Multicenter RCT of Eye-Brain Imaging in Diabetes Neurovascular Coupling

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

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

Первичные конечные точки

• Retinal Nerve Fiber Layer Thickness (RNFL) [Срок оценки: From the date of randomization until the end of the 24-week intervention period]
• Foveal Avascular Zone (FAZ) [Срок оценки: From the date of randomization until the end of the 24-week intervention period]
• Visual Evoked Potential (VEP) [Срок оценки: From the date of randomization until the end of the 24-week intervention period]
• Gray matter volume (GMV) [Срок оценки: From the date of randomization until the end of the 24-week intervention period]
• Montreal Cognitive Assessment（MoCA）score [Срок оценки: From the date of randomization until the end of the 24-week intervention period]
• Mini - Mental State Examination（MMSE）score [Срок оценки: From the date of randomization until the end of the 24-week intervention period]

Вторичные конечные точки (4)

• Symptom scores in traditional Chinese medicine [Срок оценки: From the date of randomization until the end of the 24-week intervention period]
• Glucose metabolism indicators:Hemoglobin A1c (HbA1c) [Срок оценки: From the date of randomization until the end of the 24-week intervention period]
• Glucose metabolism indicators:Fasting blood glucose [Срок оценки: From the date of randomization until the end of the 24-week intervention period]
• Quality of Life Scale (SF-36) [Срок оценки: From the date of randomization until the end of the 24-week intervention period]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Двойное слепое

Основная цель

Лечение

Центры проведения

Китай · 3 центра

• Hospital of Chengdu University of Traditional Chinese Medicine — Чэнду
• Deyang Hospital Affiliated to Chengdu University of Traditional Chinese Medicine — Deyang
• Guangyuan North Sichuan Diabetes Specialty Hospital — Guangyuan

Публикации

• 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
• 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
• 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

Идентификаторы

NCT: NCT06813274 · 2023ZD001

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗