An exploratory, open-label, randomized, multicenter trial of hachimijiogan for mild Alzheimer’s disease
Background: Alzheimer’s disease (AD) is a progressive neurodegeneration and is the most prevalent form of dementia. Intervention at an early stage is imperative. Although three acetylcholinesterase inhibitors (AChEIs) are currently approved for the treatment of mild AD, they are not sufficiently eff...
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Frontiers Media S.A.
2022-10-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2022.991982/full |
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| author | Mosaburo Kainuma Shinji Ouma Shinobu Kawakatsu Osamu Iritani Ken-Ichiro Yamashita Tomoyuki Ohara Shigeki Hirano Shiro Suda Tadanori Hamano Sotaro Hieda Masaaki Yasui Aoi Yoshiiwa Seiji Shiota Masaya Hironishi Kenji Wada-Isoe Daiki Sasabayashi Sho Yamasaki Masayuki Murata Kouta Funakoshi Kouji Hayashi Norimichi Shirafuji Hirohito Sasaki Yoshinori Kajimoto Yukiko Mori Michio Suzuki Hidefumi Ito Kenjiro Ono Kenjiro Ono Yoshio Tsuboi |
| author_facet | Mosaburo Kainuma Shinji Ouma Shinobu Kawakatsu Osamu Iritani Ken-Ichiro Yamashita Tomoyuki Ohara Shigeki Hirano Shiro Suda Tadanori Hamano Sotaro Hieda Masaaki Yasui Aoi Yoshiiwa Seiji Shiota Masaya Hironishi Kenji Wada-Isoe Daiki Sasabayashi Sho Yamasaki Masayuki Murata Kouta Funakoshi Kouji Hayashi Norimichi Shirafuji Hirohito Sasaki Yoshinori Kajimoto Yukiko Mori Michio Suzuki Hidefumi Ito Kenjiro Ono Kenjiro Ono Yoshio Tsuboi |
| author_sort | Mosaburo Kainuma |
| collection | DOAJ |
| description | Background: Alzheimer’s disease (AD) is a progressive neurodegeneration and is the most prevalent form of dementia. Intervention at an early stage is imperative. Although three acetylcholinesterase inhibitors (AChEIs) are currently approved for the treatment of mild AD, they are not sufficiently effective. Novel treatments for mild AD are of utmost importance.Objective: To assess the effectiveness of hachimijiogan (HJG), a traditional Japanese herbal medicine (Kampo), in the treatment of mild AD.Methods: This exploratory, open-label, randomized, multicenter trial enrolled patients with mild AD whose score on the Mini Mental State Examination (MMSE) was over 21points. All participants had been taking the same dosage of AChEI for more than 3 months. The participants were randomly assigned to an HJG group taking HJG extract 7.5 g/day in addition to AChEI or to a control group treated only with AChEI. The primary outcome was the change from baseline to 6 months post treatment initiation on the Alzheimer’s Disease Assessment Scale-cognitive component- Japanese version(ADAS-Jcog). The secondary outcomes were change from baseline of the Instrumental Activity of Daily Life (IADL), Apathy scale, and Neuropsychiatric Inventory (NPI) -Q score.Results: Among the 77 enrollees, the data of 69(34 HJG and 35 control)were available for analysis. The difference in the change of ADAS-Jcog from baseline to 6 months of the HJG and control groups was 1.29 (90% Confidence interval (CI), −0.74 to 3.32 p = 0.293). In the subgroup analysis, the differences in the change from baseline to 3 and 6 months for women were 3.70 (90% CI ,0.50 to 6.91, p = 0.059) and 2.90 (90% CI,0.09 to 5.71, p = 0.090), respectively. For patients over 65 years, the difference at 3 months was 2.35 (90%CI, 0.01 to 4.68 p = 0.099). No significant differences were found between the HJG and control groups in IADL score, Apathy scale, or NPI-Q score.Conclusion: Although not conclusive, our data indicate that HJG has an adjuvant effect for acetylcholinesterase inhibitors and that it delays the deterioration of the cognitive dysfunction of mild Altzheimer’s disease patients.Clinical Trial Registration:http://clinicaltrials.gov Japan Registry of clinical trials, identifier jRCTs 071190018 |
| first_indexed | 2024-04-12T13:36:49Z |
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| id | doaj.art-c42f211f57f44f7ab0b6bb5eaf4f1a6d |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-04-12T13:36:49Z |
| publishDate | 2022-10-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Pharmacology |
| spelling | doaj.art-c42f211f57f44f7ab0b6bb5eaf4f1a6d2022-12-22T03:30:59ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-10-011310.3389/fphar.2022.991982991982An exploratory, open-label, randomized, multicenter trial of hachimijiogan for mild Alzheimer’s diseaseMosaburo Kainuma0Shinji Ouma1Shinobu Kawakatsu2Osamu Iritani3Ken-Ichiro Yamashita4Tomoyuki Ohara5Shigeki Hirano6Shiro Suda7Tadanori Hamano8Sotaro Hieda9Masaaki Yasui10Aoi Yoshiiwa11Seiji Shiota12Masaya Hironishi13Kenji Wada-Isoe14Daiki Sasabayashi15Sho Yamasaki16Masayuki Murata17Kouta Funakoshi18Kouji Hayashi19Norimichi Shirafuji20Hirohito Sasaki21Yoshinori Kajimoto22Yukiko Mori23Michio Suzuki24Hidefumi Ito25Kenjiro Ono26Kenjiro Ono27Yoshio Tsuboi28Department of Japanese Oriental Medicine, Toyama University Hospital, Toyama, JapanDepartment of Neurology, School of Medicine, Fukuoka University, Fukuoka, JapanDepartment of Neuropsychiatry, Aizu Medical Center, Fukushima Medical University, Aizuwakamatsu, JapanDepartment of Geriatric Medicine, Kanazawa Medical University, Kanazawa, Ishikawa, JapanTranslational Neuroscience Center, Graduate School of Medicine, International University of Health and Welfare, Tochigi, JapanDepartment of Neuropsychiatry, Graduate School of Medical Sciences, Kyushu University, Fukuoka, JapanDepartment of Neurology, Graduate School of Medicine, Chiba University, Chiba, JapanDepartment of Psychiatry, Jichi Medical University, Tochigi, JapanDivision of Neurology, Second Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, Japan0Division of Neurology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan1Department of Neurology, Wakayama Medical University, Wakayama, Japan2Department of General Medicine, Oita UniversityFaculty of Medicine, Oita, Japan2Department of General Medicine, Oita UniversityFaculty of Medicine, Oita, Japan3Department of Internal Medicine, Wakayama Medical University Kihoku Hospital, Wakayama, Japan4Department of Dementia Medicine, Kawasaki Medical School, Okayama, Japan5Department of Neuropsychiatry, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan6Department of General Internal Medicine, Kyushu University Hospital, Fukuoka, Japan6Department of General Internal Medicine, Kyushu University Hospital, Fukuoka, Japan7Center for Clinical and Translational Research, Kyushu University Hospital, Fukuoka, Japan8Department of Rehabilitation, Fukui Health Science University, Fukui, JapanDivision of Neurology, Second Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, JapanDivision of Neurology, Second Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, Japan3Department of Internal Medicine, Wakayama Medical University Kihoku Hospital, Wakayama, Japan0Division of Neurology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan5Department of Neuropsychiatry, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan1Department of Neurology, Wakayama Medical University, Wakayama, Japan0Division of Neurology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan9Department of Neurology, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Ishikawa, JapanDepartment of Neurology, School of Medicine, Fukuoka University, Fukuoka, JapanBackground: Alzheimer’s disease (AD) is a progressive neurodegeneration and is the most prevalent form of dementia. Intervention at an early stage is imperative. Although three acetylcholinesterase inhibitors (AChEIs) are currently approved for the treatment of mild AD, they are not sufficiently effective. Novel treatments for mild AD are of utmost importance.Objective: To assess the effectiveness of hachimijiogan (HJG), a traditional Japanese herbal medicine (Kampo), in the treatment of mild AD.Methods: This exploratory, open-label, randomized, multicenter trial enrolled patients with mild AD whose score on the Mini Mental State Examination (MMSE) was over 21points. All participants had been taking the same dosage of AChEI for more than 3 months. The participants were randomly assigned to an HJG group taking HJG extract 7.5 g/day in addition to AChEI or to a control group treated only with AChEI. The primary outcome was the change from baseline to 6 months post treatment initiation on the Alzheimer’s Disease Assessment Scale-cognitive component- Japanese version(ADAS-Jcog). The secondary outcomes were change from baseline of the Instrumental Activity of Daily Life (IADL), Apathy scale, and Neuropsychiatric Inventory (NPI) -Q score.Results: Among the 77 enrollees, the data of 69(34 HJG and 35 control)were available for analysis. The difference in the change of ADAS-Jcog from baseline to 6 months of the HJG and control groups was 1.29 (90% Confidence interval (CI), −0.74 to 3.32 p = 0.293). In the subgroup analysis, the differences in the change from baseline to 3 and 6 months for women were 3.70 (90% CI ,0.50 to 6.91, p = 0.059) and 2.90 (90% CI,0.09 to 5.71, p = 0.090), respectively. For patients over 65 years, the difference at 3 months was 2.35 (90%CI, 0.01 to 4.68 p = 0.099). No significant differences were found between the HJG and control groups in IADL score, Apathy scale, or NPI-Q score.Conclusion: Although not conclusive, our data indicate that HJG has an adjuvant effect for acetylcholinesterase inhibitors and that it delays the deterioration of the cognitive dysfunction of mild Altzheimer’s disease patients.Clinical Trial Registration:http://clinicaltrials.gov Japan Registry of clinical trials, identifier jRCTs 071190018https://www.frontiersin.org/articles/10.3389/fphar.2022.991982/fullAlzheimer’s diseasehachimijioganADAS‐JcogKampo medicinecognitive dysfunction |
| spellingShingle | Mosaburo Kainuma Shinji Ouma Shinobu Kawakatsu Osamu Iritani Ken-Ichiro Yamashita Tomoyuki Ohara Shigeki Hirano Shiro Suda Tadanori Hamano Sotaro Hieda Masaaki Yasui Aoi Yoshiiwa Seiji Shiota Masaya Hironishi Kenji Wada-Isoe Daiki Sasabayashi Sho Yamasaki Masayuki Murata Kouta Funakoshi Kouji Hayashi Norimichi Shirafuji Hirohito Sasaki Yoshinori Kajimoto Yukiko Mori Michio Suzuki Hidefumi Ito Kenjiro Ono Kenjiro Ono Yoshio Tsuboi An exploratory, open-label, randomized, multicenter trial of hachimijiogan for mild Alzheimer’s disease Frontiers in Pharmacology Alzheimer’s disease hachimijiogan ADAS‐Jcog Kampo medicine cognitive dysfunction |
| title | An exploratory, open-label, randomized, multicenter trial of hachimijiogan for mild Alzheimer’s disease |
| title_full | An exploratory, open-label, randomized, multicenter trial of hachimijiogan for mild Alzheimer’s disease |
| title_fullStr | An exploratory, open-label, randomized, multicenter trial of hachimijiogan for mild Alzheimer’s disease |
| title_full_unstemmed | An exploratory, open-label, randomized, multicenter trial of hachimijiogan for mild Alzheimer’s disease |
| title_short | An exploratory, open-label, randomized, multicenter trial of hachimijiogan for mild Alzheimer’s disease |
| title_sort | exploratory open label randomized multicenter trial of hachimijiogan for mild alzheimer s disease |
| topic | Alzheimer’s disease hachimijiogan ADAS‐Jcog Kampo medicine cognitive dysfunction |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2022.991982/full |
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