Clinical trial NCT06813274: Multicenter RCT of Eye-Brain Imaging in Diabetes Neurovascular Coupling
Official title: Multicenter, Double Blind, Randomized, Placebo-controlled Trial to Exploring the Role of Eye-Brain Multimodal Imaging in Diagnosing and Treating Neurovascular Coupling Impairment in Diabetes Mellitus
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
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
Lead sponsor: Chengdu University of Traditional Chinese Medicine
Sponsor class: OTHER
First posted: 2025-02-06
Enrollment: 160
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This study adopts a block randomization technique to allocate participants into groups, maintaining a 1:1 ratio between the experimental and control arms.
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Retinal Nerve Fiber Layer Thickness (RNFL)
timeFrame: From the date of randomization until the end of the 24-week intervention period
measure: Foveal Avascular Zone (FAZ)
timeFrame: From the date of randomization until the end of the 24-week intervention period
measure: Visual Evoked Potential (VEP)
timeFrame: From the date of randomization until the end of the 24-week intervention period
measure: Gray matter volume (GMV)
timeFrame: From the date of randomization until the end of the 24-week intervention period
measure: Montreal Cognitive Assessment（MoCA）score
timeFrame: From the date of randomization until the end of the 24-week intervention period
measure: Mini - Mental State Examination（MMSE）score
timeFrame: From the date of randomization until the end of the 24-week intervention period
Secondary outcomes:
measure: Symptom scores in traditional Chinese medicine
timeFrame: From the date of randomization until the end of the 24-week intervention period
measure: Glucose metabolism indicators:Hemoglobin A1c (HbA1c)
timeFrame: From the date of randomization until the end of the 24-week intervention period
measure: Glucose metabolism indicators:Fasting blood glucose
timeFrame: From the date of randomization until the end of the 24-week intervention period
measure: Quality of Life Scale (SF-36)
timeFrame: From the date of randomization until the end of the 24-week intervention period
Other outcomes:
measure: Blood Routine Test：White Blood Cell Count (WBC)
timeFrame: From the date of randomization until the end of the 24-week intervention period
measure: Blood Routine Test: Red Blood Cell Count (RBC)
timeFrame: From the date of randomization until the end of the 24-week intervention period
measure: Blood Routine Test:Hemoglobin
timeFrame: From the date of randomization until the end of the 24-week intervention period
measure: Blood Routine Test:Packed Cell Volume
timeFrame: From the date of randomization until the end of the 24-week intervention period
measure: Blood Routine Test:Platelet Count
timeFrame: From the date of randomization until the end of the 24-week intervention period
measure: Blood Routine Test:Neutrophil Count
timeFrame: From the date of randomization until the end of the 24-week intervention period
measure: Blood Routine Test:Lymphocyte Count
timeFrame: From the date of randomization until the end of the 24-week intervention period
measure: Urine Routine Test:Urine pH
timeFrame: From the date of randomization until the end of the 24-week intervention period
measure: Urine Routine Test:Urine Protein
timeFrame: From the date of randomization until the end of the 24-week intervention period
measure: Urine Routine Test:Occult Blood
timeFrame: From the date of randomization until the end of the 24-week intervention period
measure: Urine Routine Test:Red Blood Cells
timeFrame: From the date of randomization until the end of the 24-week intervention period
measure: Urine Routine Test:White Blood Cells
timeFrame: From the date of randomization until the end of the 24-week intervention period
measure: Urine Routine Test:Urine ketones
timeFrame: From the date of randomization until the end of the 24-week intervention period
measure: Renal Function Tests：Creatinine
timeFrame: From the date of randomization until the end of the 24-week intervention period
measure: Renal Function Tests：Estimated Glomerular Filtration Rate (eGFR)
timeFrame: From the date of randomization until the end of the 24-week intervention period
measure: Hepatic Function Tests：Aspartate Aminotransferase (AST)
timeFrame: From the date of randomization until the end of the 24-week intervention period
measure: Hepatic Function Tests：Alanine Aminotransferase (ALT)
timeFrame: From the date of randomization until the end of the 24-week intervention period
measure: Hepatic Function Tests：Glutamyl Transferase (GGT)
timeFrame: From the date of randomization until the end of the 24-week intervention period
measure: QT interval on 18-lead electrocardiogram（ECG）
timeFrame: From the date of randomization until the end of the 24-week intervention period
Locations:
city: Chengdu
country: China
facility: Hospital of Chengdu University of Traditional Chinese Medicine
state: Sichuan
city: Deyang
country: China
facility: Deyang Hospital Affiliated to Chengdu University of Traditional Chinese Medicine
state: Sichuan
city: Guangyuan
country: China
facility: Guangyuan North Sichuan Diabetes Specialty Hospital
state: Sichuan
Study officials:
References:
citation: 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.
citation: 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.
citation: 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.