Li I-Chen, Chang Han-Hsin, Lin Chuan-Han, Chen Wan-Ping, Lu Tsung-Han, Lee Li-Ya, Chen Yu-Wen, Chen Yen-Po, Chen Chin-Chu, Lin David Pei-Cheng
Biotech Research Institute, Grape King Bio Ltd., Taoyuan City, Taiwan.
Department of Nutrition, Chung Shan Medical University, Taichung City, Taiwan.
Front Aging Neurosci. 2020 Jun 3;12:155. doi: 10.3389/fnagi.2020.00155. eCollection 2020.
To investigate the efficacy and safety of three mycelia (EAHE) capsules (350 mg/capsule; containing 5 mg/g erinacine A active ingredient) per day for the treatment of patients with mild Alzheimer's Disease (AD).
This study comprised a 3-week no-drug screening period, followed by a 49-week double-blind treatment period with 2-parallel groups in which eligible patients were randomized to either three 5 mg/g EAHE mycelia capsules per day or identical appearing placebo capsules. Cognitive assessments, ophthalmic examinations, biomarker collection, and neuroimaging were followed throughout the study period.
After 49 weeks of EAHE intervention, a significant decrease in Cognitive Abilities Screening Instrument score was noted in the placebo group, a significant improvement in Mini-Mental State Examination score was observed in the EAHE group and a significant Instrumental Activities of Daily Living score difference were found between the two groups. In addition, EAHE group achieved a significantly better contrast sensitivity when compared to the placebo group. Moreover, only the placebo group observed significantly lowered biomarkers such as calcium, albumin, apolipoprotein E4, hemoglobin, and brain-derived neurotrophic factor and significantly elevated alpha1-antichymotrypsin and amyloid-beta peptide 1-40 over the study period. Using diffusion tensor imaging, the mean apparent diffusion coefficient (ADC) values from the arcuate fasciculus region in the dominant hemisphere significantly increased in the placebo group while no significant difference was found in the EAHE group in comparison to their baselines. Moreover, ADC values from the parahippocampal cingulum region in the dominant hemisphere significantly decreased in the EAHE group whereas no significant difference was found in the placebo group when compared to their baselines. Lastly, except for four subjects who dropped out of the study due to abdominal discomfort, nausea, and skin rash, no other adverse events were reported.
Three 350 mg/g EAHE capsules intervention for 49 weeks demonstrated higher CASI, MMSE, and IADL scores and achieved a better contrast sensitivity in patients with mild AD when compared to the placebo group, suggesting that EAHE is safe, well-tolerated, and may be important in achieving neurocognitive benefits.
ClinicalTrials.gov, identifier NCT04065061.
研究每日服用三粒菌丝体（EAHE）胶囊（350毫克/粒；每克含5毫克厄立纳辛A活性成分）治疗轻度阿尔茨海默病（AD）患者的疗效和安全性。
本研究包括为期3周的无药物筛查期，随后是为期49周的双盲治疗期，分为2个平行组，符合条件的患者被随机分为每日服用三粒每克含5毫克EAHE菌丝体胶囊组或外观相同的安慰剂胶囊组。在整个研究期间进行认知评估、眼科检查、生物标志物采集和神经影像学检查。
EAHE干预49周后，安慰剂组认知能力筛查工具评分显著下降，EAHE组简易精神状态检查表评分显著改善，两组间日常生活活动能力量表评分存在显著差异。此外，与安慰剂组相比，EAHE组的对比敏感度显著更好。此外，在研究期间，只有安慰剂组观察到钙、白蛋白、载脂蛋白E4、血红蛋白和脑源性神经营养因子等生物标志物显著降低，α1-抗糜蛋白酶和淀粉样β肽1-40显著升高。使用扩散张量成像，安慰剂组优势半球弓状束区域的平均表观扩散系数（ADC）值相对于基线显著增加，而EAHE组与基线相比无显著差异。此外，EAHE组优势半球海马旁扣带区域的ADC值相对于基线显著降低，而安慰剂组与基线相比无显著差异。最后，除4名因腹部不适、恶心和皮疹退出研究的受试者外，未报告其他不良事件。
与安慰剂组相比，每日服用三粒350毫克/克EAHE胶囊干预49周在轻度AD患者中显示出更高的CASI、MMSE和IADL评分，并具有更好的对比敏感度，表明EAHE安全、耐受性良好，可能对实现神经认知益处具有重要意义。
ClinicalTrials.gov，标识符NCT04065061。
