Clinical trial NCT06964620: Efficacy and Safety of Sanggua Tablets in the Treatment of Patients With Impaired Glucose Tolerance and Mild Type 2 Diabetes
Official title: Efficacy and Safety of Sanggua Tablets in the Treatment of Patients With Impaired Glucose Tolerance and Mild Type 2 Diabetes
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: EARLY_PHASE1
Conditions: Diabetes Mellitus, Type 2
Impaired Glucose Tolerance
Lead sponsor: Tongji Hospital
Sponsor class: OTHER
First posted: 2025-05-09
Enrollment: 84
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Type 2 diabetes mellitus (T2DM) and impaired glucose tolerance (IGT) are growing public health challenges. Early intervention in mild T2DM and IGT is essential to prevent disease progression and severe complications. Traditional Chinese Medicine (TCM) provides a potential therapeutic approach.

Sanggua tablets, a TCM formula composed of mulberry leaf, bitter melon, kudzu root, Chinese yam, and cassia seed, embody TCM principles of clearing heat, generating body fluids, tonifying the spleen and stomach, and nourishing the lungs and kidneys. Modern studies show that Sanggua tablets effectively lower blood glucose and improve lipid profiles through components like mulberry polysaccharides and bitter melon saponins. These findings suggest their potential as an alternative or complementary therapy for mild T2DM and IGT.

This study will conduct a randomized, double-blind, placebo-controlled, parallel-group clinical trial among patients with IGT and mild T2DM. Participants will receive a 16-week intervention with Sanggua tablets. The primary outcome is glycated hemoglobin (HbA1c), with secondary outcomes such as fasting blood glucose (FBG), fasting insulin (FINS), HOMA-IR, lipid profiles and so on. Safety will be closely monitored. Additionally, fecal samples will be collected for 16S rDNA sequencing to explore the role of gut microbiota in the therapeutic effects of Sanggua tablets. This study aims to provide evidence for the clinical application and development of Sanggua tablets as a novel TCM therapy.

Detailed description: Type 2 diabetes mellitus (T2DM) and impaired glucose tolerance (IGT) are significant public health concerns, with rising prevalence rates globally. Treating mild T2DM and IGT is crucial to prevent disease progression and reduce the risk of severe complications such as cardiovascular diseases. Traditional Chinese Medicine (TCM) offers a promising approach in this context.

Sanggua tablets, a TCM formula, consist of mulberry leaf, bitter melon, kudzu root, Chinese yam, and cassia seed. These ingredients work synergistically to achieve the TCM therapeutic principles of clearing heat and detoxifying, generating body fluids and moistening dryness, tonifying the spleen and stomach, and nourishing the lungs and kidneys. Modern pharmacological studies have shown that Sanggua tablets have significant therapeutic potential. Their components, such as mulberry polysaccharides and bitter melon saponins, have been proven to lower blood glucose levels by promoting glycogen synthesis and inhibiting glucose absorption. Additionally, they have demonstrated hypolipidemic effects, improving lipid profiles and potentially preventing atherosclerosis.

Clinical and experimental evidence suggests that Sanggua tablets can effectively improve insulin resistance and regulate lipid metabolism. These findings highlight their potential as an alternative or complementary therapy for mild T2DM and IGT. Further research is needed to elucidate their mechanisms of action and optimize their clinical application.

This study proposes to employ a randomized, double-blind, placebo-controlled, parallel-group clinical trial design. The study population will consist of patients with IGT and mild T2DM. Participants will undergo a 16-week intervention with Sanggua tablets. The primary outcome is glycated hemoglobin (HbA1c), with secondary outcomes such as fasting blood glucose (FBG), fasting insulin (FINS), HOMA-IR, lipid profiles and so on. Safety indicators will also be closely monitored. The clinical efficacy of Sanggua tablets will be re-evaluated through these measures. Additionally, to explore its mechanism of action, fecal samples will be collected from participants for 16S rDNA sequencing to investigate the role of gut microbiota. This study aims to provide evidence for the clinical application and potential development of Sang Gua tablets as a Category 1.1 innovative traditional Chinese medicine.

Based on calculations using the PASS 15 software, a total of 84 participants are required for enrollment, with 42 participants in each group.

Initially screened participants will undergo baseline assessments during the screening period (V0, from Day -7 to Day 0) to determine their eligibility based on the inclusion and exclusion criteria. Randomization of eligible participants and the preparation of randomization envelopes will follow the principles of randomized clinical trial design. Participants meeting the inclusion and exclusion criteria will be randomly assigned to two groups in a 1:1 ratio, receiving either conventional treatment plus Sanggua tablets or conventional treatment plus placebo. Both Sanggua tablets and the placebo will be manufactured by Wuhan Jianmin Dapeng Pharmaceutical Co., Ltd. Random numbers generated using SAS software will be used to determine the codes for participants in the two groups. Two copies of the randomization envelopes will be prepared, sealed, and separately stored by the investigator and the person in charge of the clinical study. After 16 weeks of treatment, the efficacy and safety of the interventions will be evaluated.

Study Visits:

V0 (Screening): Conducted 7 days before enrollment, includes assessments such as physical examination, vital signs, fasting blood glucose (FBG), glycated hemoglobin (HbA1c).

V1 (Enrollment): Occurs on Day 0, where participants are assigned to groups and begin treatment.

V2 (4 weeks): Participants are assessed for FBG, vital signs, and other routine checks.

V3 (8 weeks): Participants are assessed for FBG, vital signs, and additional assessments.

V4 (12 weeks): Participants are assessed for FBG and vital signs assessment. V5 (16 weeks): Final assessment includes physical examination, vital signs, FBG, HbA1c, oral glucose tolerance test (OGTT), and other glycemic and lipid profiles.

V6 (Post-study): Follow-up 28 days after the last dose, includes a telephone interview for any adverse events.

Eligibility criteria: Inclusion Criteria:

* Patients aged 18-70 with impaired glucose tolerance (IGT).
* Patients aged 18-70 diagnosed with type 2 diabetes mellitus (T2DM) deemed by the clinician not requiring pharmacological intervention.
* Glycated hemoglobin (HbA1c) levels between 5.6% and 7.5%.
* Voluntarily sign an informed consent form before the commencement of trial-related activities, understand the procedures and methods of the trial, and are willing and able to strictly adhere to the clinical trial protocol to complete the study.

Exclusion Criteria:

* Type 1 diabetes mellitus.
* Known allergies to Sang Gua tablets or any of its components.
* Use of hypoglycemic or lipid-lowering drugs within the last three months.
* Presence of severe primary or secondary respiratory, cardiovascular, hepatic, or renal diseases, rheumatic connective tissue diseases, or hematological disorders.
* Uncontrolled or unstable conditions exacerbated by infections, severe electrolyte imbalances, or other factors.
* Patients with primary or secondary kidney diseases, hypertension, heart failure, acidosis, or urinary tract infections causing increased urinary protein, excepted.
* Patients with psychiatric disorders.
* Pregnant or planning to become pregnant women, or nursing mothers.
* Patients requiring long-term steroid therapy.
* Patients with poorly controlled hypertension or secondary hypertension.
* Patients who have participated in other clinical trials within the past three months.
* Patients deemed by the investigator as unsuitable for this clinical trial due to potential interference with trial results, impediments to full participation in the study, medical history, disease evidence, abnormal treatments, or laboratory values, or any other condition considered by the investigator to pose potential risks for participation in the study.

Primary outcomes:
measure: Hemoglobin A1c (HbA1c, %)
timeFrame: The percentage of glycated hemoglobin will be measured at baseline (V1) and at the end of the treatment period(Week 16 ,V5).
Secondary outcomes:
measure: Fasting blood glucose (FBG, mmol/L)
timeFrame: FBG will be measured at the following time points during the clinical trial: enrollment visit (V1), Week 4 (V2), Week 8 (V3), Week 12 (V4), and Week 16 (V5).
measure: 2 hour blood glucose (mmol/L)
timeFrame: FBG will be measured at the following time points during the clinical trial: enrollment visit (V1), Week 4 (V2), Week 8 (V3), Week 12 (V4), and Week 16 (V5).
measure: Fasting insulin (FINS, uIU/ml)
timeFrame: FINS will be measured at baseline (V1) and at the end of the treatment period(Week 16 ,V5).
measure: 2 hour insulin (uIU/ml)
timeFrame: FINS will be measured at baseline (V1) and at the end of the treatment period(Week 16 ,V5).
measure: Fasting C-peptide(ug/L)
timeFrame: C-peptide will be measured at baseline (V1) and at the end of the treatment period(Week 16 ,V5).
measure: 2 hour C-peptide(ug/L)
timeFrame: C-peptide will be measured at baseline (V1) and at the end of the treatment period(Week 16 ,V5).
measure: Homeostasis model assessment of insulin resistance (HOMA-IR)
timeFrame: HOMA-IR will be calculated at baseline (V1) and at the end of the treatment period(Week 16 ,V5).
measure: HOMA-β
timeFrame: HOMA-β will be calculated at baseline (V1) and at the end of the treatment period(Week 16 ,V5).
measure: TAR (Time Above Range > 13.9 mmol/L)
timeFrame: Participants will wear CGM devices for two weeks starting one week prior to enrollment, and again for two weeks at the end of the treatment period, beginning one week before the final medication administration.
measure: TAR (Time Above Range 10.1-13.9 mmol/L)
timeFrame: Participants will wear CGM devices for two weeks starting one week prior to enrollment, and again for two weeks at the end of the treatment period, beginning one week before the final medication administration.
measure: TIR (Time in Range 3.9-10.0 mmol/L)
timeFrame: Participants will wear CGM devices for two weeks starting one week prior to enrollment, and again for two weeks at the end of the treatment period, beginning one week before the final medication administration.
measure: TBR (Time Below Range 3.0-3.8 mmol/L)
timeFrame: Participants will wear CGM devices for two weeks starting one week prior to enrollment, and again for two weeks at the end of the treatment period, beginning one week before the final medication administration.
measure: TBR (Time Below Range <3.0 mmol/L)
timeFrame: Participants will wear CGM devices for two weeks starting one week prior to enrollment, and again for two weeks at the end of the treatment period, beginning one week before the final medication administration.
measure: Coefficient of variation
timeFrame: Participants will wear CGM devices for two weeks starting one week prior to enrollment, and again for two weeks at the end of the treatment period, beginning one week before the final medication administration.
measure: Mean sensor glucose
timeFrame: Participants will wear CGM devices for two weeks starting one week prior to enrollment, and again for two weeks at the end of the treatment period, beginning one week before the final medication administration.
measure: Glucose Management Index (GMI)
timeFrame: Participants will wear CGM devices for two weeks starting one week prior to enrollment, and again for two weeks at the end of the treatment period, beginning one week before the final medication administration.
measure: Total Cholesterol（TC,mmol/L）
timeFrame: TC will be measured at baseline (V1) and at the end of the treatment period(Week 16 ,V5).
measure: Triglycerides（TG, mmol/L）
timeFrame: TG will be measured at baseline (V1) and at the end of the treatment period(Week 16 ,V5).
measure: Low-density lipoprotein cholesterol（LDL-C, mmol/L）
timeFrame: LDL-C will be measured at baseline (V1) and at the end of the treatment period(Week 16 ,V5).
measure: High-density lipoprotein cholesterol（HDL-C, mmol/L）
timeFrame: HDL-C will be measured at baseline (V1) and at the end of the treatment period(Week 16 ,V5).
measure: Lipoprotein(a)（Lp(a), mg/L）
timeFrame: LP(a) will be measured at baseline (V1) and at the end of the treatment period(Week 16 ,V5).
measure: Liver Stiffness Measurement(LSM, kPa)
timeFrame: Liver Stiffness Measurement will be measured at baseline (V1) and at the end of the treatment period(Week 16 ,V5).
measure: Controlled attenuation parameter(CAP, dB/m)
timeFrame: Controlled attenuation parameter will be measured at baseline (V1) and at the end of the treatment period(Week 16 ,V5).
measure: C-reactive protein (CRP, mg/L)
timeFrame: CRP will be measured at baseline (V1) and at the end of the treatment period(Week 16 ,V5).
measure: Homocysteine(umol/L)
timeFrame: Homocysteine will be measured at baseline (V1) and at the end of the treatment period(Week 16 ,V5).
measure: Waist circumference(cm)
timeFrame: Waist circumference will be measured at baseline (V1) and at the end of the treatment period(Week 16 ,V5).
measure: Hip circumference(cm)
timeFrame: Waist circumference will be measured at baseline (V1) and at the end of the treatment period(Week 16 ,V5).
measure: Waist-to-hip ratio
timeFrame: Waist-to-hip ratio will be measured at baseline (V1) and at the end of the treatment period(Week 16 ,V5).
measure: Waist-to-height ratio
timeFrame: Waist-to-height ratio will be measured at baseline (V1) and at the end of the treatment period(Week 16 ,V5).
measure: Visceral Fat Area (VFA, cm²)
timeFrame: Visceral Fat Area will be measured at baseline (V1) and at the end of the treatment period(Week 16 ,V5).
measure: Fecal samples for 16S rDNA sequencing
timeFrame: Fecal samples will be collected at baseline (V1) and at the end of the treatment period(Week 16 ,V5) for 16S rDNA sequencing.
measure: Body weight(kg)
timeFrame: Body weight will be measured at baseline (V1) and at the end of the treatment period(Week 16 ,V5).
measure: Body mass index (BMI)
timeFrame: BMI will be measured at baseline (V1) and at the end of the treatment period(Week 16 ,V5).
measure: Heart rate(time/min)
timeFrame: Heart rate will be measured at the following time points during the clinical trial: enrollment visit (V1), Week 4 (V2), Week 8 (V3), Week 12 (V4), and Week 16 (V5).
measure: Systolic Blood Pressure(mmHg)
timeFrame: Systolic blood pressure will be measured at the following time points during the clinical trial: enrollment visit (V1), Week 4 (V2), Week 8 (V3), Week 12 (V4), and Week 16 (V5).
measure: Diastolic Blood Pressure (mmHg)
timeFrame: Diastolic Blood Pressure will be measured at the following time points during the clinical trial: enrollment visit (V1), Week 4 (V2), Week 8 (V3), Week 12 (V4), and Week 16 (V5).
measure: AST(U/L)
timeFrame: AST will be measured at the following time points during the clinical trial: enrollment visit (V1), Week 4 (V2), and Week 16 (V5).
measure: ALT(U/L)
timeFrame: ALT will be measured at the following time points during the clinical trial: enrollment visit (V1), Week 4 (V2), and Week 16 (V5).
measure: Urea(mmol/L)
timeFrame: Urea will be measured at the following time points during the clinical trial: enrollment visit (V1), Week 4 (V2), and Week 16 (V5).
measure: Blood uric acid(umol/L)
timeFrame: Blood uric acid will be measured at the following time points during the clinical trial: enrollment visit (V1), Week 4 (V2), and Week 16 (V5).
measure: Creatinine(umol/L)
timeFrame: Creatinine will be measured at the following time points during the clinical trial: enrollment visit (V1), Week 4 (V2), and Week 16 (V5).
measure: Bicarbonate(mM)
timeFrame: Bicarbonate will be measured at the following time points during the clinical trial: enrollment visit (V1), Week 4 (V2), and Week 16 (V5).
measure: eGFR(ml/min/1.73m^2)
timeFrame: eGFR will be measured at the following time points during the clinical trial: enrollment visit (V1), Week 4 (V2), and Week 16 (V5).
measure: ECG PR Interval
timeFrame: ECG PR Interval will be measured at the following time points during the clinical trial: enrollment visit (V1), Week 4 (V2), and Week 16 (V5).
measure: ECG QRS Complex
timeFrame: ECG QRS Complex will be measured at the following time points during the clinical trial: enrollment visit (V1), Week 4 (V2), and Week 16 (V5).
measure: ECG QT Interval
timeFrame: ECG QT Interval will be measured at the following time points during the clinical trial: enrollment visit (V1), Week 4 (V2), and Week 16 (V5).
measure: ECG P Wave
timeFrame: ECG P Wave will be measured at the following time points during the clinical trial: enrollment visit (V1), Week 4 (V2), and Week 16 (V5).
measure: ECG ST Segment
timeFrame: ECG ST Segment will be measured at the following time points during the clinical trial: enrollment visit (V1), Week 4 (V2), and Week 16 (V5).
measure: ECG T Wave
timeFrame: ECG T Wave will be measured at the following time points during the clinical trial: enrollment visit (V1), Week 4 (V2), and Week 16 (V5).
measure: Adverse events and adverse reactions
timeFrame: Adverse events and adverse reactions will be measured at the following time points during the clinical trial: enrollment visit (V1), Week 4 (V2), Week 8 (V3), Week 12 (V4), and Week 16 (V5).
measure: White Blood Cell Count (WBC, 10^9/L)
timeFrame: White Blood Cell Count will be measured at the following time points during the clinical trial: enrollment visit (V1), Week 4 (V2), and Week 16 (V5).
measure: Absolute Neutrophil Count
timeFrame: Absolute Neutrophil Count will be measured at the following time points during the clinical trial: enrollment visit (V1), Week 4 (V2), and Week 16 (V5).
measure: Absolute Lymphocyte Count
timeFrame: Absolute Lymphocyte Count will be measured at the following time points during the clinical trial: enrollment visit (V1), Week 4 (V2), and Week 16 (V5).
measure: Red Blood Cell Count (RBC, 10^12/L)
timeFrame: Red Blood Cell Count will be measured at the following time points during the clinical trial: enrollment visit (V1), Week 4 (V2), and Week 16 (V5).
measure: Hemoglobin (Hb, g/L)
timeFrame: Hemoglobin will be measured at the following time points during the clinical trial: enrollment visit (V1), Week 4 (V2), and Week 16 (V5).
measure: Platelet Count (PLT, 10^9/L)
timeFrame: Platelet Count will be measured at the following time points during the clinical trial: enrollment visit (V1), Week 4 (V2), and Week 16 (V5).
measure: diabetes self-care activities scale(SDSCA)
timeFrame: Participants will complete the SDSCA at baseline (V1) and at the end of the treatment period(Week 16 ,V5).
Other outcomes:
Locations:
city: Wuhan
country: China
facility: Tongji Hospital
state: Hubei
Study officials:
affiliation: Tongji Hospital
name: Gang Yuan, Professor
role: PRINCIPAL_INVESTIGATOR
References: