Cardiovascular Risk, Endothelial Dysfunction, Type 2 Diabetes Mellitus
Conditions
Keywords
Huangqi Gegen Decoction, Qi-Yin Deficiency Syndrome, Flow-Mediated Dilation, Endothelial Function, Traditional Chinese Medicine, Atherosclerotic Cardiovascular Disease, ASCVD
Brief summary
This clinical trial evaluates whether Huangqi Gegen Decoction can improve blood vessel function in adults with type 2 diabetes mellitus who are at very high risk of atherosclerotic cardiovascular disease and meet the traditional Chinese medicine criteria for Qi-Yin deficiency syndrome. A total of 90 participants are randomly assigned in a 1:1 ratio to receive either Huangqi Gegen Decoction granules or matching placebo granules, in addition to their usual guideline-based treatment, for 12 weeks. Participants and investigators are blinded to treatment assignment. The main outcome is flow-mediated dilation (FMD), a noninvasive measure of how well blood vessels dilate. The study also evaluates blood glucose control, blood markers related to endothelial function and inflammation, traditional Chinese medicine syndrome scores, and safety. The investigators hypothesize that Huangqi Gegen Decoction, when added to conventional treatment, will improve endothelial function compared with placebo.
Detailed description
This is a single-center, randomized, double-blind, placebo-controlled clinical trial conducted at Putuo Hospital, Shanghai University of Traditional Chinese Medicine. Eligible participants are adults aged 18 to 75 years with type 2 diabetes mellitus, very high risk of atherosclerotic cardiovascular disease, and Qi-Yin deficiency syndrome according to traditional Chinese medicine criteria. Participants are randomly assigned in a 1:1 ratio to the experimental group or the placebo control group. Both groups continue stable conventional treatment for diabetes and cardiovascular risk management. The experimental group receives Huangqi Gegen Decoction granules in addition to conventional treatment, while the control group receives matching placebo granules in addition to conventional treatment. The intervention period is 12 weeks. The study medication and placebo are designed to have similar appearance, packaging, and administration, and participants and investigators remain blinded to treatment assignment. Participants are assessed at baseline and followed during the 12-week treatment period. Flow-mediated dilation is assessed as the primary measure of endothelial function. Additional assessments include glucose metabolism, biomarkers related to endothelial function and inflammation, traditional Chinese medicine syndrome scores, and safety outcomes. Adverse events and concomitant medications are monitored throughout the study. The study is designed to determine whether adding Huangqi Gegen Decoction to conventional treatment provides additional improvement in endothelial function and related clinical measures compared with conventional treatment plus placebo.
Interventions
DRUGHuangqi Gegen Decoction Granules
Huangqi Gegen Decoction granules consist of Huangqi 30 g and Gegen 15 g per daily prescription. Participants receive 2 bags per administration, twice daily, for 12 weeks, in addition to stable conventional treatment. The granules are manufactured by Jiangyin Tianjiang Pharmaceutical Co., Ltd.
DRUGPlacebo Granules
Matching placebo granules mainly consist of maltodextrin. Participants receive 2 bags per administration, twice daily, for 12 weeks, in addition to stable conventional treatment. The placebo is matched to Huangqi Gegen Decoction granules in appearance, packaging, dosage, and administration.
OTHERConventional Treatment
Participants continue their stable pre-study conventional treatment regimen for diabetes and cardiovascular risk management throughout the 12-week study. Treatment is continued according to the participant's pre-study regimen and relevant Chinese clinical guidelines, with clinically necessary adjustments permitted for safety.
Sponsors
Putuo Hospital, Shanghai University of Traditional Chinese Medicine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Participants and investigators are blinded to treatment assignment. Huangqi Gegen Decoction granules and placebo granules are matched in appearance, packaging, and administration. The data analyst also remains blinded to treatment assignment. Unblinding is permitted at the end of the study or when necessary for participant safety in the event of a serious adverse event.
Intervention model description
Participants are randomized in a 1:1 ratio to two parallel groups receiving Huangqi Gegen Decoction granules or matching placebo granules in addition to conventional treatment for 12 weeks.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Aged 18 to 75 years. * Diagnosed with type 2 diabetes mellitus, with fasting plasma glucose \<9.0 mmol/L and glycated hemoglobin (HbA1c) \<8.5%, and receiving a stable glucose-lowering treatment regimen without adjustment during the previous 3 months. * Type 2 diabetes mellitus with target-organ damage or at least 3 additional cardiovascular risk factors. * Meets the diagnostic criteria for Qi-Yin deficiency syndrome in traditional Chinese medicine, including: (a) primary symptoms of dry mouth and thirst, palpitations, and shortness of breath; (b) secondary symptoms including spontaneous sweating, fatigue, chest tightness, chest discomfort or pain, heat sensation in the palms and soles, polyuria, or constipation; and (c) dark-red tongue and weak, thready pulse. The diagnosis requires at least 2 primary symptoms together with supporting secondary symptoms and tongue/pulse findings, and must be confirmed by at least 2 traditional Chinese medicine physicians at attending-physician level or above. * Voluntarily participates in the study and provides written informed consent. * Has received stable conventional treatment for at least 3 months before enrollment, with the treatment regimen consistent with relevant Chinese clinical guidelines for diabetes and chronic coronary syndromes.
Exclusion criteria
* Allergy to the traditional Chinese medicines used in the study or a history of multiple drug allergies. * History of severe arrhythmia, including recurrent or symptomatic ventricular tachycardia or atrial fibrillation with rapid ventricular response, or New York Heart Association (NYHA) functional class III-IV heart failure. * Abnormal thyroid function, including hyperthyroidism or hypothyroidism, defined as thyroid-stimulating hormone below the lower limit of normal or greater than 1.5 times the upper limit of normal. * History of malignant tumor within the previous 5 years. * Major surgery within the previous 3 months or planned major surgery during the study period. * Long-term or repeated use of systemic glucocorticoids within the previous 3 months. * Active infectious disease at screening or randomization, psychiatric illness, pregnancy or breastfeeding, or any other condition considered by the investigator to make participation inappropriate. * Current use of other medications that may significantly affect systemic immune function. * Acute infection or an active inflammatory condition, such as a respiratory tract infection or recent surgery. * Hematologic disorders that may affect immune or inflammatory markers, including chronic myeloid leukemia, idiopathic thrombocytopenic purpura, or aplastic anemia. * Current use of long-acting nitrates or other medications that may affect vasodilatory function. * Use of other traditional Chinese medicine preparations or dietary supplements with known anti-inflammatory or antioxidant effects, such as curcumin or coenzyme Q10, within 1 month before screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Flow-Mediated Dilation (FMD) | Baseline and Week 12 | Flow-mediated dilation (FMD) is assessed at baseline and after 12 weeks of treatment using the standardized FMD assessment procedure specified in the study protocol. The change from baseline to Week 12 will be compared between the two treatment groups. Higher FMD values indicate better endothelial-dependent vasodilatory function. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Interleukin-18 (IL-18) | Baseline and Week 12 | Interleukin-18 (IL-18) is measured at baseline and Week 12 as an inflammation-related biomarker. The change from baseline will be compared between the two treatment groups. |
| Change From Baseline in Traditional Chinese Medicine Syndrome Score | Baseline and Week 12 | The traditional Chinese medicine syndrome score is assessed according to the prespecified criteria for Qi-Yin deficiency syndrome, including primary symptoms, secondary symptoms, tongue characteristics, and pulse characteristics. The change from baseline to Week 12 will be evaluated. |
| Number of Participants With Adverse Events | From the start of treatment through Week 12 | The number of participants experiencing at least one adverse event during the 12-week treatment period will be recorded. Adverse events are documented regardless of their relationship to the study intervention. |
| Change From Baseline in Thromboxane B2 (TXB2) | Baseline and Week 12 | Thromboxane B2 (TXB2) is measured at baseline and Week 12 using the prespecified laboratory method. The change from baseline will be compared between the two treatment groups. |
| Change From Baseline in Endothelial Nitric Oxide Synthase (eNOS) | Baseline and Week 12 | Endothelial nitric oxide synthase (eNOS) is assessed at baseline and Week 12 as a marker related to endothelial function. The change from baseline will be compared between the two treatment groups. |
| Change From Baseline in Endothelin-1 (ET-1) | Baseline and Week 12 | Endothelin-1 (ET-1), a biomarker associated with vascular endothelial function, is measured at baseline and Week 12. The change from baseline will be compared between groups. |
| Change From Baseline in Fasting Plasma Glucose (FPG) | Baseline and Week 12 | Fasting plasma glucose is measured at baseline and Week 12. The change from baseline to Week 12 will be compared between the two treatment groups. |
| Change From Baseline in 2-Hour Postprandial Blood Glucose | Baseline and Week 12 | Two-hour postprandial blood glucose is measured at baseline and Week 12. The change from baseline to Week 12 will be compared between the two treatment groups. |
| Change From Baseline in Glycated Hemoglobin (HbA1c) | Baseline and Week 12 | Glycated hemoglobin (HbA1c) is measured at baseline and Week 12. The change from baseline to Week 12 will be compared between the two treatment groups. |
| Change From Baseline in Soluble Vascular Cell Adhesion Molecule-1 (sVCAM-1) | Baseline and Week 12 | Soluble vascular cell adhesion molecule-1 (sVCAM-1), a biomarker related to endothelial activation and inflammation, is measured at baseline and Week 12. The change from baseline will be compared between groups. |
| Change From Baseline in von Willebrand Factor (vWF) | Baseline and Week 12 | Von Willebrand factor (vWF), a biomarker related to endothelial function, is measured at baseline and Week 12 using the prespecified laboratory method. The change from baseline will be compared between groups. |
Countries
China
Outcome results
None listed