Multicenter RCT of Eye-Brain Imaging in Diabetes Neurovascular Coupling

NCT ID: NCT06813274

Last Updated: 2025-09-26

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 160 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2026-01-01
• Study Completion Date: 2026-12-01

Brief Summary

This study intends to take the critical pathological mechanism of diabetic neurovascular coupling injury (NCI) as the starting point and utilize multi-modal imaging (MMI) technology of the eyes and brain as a means to conduct in-depth, integrated, and interdisciplinary research with Traditional Chinese Medicine (TCM) syndrome studies. The aim is to establish diagnostic and therapeutic standards for diabetic NCI, based on Eye-Brain Multimodal Imaging technology, providing objective and quantitative evidence for early disease diagnosis and therapeutic effect evaluation. Simultaneously, investigators will conduct multicenter, randomized, placebo-controlled, double-blind clinical trials to systematically investigate the clinical efficacy and safety of Tangshen'an Granule in preventing and treating diabetic NCI. By obtaining high-quality evidence-based data on TCM, this study aims to enhance the level of prevention and treatment with TCM and clinical service capabilities, thereby providing new ideas and directions for research.

Detailed Description

Diabetes mellitus(DM) is a prevalent condition that often leads to neurovascular coupling impairment (NCI), which has been shown to be intimately associated with diabetic retinopathy and cognitive decline. Given the critical need for early diagnosis and effective treatment, eye-brain multimodal imaging(MMI) technology has emerged as a promising tool in this field. This study focuses on establishing a comprehensive and standardized approach for diagnosing and treating diabetic NCI through the utilization of eye-brain MMI technology accompanied by assessing the effectiveness and potential therapeutic benefits of the traditional Chinese medicine compound, Tangshen'an Granule, in the management of diabetic NCI.

A pool of standard diagnostic and therapeutic entries for diabetic NCI syndromes using eye-brain MMI technology is planned to be established through database retrieval and refined by expert questionnaire surveys to formulate the relevant standards. A multicenter, randomized, double-blind, placebo-controlled clinical evaluation study of Tangshen'an Granules in treating diabetic NCI (kidney deficiency and blood stasis syndrome) patients from specific hospitals will be conducted. Diagnostic criteria involve diabetes diagnosis and specific requirements of multiple eye-brain imaging and cognitive assessment tools. Eligibility criteria include inclusion and exclusion conditions. Randomization and blinding are properly implemented. The intervention includes basic therapy with different drug administrations in the experimental and control groups. The trial lasts 24 weeks. Primary outcomes are evaluated by various eye-brain imaging and cognitive assessment means. Secondary outcomes involve TCM symptom scores, glycemic indicators, and quality of life questionnaire. Safety indicators are monitored. Data is analyzed using Intent-To-Treat (ITT) analysis.

The study protocol has been approved by the Ethics Committee of the Hospital of Chengdu University of Traditional Chinese Medicine(ethical approval number:2023KL-056). Informed consent is planned to be obtained from all participants. The study results will be reported in academic meetings and peer-reviewed journals to promote the development of diagnostic and treatment standards for diabetic NCI.

Conditions

Diabetes Mellitus; Diabetic Retinopathy; Cognitive Impairment; Neurovascular Coupling

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Intervention Group

Participants assigned to the experimental group will receive hypoglycemic treatment, accompanied by the administration of Tangshen'an Granules, Ginkgo Leaf Tablets, and Mecobalamin Capsules.

Group Type: EXPERIMENTAL

hypoglycemic treatment

Intervention Type: DRUG

The diabetes management adheres to the "The 2025 Guidelines for Standards of Diabetes Care" issued by the American Diabetes Association (ADA).

Tangshen'an Granules

Intervention Type: DRUG

Tangshen'an Granules comprises a meticulously blended mix of Astragalus, Prepared Rehmannia Root, Dodder Seed, Kudzu Root, Millettia Speciosa Champ, Salviae Miltiorrhizae Radix et Rhizoma, Poria Cocos, and Polygala Tenuifolia. Tangshen'an Granules is administered at a dosage of 9g, dissolved in boiling water, and taken three times daily.

Ginkgo Leaf Tablets

Intervention Type: DRUG

The primary active ingredients of Ginkgo Leaf Tablets are ginkgo flavonoid glycosides and terpene lactones. The prescribed oral dosage is one tablet each time, administered three times a day.

Mecobalamin Tablets

Intervention Type: DRUG

Mecobalamin Tablets primarily contain mecobalamin, which is a coenzyme-active form of vitamin B12. The prescribed oral dosage is 0.5mg, administered three times a day.

Control Group

Participants assigned to the control group will receive hypoglycemic treatment, accompanied by placebo, Ginkgo Leaf Tablets, and Mecobalamin Tablets.

Group Type: PLACEBO_COMPARATOR

hypoglycemic treatment

Intervention Type: DRUG

The diabetes management adheres to the "The 2025 Guidelines for Standards of Diabetes Care" issued by the American Diabetes Association (ADA).

Ginkgo Leaf Tablets

Intervention Type: DRUG

The primary active ingredients of Ginkgo Leaf Tablets are ginkgo flavonoid glycosides and terpene lactones. The prescribed oral dosage is one tablet each time, administered three times a day.

Mecobalamin Tablets

Intervention Type: DRUG

Mecobalamin Tablets primarily contain mecobalamin, which is a coenzyme-active form of vitamin B12. The prescribed oral dosage is 0.5mg, administered three times a day.

placebo

Intervention Type: DRUG

The placebo contains 10% of the active ingredients in Tangshen'an Granules, formulated by controlling the concentration to mimic Tangshen'an Granules. The placebo is administered at a dosage of 9g, dissolved in boiling water, and taken three times daily.

Interventions

hypoglycemic treatment

The diabetes management adheres to the "The 2025 Guidelines for Standards of Diabetes Care" issued by the American Diabetes Association (ADA).

Intervention Type: DRUG

Tangshen'an Granules

Tangshen'an Granules comprises a meticulously blended mix of Astragalus, Prepared Rehmannia Root, Dodder Seed, Kudzu Root, Millettia Speciosa Champ, Salviae Miltiorrhizae Radix et Rhizoma, Poria Cocos, and Polygala Tenuifolia. Tangshen'an Granules is administered at a dosage of 9g, dissolved in boiling water, and taken three times daily.

Intervention Type: DRUG

Ginkgo Leaf Tablets

The primary active ingredients of Ginkgo Leaf Tablets are ginkgo flavonoid glycosides and terpene lactones. The prescribed oral dosage is one tablet each time, administered three times a day.

Intervention Type: DRUG

Mecobalamin Tablets

Mecobalamin Tablets primarily contain mecobalamin, which is a coenzyme-active form of vitamin B12. The prescribed oral dosage is 0.5mg, administered three times a day.

Intervention Type: DRUG

placebo

The placebo contains 10% of the active ingredients in Tangshen'an Granules, formulated by controlling the concentration to mimic Tangshen'an Granules. The placebo is administered at a dosage of 9g, dissolved in boiling water, and taken three times daily.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Participants who comply with the diagnostic criteria for DM according to the World Health Organization in 1999.

• Participants who fulfill the diagnostic criteria for diabetic NCI.

③ Participants who diagnosed with the syndrome of kidney deficiency and blood stasis according to TCM syndrome differentiation.

④ Participants who have a glycated hemoglobin(HbA1c) level of ≤9%.

⑤ Participants who are aged between 18 and 70 years inclusive, with no gender preference.

⑥Participants who sign informed consent form.

Exclusion Criteria

• Participants exhibiting retinopathy induced by alternative etiological factors (including retinal vein occlusion, age-related macular degeneration(AMD), alongside cognitive impairments stemming from endocrine-metabolic disturbances, sleep disorders.

• Participants suffering from acute diabetic complications (such as diabetic ketoacidosis, hyperosmolar hyperglycemic state).

• Participants with significant dysfunction in the heart, liver, kidney, or autoimmune disorders.

④Participants unable to cooperate due to mental health issues, intellectual disabilities, or similar conditions that impede their participation in the trial.

⑤Participants who are allergic to the intervention used in this study.

⑥Participants who have engaged in other trials within the past three months or are currently enrolled in another study.

⑦Female participants who are in the process of trying to conceive, are pregnant, or are lactating.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hejiang Ye

OTHER

Sponsor Role: lead

Responsible Party

Hejiang Ye

Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Locations

Hospital of Chengdu University of Traditional Chinese Medicine

Chengdu, Sichuan, China

Deyang Hospital Affiliated to Chengdu University of Traditional Chinese Medicine

Deyang, Sichuan, China

Guangyuan North Sichuan Diabetes Specialty Hospital

Guangyuan, Sichuan, China

Countries

China

Central Contacts

Hejiang Ye, Professor

Role: CONTACT

Hejiangye2024@163.com

+86-877867380

Facility Contacts

Dingmeng Zhao, PhD

Role: primary

zhaodingmeng@stu.cdutcm.edu.cn

+86-18482111410

Yunxi Xu, PhD

Role: primary

xuyunxi@stu.cdutcm.edu.cn

+86-15196052194

Chuning Wang, PhD

Role: primary

wangchuning@stu.cdutcm.edu.cn

+86-18482108534

References

Mondal R, Deb S, Chowdhury D, Sarkar S, Guha Roy A, Shome G, Sarkar V, Lahiri D, Benito-Leon J. Neurometabolic substrate transport across brain barriers in diabetes mellitus: Implications for cognitive function and neurovascular health. Neurosci Lett. 2024 Nov 20;843:138028. doi: 10.1016/j.neulet.2024.138028. Epub 2024 Oct 24.

Reference Type: BACKGROUND

PMID: 39461703 (View on PubMed)

Martins B, Pires M, Ambrosio AF, Girao H, Fernandes R. Contribution of extracellular vesicles for the pathogenesis of retinal diseases: shedding light on blood-retinal barrier dysfunction. J Biomed Sci. 2024 May 10;31(1):48. doi: 10.1186/s12929-024-01036-3.

Reference Type: BACKGROUND

PMID: 38730462 (View on PubMed)

American Diabetes Association Professional Practice Committee. 2. Diagnosis and Classification of Diabetes: Standards of Care in Diabetes-2024. Diabetes Care. 2024 Jan 1;47(Suppl 1):S20-S42. doi: 10.2337/dc24-S002.

Reference Type: BACKGROUND

PMID: 38078589 (View on PubMed)

Other Identifiers

2023ZD001

Identifier Type: -

Identifier Source: org_study_id