[국내논문]The Effect of Adding Kami-guibi-tang to Acetylcholinesterase Inhibitor Treatment on the Cognitive Function of Mild Alzheimer's Disease Patients: Study Protocol of a Randomized, Placebo-Controlled, Double-Blind Pilot Trial원문보기
Yang, Seung-bo
(Dept. of Korean Internal Medicine, College of Korean Medicine, Gachon University)
,
Kim, Ha-ri
(Stroke and Neurological Disorders Center, Kyung Hee University Hospital at Gangdong)
,
Shin, Hee-yeon
(Stroke and Neurological Disorders Center, Kyung Hee University Hospital at Gangdong)
,
Kim, Jeong-hwa
(Stroke and Neurological Disorders Center, Kyung Hee University Hospital at Gangdong)
,
Lee, Chang-woo
(Dept. of Clinical Korean Medicine, Graduate School, Kyung Hee University)
,
Jahng, Geon-ho
(Dept. of Radiology, Kyung Hee University Hospital at Gangdong, College of Medicine, Kyung Hee University)
,
Park, Seong-uk
(Stroke and Neurological Disorders Center, Kyung Hee University Hospital at Gangdong)
,
Ko, Chang-nam
(Stroke and Neurological Disorders Center, Kyung Hee University Hospital at Gangdong)
,
Park, Jung-mi
(Stroke and Neurological Disorders Center, Kyung Hee University Hospital at Gangdong)
Background: Alzheimer's disease (AD) is a chronic neurodegenerative disease that causes disorientation, mood swings, problems with language, and difficulty remembering recent events. Acetylcholinesterase inhibitors (AchEIs) and memantine have been used to slow the course of the disease, but they can...
Background: Alzheimer's disease (AD) is a chronic neurodegenerative disease that causes disorientation, mood swings, problems with language, and difficulty remembering recent events. Acetylcholinesterase inhibitors (AchEIs) and memantine have been used to slow the course of the disease, but they can neither modify its progression nor prevent disease onset. Previous studies have suggested that Kami-guibi-tang (KGT) could be beneficial for supporting cognitive function in AD patients, but few clinical trials have been published. This pilot study aimed to evaluate the effect of KGT in improving cognitive function in AD patients. Methods: The study will be a randomized, placebo-controlled, double-blind, single-center trial conducted using subjects diagnosed with mild AD by neurologists. Study subjects will be randomly assigned to either a treatment or control group. The treatment group will receive KGT granules for 24 weeks, while the control group will receive placebo granules. AchEI administration will be maintained in both groups during the entirety of the study. Subjects will be assessed using the following exams: the Seoul Neuropsychologic Screening Battery (SNSB) for cognitive function; brain magnetic resonance imaging (MRI) for brain metabolite, neurotransmitter, and cerebral blood flow (CBF) measurements; the Korean version of Quality of Life-Alzheimer's Disease (KQol-AD) for quality of life; the Caregiver-Administered Neuropsychiatric Inventory (CGA-NPI) for neurobehavioral symptoms; blood tests for amyloid and tau proteins and general blood parameters; and electrocardiography (ECG) before and after taking the medication. Discussion: Our findings will provide insight into the feasibility of large-scale trials to consolidate evidence for the efficacy of KGT for dementia treatment. Registration ID in CRIS: KCT0002904 (Clinical Research Information Service of the Republic of Korea).
Background: Alzheimer's disease (AD) is a chronic neurodegenerative disease that causes disorientation, mood swings, problems with language, and difficulty remembering recent events. Acetylcholinesterase inhibitors (AchEIs) and memantine have been used to slow the course of the disease, but they can neither modify its progression nor prevent disease onset. Previous studies have suggested that Kami-guibi-tang (KGT) could be beneficial for supporting cognitive function in AD patients, but few clinical trials have been published. This pilot study aimed to evaluate the effect of KGT in improving cognitive function in AD patients. Methods: The study will be a randomized, placebo-controlled, double-blind, single-center trial conducted using subjects diagnosed with mild AD by neurologists. Study subjects will be randomly assigned to either a treatment or control group. The treatment group will receive KGT granules for 24 weeks, while the control group will receive placebo granules. AchEI administration will be maintained in both groups during the entirety of the study. Subjects will be assessed using the following exams: the Seoul Neuropsychologic Screening Battery (SNSB) for cognitive function; brain magnetic resonance imaging (MRI) for brain metabolite, neurotransmitter, and cerebral blood flow (CBF) measurements; the Korean version of Quality of Life-Alzheimer's Disease (KQol-AD) for quality of life; the Caregiver-Administered Neuropsychiatric Inventory (CGA-NPI) for neurobehavioral symptoms; blood tests for amyloid and tau proteins and general blood parameters; and electrocardiography (ECG) before and after taking the medication. Discussion: Our findings will provide insight into the feasibility of large-scale trials to consolidate evidence for the efficacy of KGT for dementia treatment. Registration ID in CRIS: KCT0002904 (Clinical Research Information Service of the Republic of Korea).
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문제 정의
Although previous studies have suggested that KGT may be beneficial for improving cognitive function in AD subjects, few randomized controlled trials have been conducted. This manuscript describes the protocol of a pilot randomized controlled trial designed to evaluate the effect of adding KGT to AchEI treatment on the cognitive function of AD patients, and its influence on neuroimaging and neurochemical biomarkers.
제안 방법
This study was designed as a randomized, placebocontrolled, parallel-group, double-blind, single-center trial to be conducted at Kyung Hee University Hospital at Gangdong, Seoul, Korea, from January 1st, 2018 to November 30th, 2019. The flow chart of the study design is shown in Fig.
- Since there are no absolute values of the K-MMSE (Korean version of the Mini-Mental State Examination), GDS (Global Deterioration Scale), or CDR validated for the diagnosis of mild AD, different criteria are applied in different clinical studies. This study includes subjects who are regarded as having mild AD, as assessed witthe CDR, among patients diagnosed with AD by neurologists using NINCDS-ADRDA.
A random, computer-generated, allocation list will be generated using SPSS version 18 by an assigned researcher not involved in the cognitive assessments. The subjects will be randomly allocated to either the treatment or control group in a 1:1 ratio using a block randomization method with a block size of four. Subjects, the assessor, the clinical trial pharmacist, and the researcher will be blinded to allocations throughout the course of the study.
The treatment and placebo granules will be distributed to subjects by an independent clinical pharmacist. The subjects will be instructed to dissolve the granules in hot water, stir well, and drink the solution three times per day, 30 minutes after meals, for 24 consecutive weeks. A reminder phone call will be made every week in order to promote adherence to taking the study medication.
The full version of the SNSB-II will be administered at baseline and after 24 weeks of KGT or placebo treatment to evaluate the effect of KGT on cognitive function. The estimated completion time of the whole battery is 1.
All subjects will undergo brain MRI at baseline and after 24 weeks of KGT or placebo treatment to measure changes in metabolites and neurotransmitter levels, cerebral blood flow, and tissue volume, and to evaluate brain abnormalities.
Safety assessments will be conducted using laboratory tests and electrocardiography (ECG). A blood test, measuring levels of AST/ALT, glucose, BUN (blood urea nitrogen), creatinine, Na, K, Cl, cholesterol, LDH, and CPK, will be performed at baseline and after 12 and 24 weeks of treatment. ECG will be performed at baseline and after 24 weeks of KGT or placebo treatment.
This clinical trial is a pilot study to examine the feasibility of a full randomized clinical trial of KGT, and to determine the sample magnitude required for large-scale studies. To our knowledge, no prior study has investigated the effect of KGT on mild AD.
In this study, extensive assessment tools will be used to evaluate the effects of KGT and the mechanisms of any detected effects. Instruments such as the K-MMSE, SNSB, KQoL-AD, and CGA-NPI will be used to assess cognitive function.
This pilot study will constitute a rigorous clinical analysis of KGT for the treatment of mild AD, and will provide evidence for the effect of adding KGT to AchEI treatment. Our extensive assessment of various biomarkers will provide information regarding the mechanisms underlying any effects of KGT on disease progression.
대상 데이터
Normally, 10 to 20 subjects in each group should be sufficient to implement a pilot study. In this study, we plan to perform a statistical analysis using a total of 30 subjects, with 15 in each group. Allowing for a maximum dropout rate of 20%, the desired sample size for this pilot study is 38 subjects, with 19 in each group.
In this study, we plan to perform a statistical analysis using a total of 30 subjects, with 15 in each group. Allowing for a maximum dropout rate of 20%, the desired sample size for this pilot study is 38 subjects, with 19 in each group.
데이터처리
A regression analysis will be used to estimate the relationship between changes in MRI measurements and changes in blood tests. The two-sample t-test will be applied to compare changes in MRI measurements between the study group and the placebo group, using age and genotype as covariates.
이론/모형
A total of at least 38 subjects will be recruited through advertisements and referrals. Candidates with complaints of impaired memory who are aged 55-90 years will be screened using the inclusion /exclusion criteria, K-MMSE, and Korean Dementia Screening Questionnaire (KDSQ). Potentially eligible subjects will undergo the SNSB, and those who are diagnosed with mild AD by a neurologist will be included in the trial.
All statistical analyses will be performed using SPSS for Windows. The data will be analyzed according to the intentionto-treat (ITT) principle and per protocol principle. We will adjust for missing data using the last observation carried forward (LOCF) principle to obtain a complete database.
성능/효과
(3) Subjects who have received cognitive-related medication, including AChEIs such as donepezil, rivastigmine, and galantamine, and remained stable condition without any adverse events. Cognitiverelated medications include cerebral blood flow improvement agents and other brain nutrients that affect brain cognition, such as gliatilin, gliatamin, ginexin, and tanamine.
(3) Comparisons of changes in MRI measurements (brain metabolites, neurotransmitters, cerebral blood flow) between treatment and placebo groups using age and genotype (ApoE) as covariates.
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