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

The efficacy and safety of hachimijiogan for mild Alzheimer's disease

77

Of the 77 enrollees, 39 patients were placed in the HJG group (15 male and 24 female, average age 75, 6.6 years) and 35 in the control group (15 male and 20 female, average age 76, 6.6 years). The average BMI was 22 in both groups. ADAS-Jcog, a cognitive function assessment, was 14, 5.2 in the HJG group and 14,5.6 in the control group. The IADL, an index of activity, was 5.2, 2.5 in the HJG group and 4.9, 2.2 in the control group. The NPI-Q score, an index of caregiver burden, was 5.6, 7.7 in the HJG group and 4.4, 8.5 in the control group. The Apathy scale (motivation score) was 14, 7.0 in the HJG group and 14, 6.5 in the control group, showing no difference between the two groups. Other factors included hypertension as a complication; 15 in the HJG group and 17 in the control group: Dyslipidemia; 11 in the HJG group and 13 in the control group: Diabetes mellitus; 7 cases in the HJG group and 6 cases in the control group: Acetylcholinesterase inhibitors combined with donepezil; 20 cases in the HJG group and 24 cases in the control group: Concomitant administration of galantamine: 11 cases in the HJG group and 7 cases in the control group: Rivastigmine coadministeration; 8 patients in the HJG group and 4 patients in the control group.

This clinical study started on August 2, 2019 and continued until March 24, 2021. Initially, the study protocol included three sites, but due to a significant delay in case enrollment because of the COVID-19 pandemic an additional 11 sites were added in January 2021. Furthermore, the enrollment deadline was postponed from August 31, 2021 to September 30, 2021. As of the end of September 2021, 77 patients had consented to participate in the study. Three patients dropped out before final enrollment, one discontinued due to interstitial pneumonia and liver injury, and four were excluded because their drug compliance rate was 75% or less. This left the data of 69 patients (34 HJG and 35 controls) available for analysis.

Adverse events were experienced by five patients, one of whom discontinued due to interstitial pneumonia and liver injury.

There was no significant difference between the HJG and control groups in the change in ADAS-Jcog from baseline to 6 months, which was the primary endpoint (1.29; 90% CI, -0.74 to 3.32 P=0.293). However, the change in ADAS-Jcog from baseline to 3 months, a secondary endpoint, a trend was found toward improvement in the HJG group compared to the control group (1.98; 90%CI, -0.17 to 4.14 P=0.130). Furthermore, when a subgroup analysis was performed by sex, a significant between group difference was observed in the change of ADAS-Jcog in female participants at 3 and 6 months (3 months: 3.70; 90%CI, 0.50 to 6.91 P=0.059, 6 months: 2.90; 90%CI, 0.09 to 5.71, P=0.090). For age, the difference in the change from baseline to 3months for participants >=65 was also significant (2.35; 90%CI, 0.01 to 4.68 P=0.099). No significant difference was observed between the HJG and control groups for the other secondary endpoints, IADL, NPI-Q scale, and Apathy scale.

Although our data are not conclusive, they indicate that HJG has an adjuvant effect for acetylcholinesterase inhibitors and that it is effective for delaying the cognitive dysfunction commonly seen in mild Alzheimer disease patients.

Nov. 25, 2022

No

We have no plan

https://jrct.niph.go.jp/latest-detail/jRCTs071190018

Kainuma Mosaburo

Toyama University Hospital

2630 Sugitani,Toyama,Toyama

kainuma@med.u-toyama.ac.jp

Kainuma Mosaburo

Toyama University Hospital

2630 Sugitani,Toyama,Toyama

+81-76-434-7393

kainuma@med.u-toyama.ac.jp

Complete

Aug. 02, 2019

Interventional

randomized controlled trial

open(masking not used)

active control

single assignment

treatment purpose

1) Age:>=50 to <85 years old
2) Mild Alzheimer's disease (MMSE>=21)
3) Using the same dose of Donepezil, Galantamine, or Rivastigmine for more than three months
4) Not taking Memantine
5) Written informed consent

1) Taking Kampo Medicine other than Hachimijiogam
2) Kidney disfunction (eGFR<30mL/min/1.73m2)
3) AST or ALT>100 IU/L
4) Change of drug dosage that could affect the progression cognitive function during the three months
5) Complication with gastric ulcer, bronchial asthma, or epilepsy.
6) Judged by doctors not to be suited for study, such as having serious complications.

Both

mild Alzheimer's disease

One group will take hachimijiogan powder 7.5g/day for 6 months along with their previous standard treatment.The other group will continue the previous standard treatment for 6 months.

Hachimijiogan, mild Alzheimer's disease

ADAS-Jcog

IADL(Instrumental Activity of Daily Life)
Apathy scale
NPI(Nueropsychiatric Inventor)

+81-92-642-5082

June. 10, 2019

none