The efficacy and safety of hachimijiogan for mild Alzheimer disease in an exploratory, open standard treatment controlled, randomized allocation, multicenter trial

Abstract

Background: Dementia among the Japanese aged 65 years or over population is estimated to approach about 700 million cases by 2025, and a corresponding rapid increase in Alzheimer disease (AD) can also be expected. The ballooning number of dementia patients, including AD, is creating major medical and social challenges. At present, only 3 drugs are recognized for the treatment of mild AD, and these are only used to alleviate symptoms. Although new therapies are needed to treat mild AD, insufficient development of disease-modifying drugs is being done. Methods/Design: The aim of this exploratory, open standard, treatment-controlled, randomized allocation, multicenter trial is to determine the efficacy of the traditional Japanese Kampo medicine hachimijiogan (HJG) on the cognitive dysfunction of mild AD. Eighty-six patients with AD diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 and as mild AD according to the Mini Mental State Examination (MMSE ≥21) will be included. All will already have been taking the same dose of Donepezil, Galantamine, or Rivastigmine for more than 3 months. The patients will be randomly assigned to receive additional treatment with HJG or to continue mild AD treatment without additional HJG. The primary endpoint is the change from baseline of the Alzheimer's Disease Assessment Scale-cognitive component- Japanese version (ADAS-Jcog). ADAS-Jcog is a useful index for detecting change over time that investigates memory and visuospatial cognition injury from the early stage. The secondary endpoints are the changes from baseline of the Instrumental Activity of Daily Life, Apathy scale, and Nueropsychiatric Inventory scores. In this protocol, we will examine the Geriatric depression scale and do Metabolome analysis as exploratory endpoints. The recruitment period will be from August 2019 to July 2021. Discussion: This is the first trial of Kampo medicine designed to examine the efficacy of HJG for the cognitive dysfunction of patients with mild AD. Trial registration: This trial was registered on the Japan Registry of Clinical trials on 2 August 2, 2019 (jRCTs 071190018).

Metabolic changes in the plasma of mild Alzheimer’s disease patients treated with Hachimijiogan

“…The data analyzed in this study was from our previous open-label, randomized, multicenter, control trials ( Kainuma et al, 2020 ; Kainuma et al, 2022 ).…”

An exploratory, open-label, randomized, multicenter trial of hachimijiogan for mild Alzheimer’s disease

“…This 24-week, open-label, randomized, multicenter trial was conducted at 14 sites in Japan between 2 August 2019 and 31 March 2022. We initially planned to recruit participants at three institutes according to the published protocol (Kainuma et al, 2020). However, because of the COVID-19 pandemic, the recruitment was delayed, so from January 2021 we were able to add 11 institutes.…”

Kampo Medicine for Older People: A Review

“…Currently, an exploratory, open-label standard treatment-controlled, randomized allocation, multicenter trial is underway to investigate the efficacy and safety of hachimijiogan in the treatment of mild AD and is expected to further clarify the effect of hachimijiogan in dementia [12].…”