Efficacy and Safety of Cilostazol in Mild Cognitive Impairment: A Randomized Clinical Trial.

Autor:	Saito S; Department of Neurology, National Cerebral and Cardiovascular Center, Suita, Japan., Suzuki K; Innovation Center for Translational Research, National Center for Geriatrics and Gerontology, Obu, Japan., Ohtani R; Department of Neurology, National Hospital Organization Kyoto Medical Center, Kyoto, Japan., Maki T; Department of Neurology, Graduate School of Medicine, Kyoto University, Kyoto, Japan., Kowa H; Division of Neurology, Kobe University Hospital, Kobe, Japan., Tachibana H; Division of Neurology, Kobe University Hospital, Kobe, Japan., Washida K; Department of Neurology, National Cerebral and Cardiovascular Center, Suita, Japan., Kawabata N; Division of Neurology, Yachiyo Hospital, Anjo, Japan., Mizuno T; Department of Neurology, Kyoto Prefectural University of Medicine, Kyoto, Japan., Kanki R; Department of Neurology, Osaka City General Hospital, Osaka, Japan., Sudoh S; Department of Neurology, National Hospital Organization, Utano National Hospital, Kyoto, Japan., Kitaguchi H; Department of Neurology, Kurashiki Central Hospital, Kurashiki, Japan., Shindo K; Department of Neurology, Kurashiki Central Hospital, Kurashiki, Japan., Shindo A; Department of Neurology, Graduate School of Medicine, Mie University, Tsu, Japan., Oka N; Department of Neurology, National Hospital Organization Minami Kyoto Hospital, Joyo, Japan., Yamamoto K; Internal Medicine and Neurology, Nara Midori Clinic, Nara, Japan., Yasuno F; Department of Psychiatry, National Center for Geriatrics and Gerontology, Obu, Japan., Kakuta C; Department of Neurology, National Cerebral and Cardiovascular Center, Suita, Japan., Kakuta R; Department of Data Science, National Cerebral and Cardiovascular Center, Suita, Japan., Yamamoto Y; Department of Molecular Innovation in Lipidemiology, National Cerebral and Cardiovascular Center, Suita, Japan., Hattori Y; Department of Neurology, National Cerebral and Cardiovascular Center, Suita, Japan., Takahashi Y; Department of Neurology, National Cerebral and Cardiovascular Center, Suita, Japan., Nakaoku Y; Department of Neurology, Graduate School of Medicine, Kyoto University, Kyoto, Japan., Tonomura S; Department of Neurology, Graduate School of Medicine, Kyoto University, Kyoto, Japan., Oishi N; Department of Psychiatry, Graduate School of Medicine, Kyoto University, Kyoto, Japan., Aso T; Laboratory for Brain Connectomics Imaging, RIKEN Center for Biosystems Dynamics Research, Kobe, Japan., Taguchi A; Department of Regenerative Medicine Research, Institute of Biomedical Research and Innovation, Kobe, Japan., Kagimura T; Translational Research Center for Medical Innovation, Foundation for Biomedical Research and Innovation at Kobe, Kobe, Japan., Kojima S; Translational Research Center for Medical Innovation, Foundation for Biomedical Research and Innovation at Kobe, Kobe, Japan., Taketsuna M; Translational Research Center for Medical Innovation, Foundation for Biomedical Research and Innovation at Kobe, Kobe, Japan., Tomimoto H; Department of Neurology, Graduate School of Medicine, Mie University, Tsu, Japan., Takahashi R; Department of Neurology, Graduate School of Medicine, Kyoto University, Kyoto, Japan., Fukuyama H; Research and Educational Unit of Leaders for Integrated Medical System, Kyoto University, Kyoto, Japan., Nagatsuka K; Department of Neurology, National Cerebral and Cardiovascular Center, Suita, Japan., Yamamoto H; Department of Data Science, National Cerebral and Cardiovascular Center, Suita, Japan., Fukushima M; Foundation of Learning Health Society Institute, Nagoya, Japan., Ihara M; Department of Neurology, National Cerebral and Cardiovascular Center, Suita, Japan.
Jazyk:	angličtina
Zdroj:	JAMA network open [JAMA Netw Open] 2023 Dec 01; Vol. 6 (12), pp. e2344938. Date of Electronic Publication: 2023 Dec 01.
DOI:	10.1001/jamanetworkopen.2023.44938
Abstrakt:	Importance: Recent evidence indicates the efficacy of β-amyloid immunotherapy for the treatment of Alzheimer disease, highlighting the need to promote β-amyloid removal from the brain. Cilostazol, a selective type 3 phosphodiesterase inhibitor, promotes such clearance by facilitating intramural periarterial drainage. Objective: To determine the safety and efficacy of cilostazol in mild cognitive impairment. Design, Setting, and Participants: The COMCID trial (A Trial of Cilostazol for Prevention of Conversion from Mild Cognitive Impairment to Dementia) was an investigator-initiated, double-blind, phase 2 randomized clinical trial. Adult participants were registered between May 25, 2015, and March 31, 2018, and received placebo or cilostazol for up to 96 weeks. Participants were treated in the National Cerebral and Cardiovascular Center and 14 other regional core hospitals in Japan. Patients with mild cognitive impairment with Mini-Mental State Examination (MMSE) scores of 22 to 28 points (on a scale of 0 to 30, with lower scores indicating greater cognitive impairment) and Clinical Dementia Rating scores of 0.5 points (on a scale of 0, 0.5, 1, 2, and 3, with higher scores indicating more severe dementia) were enrolled. The data were analyzed from May 1, 2020, to December 1, 2020. Interventions: The participants were treated with placebo, 1 tablet twice daily, or cilostazol, 50 mg twice daily, for up to 96 weeks. Main Outcomes and Measures: The primary end point was the change in the total MMSE score from baseline to the final observation. Safety analyses included all adverse events. Results: The full analysis set included 159 patients (66 [41.5%] male; mean [SD] age, 75.6 [5.2] years) who received placebo or cilostazol at least once. There was no statistically significant difference between the placebo and cilostazol groups for the primary outcome. The least-squares mean (SE) changes in the MMSE scores among patients receiving placebo were -0.1 (0.3) at the 24-week visit, -0.8 (0.3) at 48 weeks, -1.2 (0.4) at 72 weeks, and -1.3 (0.4) at 96 weeks. Among those receiving cilostazol, the least-squares mean (SE) changes in MMSE scores were -0.6 (0.3) at 24 weeks, -1.0 (0.3) at 48 weeks, -1.1 (0.4) at 72 weeks, and -1.8 (0.4) at 96 weeks. Two patients (2.5%) in the placebo group and 3 patients (3.8%) in the cilostazol group withdrew owing to adverse effects. There was 1 case of subdural hematoma in the cilostazol group, which may have been related to the cilostazol treatment; the patient was successfully treated surgically. Conclusions and Relevance: In this randomized clinical trial, cilostazol was well tolerated, although it did not prevent cognitive decline. The efficacy of cilostazol should be tested in future trials. Trial Registration: ClinicalTrials.gov Identifier: NCT02491268.
Databáze:	MEDLINE
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