Clinical Study of GKT in Diabetes Related Dementia

Clinical Study of Ginkgo Biloba Ketone Ester Tablets in Diabetes Related Dementia

Recently a new clinical dementia subgroup based on brain imaging, called "diabetes related dementia (DrD)". DrD, unlike Alzheimer's disease and vascular dementia, is considered a "controllable" or "modifiable" form of dementia. However, there is currently a lack of corresponding treatment measures. Ginkgo biloba ketone ester tablets are extracts of Ginkgo biloba leaves. Previous studies have shown that they can increase cerebral blood flow, reduce cerebrovascular resistance, improve cerebral circulation, and are beneficial for the treatment of cognitive impairment. This project intends to explore the role of ginkgo ketoester tablets in diabetes related dementia through a multicenter randomized double-blind controlled clinical study.

Study Overview

• Status: Not yet recruiting
• Conditions: Dementia
• Intervention / Treatment: Drug: Ginkgo Ketone Ester Tablets; Drug: placebo

Detailed Description

This study was divided into two treatment groups: the experimental group and the control group. 370 type 2 diabetes patients with mild cognitive impairmentpatients were randomly selected and assigned to the experimental group of 185 patients and the control group of 185 patients in a 1:1 equal amount. Experimental group: Ginkgo biloba ketone ester tablets combined with conventional hypoglycemic treatment group, the usage is Ginkgo biloba ketone ester tablets (Styron), taken orally, 3 times a day, 0.5g each time, and continuously administered for 6 months. Control group: conventional hypoglycemic treatment group. The Montreal Cognitive Assessment Basic (MoCA-B) was used for the detection of cognitive dysfunction. Neuropsychological testing of cognitive function was conducted using Alzheimer's Disease Assessment Scale - Cognitive Scale (ADAS-cog), Auditory Word Learning Test (AVLT-H);Assessment of Daily Living Ability - Functional Activity Questionnaire (FAQ);Shape Connection Test A and B and Symbolic Digital Form Test (SDMT).Collect patients' blood, and detect C-reactive protein, interleukin-6, oxidative stress, ApoE4 genotype, phosphorylated tau protein, irisin, β- Amyloid protein before and after the experiment.Detect changes in ankle brachial pulse wave conduction velocity (baPWV)/and ankle brachial blood pressure index (ABI) of patients before and after the experiment.

• Study Type: Interventional
• Enrollment (Estimated): 370
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Type 2 diabetes with mild cognitive impairment patients aged 65 years or above;
2. Able to cooperate in completing cognitive function testing;
3. Patients who can swallow pills
4. No previous history of stroke，cerebral thrombosis, etc

Exclusion Criteria:

1. Type 1 diabetes;
2. Acute cerebral infarction and myocardial infarction within 3 months;
3. Severe liver and kidney dysfunction;
4. Late stage malignant tumors;
5. Thyroid dysfunction；
6. Brain injury and cerebral hemorrhage within 3 months；
7. Folic acid and/or vitamin B12 deficiency
8. Patients who are currently using thrombin inhibitors, defibrillators (with unclear efficacy in ischemic stroke and increased risk of bleeding), antiplatelet drugs, blood activating and stasis resolving agents, and other ginkgo biloba leaf preparations (as they may affect the evaluation of the therapeutic effect of ginkgo biloba ester tablets in this trial), as well as other trial medications.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ginkgo Ketone Ester Tablets Treatment Group; Ginkgo Ketone Ester Tablets (Styron), taken orally, 3 times a day, 0.5g each time, combined with conventional hypoglycemic therapy continuously administered for 6 months	Drug: Ginkgo Ketone Ester Tablets; Ginkgo Ketone Ester Tablets taken orally, 3 times a day, 0.5g each time, combined with conventional hypoglycemic treatment for six months; Other Names: Test group
Placebo Comparator: control group; placebo combined with conventional hypoglycemic therapy for 6 months	Drug: placebo; placebo, taken orally, 3 times a day, 0.5g each time, combined with conventional hypoglycemic treatment for six months; Other Names: Control group

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cognitive function testing	Alzheimer's Disease Assessment Scale-Cognitive section (0-70), the higher the score, the more severe the cognitive impairment	six months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Memory function assessment	Auditory Word Learning Test (AVLT-H),the lower the score, the more severe the cognitive impairment	six months
Assessment of daily living ability	Functional Activity Questionnaire (FAQ)S,the higher the score, the more severe the cognitive impairment	six months
Perform functional evaluation	Shape Connection Test A and B (STT-A&B)，the higher the score, the more severe the cognitive impairment	six months
Attention assessment	Symbolic Digital Form Test (SDMT)，the lower the score, the more severe the cognitive impairment	six months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Concentration of C-reactive protein	Human CRP(C-Reactive Protein) ELISA Kit for detecting C-reactive protein concentration (mg/L )in serum	six months
Rate of arteriosclerosis in the large and middle arterial systems	ankle brachial pulse wave conduction velocity (m/s )detected by Arteriosclerosis tester	six months
Rate of arterial blockage in limbs	ankle brachial blood pressure index (ABI) measures ankle blood pressure and upper arm brachial artery blood pressure through ankle brachial index instrument	six months
Concentration of interleukin-6	interleukin-6(IL-6) in serum detected by interleukin-6 ELISA Kit	six months
Concentration of phosphorylation (p) - tau217	Plasma phosphorylation (p) - tau217detected by P-Tau217 detection kit	six months
Concentration of Amyloid protein Aβ 42/40	Plasma Amyloid protein Aβ 42/40 detected by Aβ 42/40 detection kit	six months
Participants with ApoE4 genotype	ApoE4 genotype detected by ApoE4 genotype kit	six months
Concentration of antioxidant enzyme activity	Detection of glutathione peroxidase in serum	six months
Concentration of oxidative stress	Free radical detection in serum	six months
Concentration of irisin	Plasma irisin concentration detected by irisin ELISA kit	six months

Collaborators and Investigators

• Sponsor: Shanghai 10th People's Hospital

Publications and helpful links

General Publications

• Fukazawa R, Hanyu H, Sato T, Shimizu S, Koyama S, Kanetaka H, Sakurai H, Iwamoto T. Subgroups of Alzheimer's disease associated with diabetes mellitus based on brain imaging. Dement Geriatr Cogn Disord. 2013;35(5-6):280-90. doi: 10.1159/000348407. Epub 2013 Apr 13.
• Hanyu H, Hirose D, Fukasawa R, Hatanaka H, Namioka N, Sakurai H. Guidelines for the Clinical Diagnosis of Diabetes Mellitus-Related Dementia. J Am Geriatr Soc. 2015 Aug;63(8):1721-3. doi: 10.1111/jgs.13581. No abstract available.
• Verdile G, Fuller SJ, Martins RN. The role of type 2 diabetes in neurodegeneration. Neurobiol Dis. 2015 Dec;84:22-38. doi: 10.1016/j.nbd.2015.04.008. Epub 2015 Apr 26.
• Fukasawa R, Hanyu H, Namioka N, Hatanaka H, Sato T, Sakurai H. Elevated inflammatory markers in diabetes-related dementia. Geriatr Gerontol Int. 2014 Jan;14(1):229-31. doi: 10.1111/ggi.12140. No abstract available.
• Hatanaka H, Hanyu H, Fukasawa R, Sato T, Shimizu S, Sakurai H. Peripheral oxidative stress markers in diabetes-related dementia. Geriatr Gerontol Int. 2016 Dec;16(12):1312-1318. doi: 10.1111/ggi.12645. Epub 2015 Nov 4.
• Hirose D, Hanyu H, Fukasawa R, Hatanaka H, Namioka N, Sakurai H. Frailty in diabetes-related dementia. Geriatr Gerontol Int. 2016 May;16(5):653-5. doi: 10.1111/ggi.12566. No abstract available.

Study record dates

Study Major Dates

• Study Start (Estimated): December 1, 2023
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): June 30, 2026

Study Registration Dates

• First Submitted: April 10, 2023
• First Submitted That Met QC Criteria: May 2, 2023
• First Posted (Actual): May 12, 2023

Study Record Updates

• Last Update Posted (Estimated): November 13, 2023
• Last Update Submitted That Met QC Criteria: November 9, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Dementia
• Other Study ID Numbers: GKT

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No