Multicenter RCT of Eye-Brain Imaging in Diabetes Neurovascular Coupling

NCT06813274 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: 2023ZD001
• Study Type: interventional
• Target: 160
• Locations: 1 country
• Sites: 3

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.

Conditions

Diabetes Mellitus; Diabetic Retinopathy; Cognitive Impairment; Neurovascular Coupling

Keywords

Eye-Brain Multimodal Imaging; Neurovascular Coupling Impairment; Diabetes Mellitus; Diabetic retinopathy; Diabetic Cognitive Impairment; Traditional Chinese Medicine

Outcome Measures

Primary Outcomes (6)

• Retinal Nerve Fiber Layer Thickness (RNFL)

  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.

  From the date of randomization until the end of the 24-week intervention period

• Foveal Avascular Zone (FAZ)

  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.

  From the date of randomization until the end of the 24-week intervention period

• Visual Evoked Potential (VEP)

  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.

  From the date of randomization until the end of the 24-week intervention period

• Gray matter volume (GMV)

  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.

  From the date of randomization until the end of the 24-week intervention period

• Montreal Cognitive Assessment（MoCA）score

  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.

  From the date of randomization until the end of the 24-week intervention period

• Mini - Mental State Examination（MMSE）score

  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.

  From the date of randomization until the end of the 24-week intervention period

Secondary Outcomes (4)

• Symptom scores in traditional Chinese medicine

  From the date of randomization until the end of the 24-week intervention period

• Glucose metabolism indicators:Hemoglobin A1c (HbA1c)

  From the date of randomization until the end of the 24-week intervention period

• Glucose metabolism indicators:Fasting blood glucose

  From the date of randomization until the end of the 24-week intervention period

• Quality of Life Scale (SF-36)

  From the date of randomization until the end of the 24-week intervention period

Other Outcomes (19)

• Blood Routine Test：White Blood Cell Count (WBC)

  From the date of randomization until the end of the 24-week intervention period

• Blood Routine Test: Red Blood Cell Count (RBC)

  From the date of randomization until the end of the 24-week intervention period

• Blood Routine Test:Hemoglobin

  From the date of randomization until the end of the 24-week intervention period

Study Arms (2)

Intervention Group

EXPERIMENTAL

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

Drug: hypoglycemic treatment; Drug: Tangshen'an Granules; Drug: Ginkgo Leaf Tablets; Drug: Mecobalamin Tablets

Control Group

PLACEBO COMPARATOR

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

Drug: hypoglycemic treatment; Drug: Ginkgo Leaf Tablets; Drug: Mecobalamin Tablets; Drug: placebo

Interventions

hypoglycemic treatment DRUG

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

Control Group; Intervention Group

Tangshen'an Granules 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.

Intervention Group

Ginkgo Leaf Tablets 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.

Control Group; Intervention Group

Mecobalamin Tablets 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; Intervention Group

placebo 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.

Control Group

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Hejiang Ye: lead

Study Sites (3)

Hospital of Chengdu University of Traditional Chinese Medicine

Chengdu, Sichuan, 610072, China

Location

Deyang Hospital Affiliated to Chengdu University of Traditional Chinese Medicine

Deyang, Sichuan, 618000, China

Location

Guangyuan North Sichuan Diabetes Specialty Hospital

Guangyuan, Sichuan, 628000, China

Location

Related Publications (3)

• 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.

  PMID: 39461703 BACKGROUND

• 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.

  PMID: 38730462 BACKGROUND

• 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.

  PMID: 38078589 BACKGROUND

MeSH Terms

Conditions

Diabetes Mellitus; Diabetic Retinopathy; Cognitive Dysfunction

Interventions

mecobalamin

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Retinal Diseases; Eye Diseases; Diabetic Angiopathies; Vascular Diseases; Cardiovascular Diseases; Diabetes Complications; Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Central Study Contacts

Hejiang Ye, Professor

CONTACT

+86-877867380; Hejiangye2024@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: The randomization sequence is crafted by statistical experts uninvolved in the trial's execution, utilizing SAS9.4 software with a predefined seed and an appropriately chosen block length. To ensure consistency, a third-party manufacturer is contracted to produce both the experimental drug and placebo, adhering to uniform labeling and packaging standards. Subsequently, a pharmacist independent of the trial's operational team blinds the medications in accordance with the established randomization sequence. The investigators dispense the drugs sequentially, adhering to the assigned drug numbers and the chronological order of patient enrollment.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Model Details: This study adopts a block randomization technique to allocate participants into groups, maintaining a 1:1 ratio between the experimental and control arms.

Study Record Dates

• First Submitted: January 26, 2025
• First Posted: February 6, 2025
• Study Start: January 1, 2026
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: September 26, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, CSR
• Time Frame: Beginning 1 year after publication and ending 2 years after the publication of results
• Access Criteria: The data that support the findings of this study are available from the corresponding author upon reasonable request.

Locations

CN (3)