Multicenter RCT of Eye-Brain Imaging in Diabetes Neurovascular Coupling

Phase 2

Not yet recruiting

• Conditions: Diabetes Mellitus; Diabetic Retinopathy; Cognitive Impairment; Neurovascular Coupling
• Interventions: Drug: hypoglycemic treatment; Drug: Tangshen'an Granules; Drug: Ginkgo Leaf Tablets; Drug: Mecobalamin Tablets; Drug: placebo

• Registration Number: NCT06813274
• Lead Sponsor: Hejiang Ye

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.

Study Timeline

• Status Verified: 2025-01
• Study First Submitted: 2025-01-26
• Study First Submitted QC: 2025-02-03
• Last Update Submitted: 2025-02-03
• Study First Posted: 2025-02-06
• Last Update Posted: 2025-02-06
• Study Start: 2025-05-01
• Primary Completion: 2026-05-01
• Study Completion: 2026-12-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 160

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

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

Primary Outcome Measures

Name	Time	Method
Retinal Nerve Fiber Layer Thickness (RNFL)	From the date of randomization until the end of the 24-week intervention period	The measurement of Retinal Nerve Fiber Layer Thickness (RNFL) is crucial in ophthalmology. Its main parameter is RNFL thickness, which represents the overall average thickness across the entire measured retinal area and is a fundamental metric for initial assessment with a decrease often linked to optic nerve damage.The measurement is often obtained using optical coherence tomography (OCT), a non-invasive imaging technique that delivers high-resolution, cross-sectional images of the retinal layers.
Foveal Avascular Zone (FAZ)	From the date of randomization until the end of the 24-week intervention period	Foveal Avascular Zone (FAZ) is a crucial parameter in retinal imaging, particularly for evaluating macular vascular integrity and diagnosing retinal vascular diseases, such as diabetic retinopathy. The key parameter is the FAZ area, which provides a detailed morphological and functional assessment of the foveal microvasculature. This measurement is commonly obtained using optical coherence tomography angiography (OCTA), which offers high-resolution, depth-resolved visualization of the retinal vasculature without the need for dye injection.
Visual Evoked Potential (VEP)	From the date of randomization until the end of the 24-week intervention period	Visual Evoked Potential (VEP) is a neurophysiological technique used to assess the functional integrity of the visual pathway, from the retina to the visual cortex, by measuring the electrical activity generated in response to visual stimuli. Its main parameter is the latency of the P100 wave, which represents the time delay (in milliseconds) between the presentation of a visual stimulus and the peak of the positive waveform occurring around 100 milliseconds post-stimulus. VEP measurement is typically conducted using an electroencephalogram system equipped with specialized software for stimulus presentation and signal analysis, making it an essential tool for evaluating visual pathway integrity, diagnosing neurological disorders, and monitoring disease progression or treatment efficacy.
Gray matter volume (GMV)	From the date of randomization until the end of the 24-week intervention period	Gray matter volume (GMV) is a pivotal aspect in neuroimaging research, particularly focusing on the structural properties of the brain. A primary parameter in GMV measurement is the absolute volume, which quantifies the volume occupied by neuronal cell bodies, dendrites, and synapses within specific brain regions. This parameter offers crucial insights into brain development, aging, and the pathophysiology of neurological and psychiatric disorders. The GMV is commonly measured by magnetic resonance imaging (MRI) scanners, specifically high-field strength MRI systems that provide superior spatial resolution and contrast.
Montreal Cognitive Assessment（MoCA）score	From the date of randomization until the end of the 24-week intervention period	The Montreal Cognitive Assessment (MoCA) score is a widely used cognitive screening tool designed to detect mild cognitive impairment and early stages of dementia. It assesses multiple cognitive domains, including attention, executive functions, memory, language, visuospatial abilities, abstraction, calculation, and orientation. The MOCA scale will be downloaded from the official website (https://www.mocatest.org).The test consists of 30 items, with a maximum score of 30 points, and typically takes 10-15 minutes to administer. A score of 26 or above is generally considered normal, while scores below 26 may indicate cognitive impairment.The MoCA is administered by a trained clinician or researcher who scores the participant's performance based on standardized criteria, providing a comprehensive assessment of cognitive function.
Mini - Mental State Examination（MMSE）score	From the date of randomization until the end of the 24-week intervention period	The Mini-Mental State Examination (MMSE) score is a widely utilized cognitive screening instrument designed to assess cognitive impairment. It evaluates multiple cognitive domains, including orientation, memory, attention, language, and visuospatial abilities, through a series of questions and tasks. The MMSE will be downloaded from the official website at https://www.parinc.com.The MMSE, administered by a trained investigator, consists of 30 items, with a maximum score of 30 points, and typically takes 5-10 minutes to test. A score of below 24 often indicates cognitive impairment.

Secondary Outcome Measures

Name	Time	Method
Symptom scores in traditional Chinese medicine	From the date of randomization until the end of the 24-week intervention period	Symptom scores in Traditional Chinese Medicine (TCM) are a systematic approach to quantifying and evaluating clinical manifestations based on TCM theory. These scores, administered by a trained investigator, typically assess a range of symptoms, including but not limited to fatigue, pain, digestive issues, sleep disturbances, emotional states, and specific organ-related dysfunctions, through structured questionnaires or clinical observation. The degree can be scored from mild to severe.
Glucose metabolism indicators:Hemoglobin A1c (HbA1c)	From the date of randomization until the end of the 24-week intervention period	Hemoglobin A1c (HbA1c) is a critical biomarker used to assess long-term glycemic control in individuals with diabetes, reflecting the average blood glucose levels over the preceding 2-3 months. The measurement of HbA1c include high-performance liquid chromatography (HPLC), immunoassay, and affinity chromatography, each offering high precision and accuracy.
Glucose metabolism indicators:Fasting blood glucose	From the date of randomization until the end of the 24-week intervention period	Fasting Blood Glucose (FBG) is a fundamental test used to measure blood sugar levels after an individual has fasted for at least 8 hours. It is a key diagnostic tool for assessing glucose metabolism and identifying conditions such as diabetes mellitus, prediabetes, and insulin resistance.The measurement is performed using enzymatic methods, such as glucose oxidase or hexokinase assays, which provide high specificity and accuracy.
Quality of Life Scale (SF-36)	From the date of randomization until the end of the 24-week intervention period	The SF-36 is a widely utilized questionnaire that measures health-related quality of life including physical functioning, bodily pain, general health perceptions, vitality, social functioning and mental health. It employs a standardized set of questions with weighted response options, enabling the quantification of an individual's health status thus serving as a valuable tool in clinical research, healthcare evaluation, and policy-making.

Trial Locations

Locations (3)

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