Guilingji capsule (龟龄集胶囊) for Alzheimer's disease: secondary analysis of a randomized non-inferiority controlled trial

doi:10.19852/j.cnki.jtcm.20230404.006

Abstract

Abstract:

OBJECTIVE: To investigate the effectiveness and safety of Guilingji capsule (龟龄集胶囊, GLJC) in treatment of Alzheimer’s disease (AD) patients with kidney-marrow deficiency pattern (KMDP) compared with gingko extract tablets.
METHODS: This is a secondary analysis of a large-scale multicenter randomized non-inferiority clinical trial. A total of 120 AD patients with KMDP were enrolled in this study. The participants were randomly categorized into two groups: (a) GLJC group (n = 60) and (b) gingko group (n = 60). The GLJC group was treated with GLJC and gingko extract mimetic tablets, whereas the gingko group received gingko extract tablets and mimetic GLJC. The data on the Mini-Mental State Examination (MMSE), Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), Activities of Daily Living (ADL), and Chinese Medicine Symptom Scale (CM-SS) was evaluated at 0, 12, and 24 weeks of treatment. The serum levels of acetylcholine (Ach), acetylcholinesterase (AchE), B-cell lymphoma-2 (Bcl-2), and Bcl-2-associated X protein (Bax) in the participants were measured before and after 24 weeks of treatment. The safety was based on the incidence of adverse events.
RESULTS: Both interventions significantly increased the MMSE scores of the participants and decreased their ADAS-Cog, ADL, and CM-SS scores (P < 0.01). Compared with the gingko group, the GLJC group had a higher effective rate of improvement in the symptoms of “amnesia” and “dull expression and slow thinking” at the 12th week and 24th week (P < 0.05, P < 0.01). In the GLJC group, serum Bcl-2 levels were significantly increased at the 24th week (P < 0.05). Serum Bax and AchE levels of the two groups were significantly decreased at the 24th week (P < 0.01). No treatment-related adverse events were reported in the two groups.
CONCLUSIONS: GLJC is equivalent to the gingko extract tablets in terms of improving cognitive function and the quality of life in AD patients with KMDP and has good clinical efficacy and safety. When it comes to improving TCM symptoms and anti-aging, GLJC is even more advantageous.

Key words: Guilingji capsule, gingko extract tablets, kidney-marrow deficiency pattern, Alzheimer disease, randomized controlled trial

ZHAO Ming, LUO Yimiao, WANG Huichan, CAO Yu, MA Lina, PEI Hui, LI Hao. Guilingji capsule (龟龄集胶囊) for Alzheimer's disease: secondary analysis of a randomized non-inferiority controlled trial[J]. Journal of Traditional Chinese Medicine, 2023, 43(5): 1019-1025.

Figures/Tables 5

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General character	GLJC group (n = 58)	Gingko group (n = 51)
Gender [n (%)]
Male	9 (31.03)	11(42.31)	0.386
Female	20 (68.97)	15 (57.69)	0.386
Age (years, $\bar{x}±s$)	70±6	70±7	0.754
Height (cm, $\bar{x}±s$)	162±7	163±7	0.725
Weight (kg, $\bar{x}±s$)	63±11	62±10	0.808
BMI (kg/m², $\bar{x}±s$)	24±4	23±3	0.567
Blood pressure (mm Hg, $\bar{x}±s$)
Systolic pressure	127±16	133±16	0.171
Diastolic pressure	74±11	75±11	0.792
Heart rate (times/min, $\bar{x}±s$)	68±9	73±11	0.080
Education level [n (%)]
Illiteracy	1 (3.45)	0 (0)	0.069
Primary school	1 (3.45)	4 (15.38)
Secondary school	10 (34.48)	14 (53.85)
College degree or above	17 (58.62)	8 (30.77)
Hypertension [n (%)]
Yes	8 (27.59)	10 (38.46)	0.391
No	21 (72.41)	16 (61.54)	0.391
Coronary disease [n (%)]
Yes	9 (31.03)	5 (19.23)	0.316
No	20 (68.97)	21 (80.77)	0.316
Diabetes [n (%)]
Yes	6 (26.09)	3 (11.54)	0.582
No	23 (73.91)	23 (88.46)	0.582
Hyperlipemia [n (%)]
Yes	1 (3.45)	4 (15.38)	0.286
No	28 (96.55)	22 (84.62)	0.286

General character	GLJC group (n = 58)	Gingko group (n = 51)
Gender [n (%)]
Male	9 (31.03)	11(42.31)	0.386
Female	20 (68.97)	15 (57.69)	0.386
Age (years, $\bar{x}±s$)	70±6	70±7	0.754
Height (cm, $\bar{x}±s$)	162±7	163±7	0.725
Weight (kg, $\bar{x}±s$)	63±11	62±10	0.808
BMI (kg/m², $\bar{x}±s$)	24±4	23±3	0.567
Blood pressure (mm Hg, $\bar{x}±s$)
Systolic pressure	127±16	133±16	0.171
Diastolic pressure	74±11	75±11	0.792
Heart rate (times/min, $\bar{x}±s$)	68±9	73±11	0.080
Education level [n (%)]
Illiteracy	1 (3.45)	0 (0)	0.069
Primary school	1 (3.45)	4 (15.38)
Secondary school	10 (34.48)	14 (53.85)
College degree or above	17 (58.62)	8 (30.77)
Hypertension [n (%)]
Yes	8 (27.59)	10 (38.46)	0.391
No	21 (72.41)	16 (61.54)	0.391
Coronary disease [n (%)]
Yes	9 (31.03)	5 (19.23)	0.316
No	20 (68.97)	21 (80.77)	0.316
Diabetes [n (%)]
Yes	6 (26.09)	3 (11.54)	0.582
No	23 (73.91)	23 (88.46)	0.582
Hyperlipemia [n (%)]
Yes	1 (3.45)	4 (15.38)	0.286
No	28 (96.55)	22 (84.62)	0.286

Time	GLJC group (n = 58)	Gingko group (n = 51)	P value
MMSE
0 week	19.3 ± 3.6	18.3 ± 3.6	0.306
12 weeks	23.1 ± 2.0^a	22.1 ± 3.6^a	0.508
24 weeks	24.3 ± 1.6^a	23.3 ± 2.7^a	0.209
ADAS-cog
0 week	27.6 ± 11.4	30.2 ± 9.2	0.372
12 weeks	16.2 ± 9.4^a	18.5 ± 12.7^a	0.673
24 weeks	13.3 ± 8.7^a	16.4 ± 12.0^a	0.423
ADL
0 week	29.0± 8.3	29.1 ± 8.1	0.691
12 weeks	24.1 ± 6.1^a	25.3 ± 7.6^a	0.647
24 weeks	23.7 ± 5.4^a	24.9 ± 6.83^a	0.798
CM-SS
0 week	20.6 ± 5.9	21.2 ± 7.6	0.726
12 weeks	15.0 ± 4.6^a	15.4 ± 6.3^a	0.966
24 weeks	11.9 ± 4.5^a	13.8 ± 5.8^a	0.327

Time	GLJC group (n = 58)	Gingko group (n = 51)	P value
MMSE
0 week	19.3 ± 3.6	18.3 ± 3.6	0.306
12 weeks	23.1 ± 2.0^a	22.1 ± 3.6^a	0.508
24 weeks	24.3 ± 1.6^a	23.3 ± 2.7^a	0.209
ADAS-cog
0 week	27.6 ± 11.4	30.2 ± 9.2	0.372
12 weeks	16.2 ± 9.4^a	18.5 ± 12.7^a	0.673
24 weeks	13.3 ± 8.7^a	16.4 ± 12.0^a	0.423
ADL
0 week	29.0± 8.3	29.1 ± 8.1	0.691
12 weeks	24.1 ± 6.1^a	25.3 ± 7.6^a	0.647
24 weeks	23.7 ± 5.4^a	24.9 ± 6.83^a	0.798
CM-SS
0 week	20.6 ± 5.9	21.2 ± 7.6	0.726
12 weeks	15.0 ± 4.6^a	15.4 ± 6.3^a	0.966
24 weeks	11.9 ± 4.5^a	13.8 ± 5.8^a	0.327

Group	n	Time	Bax (ng/mL)	Bcl-2 (pg/mL)	Ach (pmol/mL)	AchE(pg/mL)
GLJC	58	0 week	29.10 (19.06, 45.31)	225.45 (154.58, 452.18)	199.46 (198.12, 335.56)	425.78 (357.46, 515.84)
GLJC	58	24 weeks	13.52 (8.32, 22.96)^a	305.03 (165.63, 678.05)^b	197.53 (90.89, 378.62)	375.54 (316.05, 432.10)^a
Gingko	51	0 week	24.52 (14.96, 36.86)	333.43 (185.55, 626.96)	195.12 (94.44, 304.58)	379.78 (333.73, 573.37)
Gingko	51	24 weeks	15.54 (10.44, 21.32)^a	292.95 (172.80, 524.55)	154.07 (98.22, 279.72)	343.06 (289.96, 428.86)^a

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