Traditional Chinese Medicine Intervention for Ischemic Cerebrovascular Disease and Diabetes Mellitus: An Efficacy Comparative Study

NCT ID: NCT07121088

Last Updated: 2025-08-13

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 3666 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-08-31
• Study Completion Date: 2027-12-31

Brief Summary

The objective of this observational study is to understand the long-term effects of traditional Chinese medicine (TCM) intervention on patients with cerebral infarction onset within <48 hours and comorbid diabetes. The primary question it aims to address is:

Can long-term TCM intervention for the treatment of ischemic cerebrovascular disease comorbid with diabetes improve patients' neurological deficits and self-care ability? Participants receiving TCM intervention (universal treatment combined with syndrome-specific treatment) as part of routine cerebrovascular disease management will undergo follow-up assessments at 30 days, 90 days, 6 months, and 12 months within 1 year to evaluate neurological status (e.g., mRS score, NIHSS score) and quality of life indicators.

Detailed Description

The population with ischemic cerebrovascular disease (ICVD) comorbid with diabetes is growing, characterized by high mortality, disability, and recurrence rates of vascular events, with a lack of effective treatments. There are 529 million diabetic patients worldwide and 129 million in China, among which 43 million have comorbid vascular diseases; China has approximately 10 million ischemic stroke patients, with 4.5 million comorbid diabetes. Diabetes increases the risk of ischemic stroke, and the proportion of deaths related to diabetic cerebrovascular diseases has risen significantly. Polypharmacy also raises the risk of adverse drug interactions, imposing a heavy medical burden.

The pathological mechanism aligns with the TCM theory of "toxin damaging collaterals": Diabetes-induced glucose/lipid metabolism disorders and activation of the renin-angiotensin-aldosterone system cause systemic vascular endothelial dysfunction and atherosclerosis. Macrovascular lesions mainly involve atherosclerosis, while microvascular lesions include endothelial damage and microcirculatory disorders, with core mechanisms involving energy metabolism abnormalities and mitochondrial dysfunction. TCM holds that "excessive pathogens transform into toxins," and toxin-induced collateral damage disrupts structure and function, consistent with the above pathology. Thus, "detoxification and collaterals dredging" (combining qi-nourishing, blood-activating, and stasis-removing) is the core therapeutic principle.

Chuanzhi Tongluo Capsules (Lunan Pharmaceutical), a Shandong famous brand with annual sales over 100 million yuan, exert effects of promoting blood circulation and dredging collaterals, reducing inflammation and improving microcirculation. This project explores a TCM program combining "acute-phase intensive treatment + recovery-phase sequential treatment" and "universal + syndrome-specific treatment." Entitled Comparative Efficacy Study of TCM Intervention in ICVD Comorbid with Diabetes, this Phase IV trial spans 4 years, adopting a multi-center real-world non-randomized controlled design. It will enroll 3,666 patients with acute cerebral infarction (onset <48h) comorbid diabetes across 50 centers. The control group receives standard secondary prevention of cerebrovascular disease and hypoglycemic treatment; the trial group adds Chuanzhi Tongluo Capsules (4 capsules thrice daily for 14 days, then 2 capsules thrice daily for 1 year) plus syndrome-specific treatment (5 TCM syndromes with corresponding herbs for 14 days).

Inclusion criteria: ≥18 years old, meeting diabetes/acute ischemic stroke criteria, and TCM "toxin damaging brain collaterals" syndrome. Exclusions: hemorrhagic transformation, large infarction, type 1 diabetes, etc. The primary endpoint is the proportion of patients with mRS 0-2 at 90 days. Secondary endpoints include 1-year BARC type III/V major bleeding, MACCE, all-cause mortality, diabetic microvascular lesions (renal indices), mRS, MMSE, and EQ-5D-5L at 6/12 months. Data are managed via EpiData and analyzed with SAS, using chi-square test, t-test, and rank sum test, with 90% statistical power (α=0.05, β=0.10). The trial aims to establish a "disease-syndrome combined" long-term intervention model, expanding TCM applicability and evidence generalization.

English Abbreviation The population with ischemic cerebrovascular disease (ICVD) comorbid with diabetes is growing, with high mortality, disability, and recurrence rates of vascular events, and a lack of effective treatments. Globally, there are 529 million diabetic patients, including 129 million in China, among whom 43 million have comorbid vascular diseases; China has ~10 million ischemic stroke patients, with ~4.5 million comorbid diabetes. Diabetes elevates ischemic stroke risk, and related deaths are increasing, while polypharmacy raises adverse interactions and medical burdens.

Pathologically, it aligns with TCM's "toxin damaging collaterals" theory: Diabetes-induced metabolic disorders and systemic vascular activation cause endothelial dysfunction and atherosclerosis (macrovascular lesions) and microcirculatory disorders (microvascular lesions), involving energy metabolism and mitochondrial dysfunction. TCM holds toxins damage collaterals, disrupting structure/function, consistent with the pathology, so "detoxification and collaterals dredging" (combining qi-nourishing, blood-activating) is key.

Chuanzhi Tongluo Capsules (Lunan Pharmaceutical), a Shandong famous brand with annual sales over ¥100 million, improve circulation and reduce inflammation. This Phase IV trial (4 years) uses a multi-center real-world non-randomized design, enrolling 3,666 patients (onset <48h) across 50 centers. The control group receives standard care; the trial group adds Chuanzhi Tongluo Capsules (intensive: 4 caps thrice daily for 14 days; sequential: 2 caps thrice daily for 1 year) plus syndrome-specific herbs for 5 TCM syndromes.

Inclusion: ≥18 years, meeting diabetes/ischemic stroke criteria, and "toxin damaging brain collaterals" syndrome. Exclusions: hemorrhagic transformation, large infarction, type 1 diabetes, etc. Primary endpoint: 90-day mRS 0-2 proportion. Secondary endpoints: 1-year BARC III/V bleeding, MACCE, mortality, diabetic microvascular lesions, mRS, MMSE, EQ-5D-5L at 6/12 months. Analyzed via EpiData and SAS (chi-square, t-test, rank sum test) with 90% power (α=0.05, β=0.10). It aims to establish a "disease-syndrome combined" model, expanding TCM applicability and evidence generalization.

Conditions

Ischemic Cerebral Infarction; Diabetes Mellitus

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Chuanzhitongluo capsule+Standard Treatment

On the basis of standard treatment, a combined treatment plan of TCM universal treatment and syndrome-specific treatment was given.

TCM universal treatment plan:

(Intensive treatment) Chuanzhi Tongluo Capsules (Lunan Pharmaceutical), 4 capsules each time, orally, 3 times a day; administration from day 1 to day 14 of the disease.

(Sequential treatment) Chuanzhi Tongluo Capsules (Lunan Pharmaceutical), 2 capsules each time, orally, 3 times a day; administration from day 15 to day 365.

TCM decoction: Individualized herbal decoction based on TCM diagnosis (four diagnostic methods), administered for 14 days during intensive phase.

Group Type: EXPERIMENTAL

(Intensive treatment) Chuanzhi Tongluo Capsules

Intervention Type: DRUG

4 capsules each time, orally, 3 times a day; administration from day 1 to day 14 of the disease.

(Sequential treatment) Chuanzhi Tongluo Capsules

Intervention Type: DRUG

2 capsules each time, orally, 3 times a day; administration from day 15 to day 365.

TCM Syndrome Differentiation Decoction

Intervention Type: DRUG

Individualized herbal decoction based on TCM diagnosis (four diagnostic methods), administered for 14 days during intensive phase.

Standard Treatment Only

Guideline-based treatment for cerebral infarction with diabetes: aspirin (100 mg/day) + clopidogrel (75 mg/day) + atorvastatin (20 mg/day) + metformin (500 mg bid). Other antiplatelet/antidiabetic drugs may be added per clinician discretion.

Group Type: ACTIVE_COMPARATOR

Standard Treatment (Guideline-Based)

Intervention Type: OTHER

Combination therapy including: 1. Antiplatelet: aspirin 100 mg/day + clopidogrel 75 mg/day. 2. Lipid-lowering: atorvastatin 20 mg/day. 3. Antidiabetic: metformin 500 mg bid (max 2000 mg/day). \*Doses may be adjusted per local guidelines or patient tolerance.

Interventions

(Intensive treatment) Chuanzhi Tongluo Capsules

4 capsules each time, orally, 3 times a day; administration from day 1 to day 14 of the disease.

Intervention Type: DRUG

Standard Treatment (Guideline-Based)

Combination therapy including: 1. Antiplatelet: aspirin 100 mg/day + clopidogrel 75 mg/day. 2. Lipid-lowering: atorvastatin 20 mg/day. 3. Antidiabetic: metformin 500 mg bid (max 2000 mg/day). \*Doses may be adjusted per local guidelines or patient tolerance.

Intervention Type: OTHER

(Sequential treatment) Chuanzhi Tongluo Capsules

2 capsules each time, orally, 3 times a day; administration from day 15 to day 365.

Intervention Type: DRUG

TCM Syndrome Differentiation Decoction

Individualized herbal decoction based on TCM diagnosis (four diagnostic methods), administered for 14 days during intensive phase.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Age ≥ 18 years old, regardless of gender.

2. Previously diagnosed with diabetes, or with an unknown medical history, meeting the WHO 2023 diagnostic criteria for type 2 diabetes, including any of the following:

• Fasting blood glucose ≥ 7.0 mmol/L.
• 2-hour postprandial blood glucose ≥ 11.1 mmol/L.
• Glycated hemoglobin ≥ 6.5%.

3. Acute cerebral infarction meets the diagnostic criteria of *Chinese Guidelines for the Diagnosis and Treatment of Acute Ischemic Stroke 2023*:

• Acute onset.
• Focal neurological deficits, with a few cases showing global neurological deficits.
• The presence of a responsible lesion on imaging or symptoms/signs persisting for more than 24 hours.
• Exclusion of non-vascular etiologies.
• Exclusion of intracerebral hemorrhage by brain CT/MRI.

4. Onset of cerebral infarction < 48 hours.

5. TCM syndrome conforms to the "toxin damaging brain collaterals" syndrome (referring to the diagnostic criteria (draft) of *Research on the Diagnostic Criteria for the Syndrome of Mutual Binding of Stasis and Toxin in Ischemic Cardiovascular and Cerebrovascular Diseases* (Ju Jianqing et al., 2023)).

6. Modified Rankin Scale (mRS) before onset: 0 - 1 point.

7. National Institutes of Health Stroke Scale (NIHSS) at admission: 4 - 24 points.

8. Signed informed consent form.

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

Sponsors

Guangzhou University of Traditional Chinese Medicine

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Central Contacts

Tao Huang, doctor

Role: CONTACT

arteries@163.com

18688898958

zheng zhen, master

Role: CONTACT

devotetcm@163.com

19120517600

Other Identifiers

2023ZD0505604

Identifier Type: -

Identifier Source: org_study_id