Huntington's disease (HD) were randomized to either idebenone, an antioxidant and enhancer of oxidative metabolism, or placebo, in a 1-year, double-blind, parallel-group study aimed at slowing the rate of progression of the disease. Ninety-one patients completed the study. There were no significant differences between groups on the primary outcome measures of the Huntington's Disease Activities of Daily Living Scale (ADL-an index of functional status) and the Quantified Neurologic Examination (QNE). Sample size calculations based on progression of the ADL and QNE in this study group revealed that a larger study group is necessary to detect any differences less than an almost complete halting of the disease. This argues for multicenter efforts for future therapeutic trials in HD.
Publication Types: Clinical Trial, Randomized Controlled Trial,
PMID: 8866496 [PubMed - indexed for MEDLINE]
Neurology. 1996 Aug;47(2):583-5.
Idebenone improves cerebral mitochondrial oxidative metabolism in a patient with MELAS.
Ikejiri Y, Mori E, Ishii K, Nishimoto K, Yasuda M, Sasaki M.
Division of Clinical Neurosciences, Hyogo Institute for Aging Brain and Cognitive Disorders, Himeji, Japan.
We report a 36-year-old man with MELAS in whom a 5-month course of high-dose oral idebenone, a derivative
of coenzyme Q10, increased markedly cerebral metabolic ratio of oxygen and oxygen extraction fraction without increased cerebral blood flow with PET. The results indicate that idebenone improves mitochondrial oxidative metabolism in the brain and suggest a therapeutic potential of idebenone for MELAS.
Publication Types: Case Reports
PMID: 8757046 [PubMed - indexed for MEDLINE]
