Novel Chinese Medicine Formula for Diabetes
- Conditions
- Type 2 Diabetes
- Registration Number
- NCT06978023
- Lead Sponsor
- Chinese University of Hong Kong
- Brief Summary
Diabetes is a leading cause of heart disease, stroke, kidney failure, cancer and premature death. One in 10 adults are affected by diabetes. Early control of high blood gluocse prevents progressive deterioration and treatment escalation. People with diabetes have impaired insulin secretion, the only hormone that can lower blood glucose, or resistance to insulin action. There are trillions of microrganisms (tiny living things including bacteria) in the gut that can interact with foods and medicine to alter bodily functions including insulin secretion and its actions. Studies in animals and human suggested that a Traditional Chinese Medicine (TCM) containing a combination of four herbs (Jinmai, abbreviated as JM) reduced blood glucose by increasing insulin secretion accompanied by favorable changes in gut bacteria and expression of genetic information that regulate bodily functions.
In this study, people with type 2 diabetes diagnosed for less than 6 years and not treated with any glucose lowering drugs are assigned randomly to recieve 1) high dose JM (JM-HD) or 2) low dose JM (JM-LD) or 3) look-alike dummy (placebo) given in powder form to be dissolved in water taken twice daily for 24 weeks. We shall compare the abilities of these 3 combination products to lower blood glucose over a 2-hour period after taking a nutritional drink at 0, 12 and 24 weeks. The assigned treatment will then be discontinued for 12 weeks and the test will be repeated to see if improvement is sustained. Samples will be collected at week 0 and 24 (on-treatment) and week 36 (12 weeks off-treament) to compare changes in gut bacteria in faeces and expression of genetic information that make proteins which regulate blood glucose amongst these 3 groups.
- Detailed Description
People with impaired insulin secretion from the pancreatic beta-cells is the main cause of type 2 diabetes (T2D). This can be demonstrated by measuring insulin secretion following an 75 gram oral glucose tolerance test (OGTT) or a mixed meal tolerance test (MMTT). Other pathophysiological processes underlying diabetes include non-suppression of glucagon from pancreatic alpha-cells with increased fasting blood glucose, abnormal incretin (e.g. glucagon like peptide GLP1) secretion from gut which augment insulin secretion during food intake as well as changes in gut microbiota which can interact with foods and medicine to alter hormonal secretion and metabolic milieu. Obesity, hyperglycaemia and dyslipidemia can alter inflammatory pathways, transcription factors and oxidative stress resulting in further impairment of insulin secretion and its actions. Early attainment of glycemic control can break these vicious cycles, improve glycemic durability and reduce progressive treatment escalation.
Several randomized controlled trials (RCTs) and meta-analyses indicate that TCM containing multiple active components may prevent and control diabetes in human. In animal studies, our group first reported that a combination of extracts from 3 herbs (Coptidis Rhizoma; Astragali Radix; Lonicerae Japonicae Flos, abbreviated as CAL) lowered blood glucose in diabetic rats with sustained improvement in insulin resistance and beta-cell function accompanied by resolution of fatty liver. These effects persisted for weeks or months after treatment discontinuation depending on treatment duration. These improvements were accompanied by changes in gene expression (RNA and microRNA) implicated in energy metabolism. In another animal study, we first reported that extracts from Ophiopogonis (Oph) increased insulin secretion, reduced inflammation and expanded islet mass with lowering of blood glucose.
Based on these mechanistic studies, we designed a proprietary formula consisting of CAL plus Oph (referred as Jinmai, JM). We randomized people with prediabetes to recieve 12-week treatment with 1) CAL only, 2) CAL+Oph low dose (JM-LD), 3) CAL+Oph very low dose (JM-VLD) and 4) consultation with CM practitioners (control), followed by treatment discontinuation for 12 weeks. Amongst these 4 groups, participants treated with JM-LD had signficant reduction in blood glucose and increased insulin secretion during 75 gram OGTT. This effect was sustained after discontinuation of JM-LD for 3 months. Microbiota and RNA analysis indicated that JM-LD caused favorable changes in microbiota and gene expression which correlated with these metabolic changes.
Based on these consistent evidence, we produced a proprietary JM formula consisting of a fixed combination of extracts of CAL with low dose (JM-LD) or high dose extracts of Oph (JM-HD) under good manufacturing practice. The study was approved by the Hong Kong Department of Health for investigational use aimed at registering JM as a novel CM for prevention and treatment of T2D.
Hypothesis:
A 24-week treatment with JM in people with T2D reduce glucose excursion and improve beta-cell function through changes in gut microbiota and gene expression
Study design:
A double-blind, placebo-controlled RCT to assess the efficacy, safety and multiomic effects of JM and its optimal dose in people with early T2D (within 6 years) not treated with glucose lowering drugs.
Intervention:
Randomized in a 1:1:1 ratio to receive 24-week treatment with
1. JM-LD in powder form (13.5 g twice daily) to be dissolved in 250 ml of hot water
2. JM-HD in powder form (13.5 g twice daily) to be dissolved in 250 ml of hot water or
3. matching placebo in powder form (13.5 g twice daily) to be dissolved in 250 ml of hot water followed by treatment discontinuation for 3 months
Primary objective:
To compare changes in glucose excursion during MMTT after 24 week treatment with JM-LD or JM-HD compared to placebo
Secondary objectives:
1. To evaluate the sustained effect of JM on glucose exursion during MMTT 12 weeks after JM discontinuation compared to placebo
2. To compare changes in cardiometabolic risk factors including blood pressure, lipids and body weight and HbA1c as well as insulin secretion and resistance during MMTT after 24 weeks of JM treatment compared to placebo
3. To compare changes in biomarkers and multiomics and their correlations with metabolic changes after 24 weeks of JM treatment compared to placebo
Primary outcome measure:
Between-group difference in area-under-the-curve of plasma glucose (AUC-PG) during MMTT in the JM group versus changes in the placebo group (difference-difference) from week 0 to 24 (on treatment)
Sample size:
In the aforementioned 12-week study of JM versus placebo in people with prediabetes, the mean (SD) of AUC-PG during OGTT in placebo group was 18.9 (1.8) mmol/L/min. The AUC-PG was 1.89 mmol/L/min, i.e. 10% lower in the JM-LD group than the placebo group. Based on a conservative estimation of a superiority margin of 0.945 (5% of mean difference) in favor of JM-HD versus placebo, 45 participants in each arm are needed to achieve an 80% power at one-sided significance level of 5%. Allowing a 20% drop out rate, we shall assign 54 participants to each of 3 groups with a total of 162 participants.
Study site:
The study will be conducted at Ward 3M, Diabetes and Endocrine Research Centre, Prince of Wales Hospital in accordance with Declaration of Helsinki, and Good Clinical Practice (GCP) and Standard Operation Procedures (SOP) stipulated by the CUHK-NTEC Clinical Research Management Office
Significance of the study:
This double-blind placebo-controlled RCT will provide data in support of the beneficial effects of a novel proprietary CM formula (JM) on glycemic excursion in people with early T2D as a therapeutic option. The effects of JM on beta-cell function, insulin resistance, biomarkers, multiomics and gut microbiota will explain the mechanisms underlying the benefits of JM. These data will provide the basis for conduct of large-scale study to examine the effects of JM in the prevention of T2D and its progression to non-communicable diseases.
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 162
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Primary Outcome Measures
Name Time Method Difference-difference in glycemic excursion during MMTT after 24 weeks of JM treatment From Week-0 to Week-24 Between-group difference in changes in area under the curve of plasma glucose (AUC-PG) during 2-hour MMTT in JM group versus changes in the placebo group
- Secondary Outcome Measures
Name Time Method Difference-difference in serum alanine transferase after 24 weeks of JM treatment From Week-0 to Week-24 Between-group difference in changes in serum alanine transferase in the JM group versus changes in placebo group
Difference-difference in serum alkaline phosphatase after 24 weeks of JM treatment From Week-0 to Week-24 Between-group difference in ichanges in serum alkaline phosphatase in the JM group versus changes in placebo group
Difference-difference in serum bilirubin after 24 weeks of JM treatment From Week-0 to Week-24 Between-group difference in changes in serum bilirubin in the JM group versus changes in placebo group
Difference-difference in EQ5D index after 24 weeks of JM treatment From Week-0 to Week-24 Between-group difference in changes in EQ5D as index of quality of life in the JM group versus changes in the placebo group
Difference-difference in glycemic excursion during MMTT 12 weeks off JM treatment From Week-24 to Week-36 (off treatment) Between-group difference in AUC-PG during 2-hour MMTT in JM group versus changes in placebo group
Difference-difference in beta cell function after 24 weeks of JM treatment From Week-0 to Week-24 Between-group difference in changes in HOMA-beta in the JM group versus changes in placebo group
Difference-difference in insulin secretion after 24 weeks of JM treatment From Week-0 to Week-24 Between-group difference in changes in insulinogenic index derived from PG and insulin measured during MMTT in the JM group versus changes in placebo group
Difference-difference in insulin resistance after 24 weeks of JM treatment From Week-0 to Week-24 Between-group difference in changes in HOMA-IR in the JM group versus changes in placebo group
Difference-difference in insulin sensitivity after 24 weeks of JM treatment From Week-0 to Week-24 Between-group difference in changes in quantitative insulin sensitivity check index (QUICKI) derived from PG and insulin measured during MMTT in the JM group versus changes in placebo group
Difference-difference in body mass index (BMI) after 24 weeks of JM treatment From Week-0 to Week-24 Between-group difference in changes in BMI in JM group versus changes in placebo group
Difference-difference in blood pressure after 24 weeks of JM treatment From Week-0 to Week-24 Between-group difference in changes in blood pressure in JM group versus changes in placebo group
Difference-difference in non-HDL cholesterol after 24 weeks of JM treatment From Week-0 to Week-24 Between-group difference in changes in non-HDL cholesteroal in JM group versus changes in placebo group
Difference-difference in HbA1c after 24 weeks of JM treatment From Week-0 to Week-24 Between-group difference in changes in HbA1c in JM group versus changes in placebo group
Difference-difference in waist circumference after 24 weeks of JM treatment From Week-0 to Week-24 Between-group difference in changes in waist circumference in JM group versus changes in placebo group
Difference-difference in blood haemoglobin after 24 weeks of JM treatment From Week-0 to Week-24 Between-group difference in changes in blood haemoglobin in the JM group versus changes in placebo group
Difference-difference in estimated glomerular filtration rate (eGFR) after 24 weeks of JM treatment From Week-0 to Week-24 Between-group difference in ichanges in eGFR in the JM group versus changes in placebo group
Trial Locations
- Locations (1)
Department of Medicine and Therapeutics, The Chinese University of Hong Kong (CUHK), Ward 3M, Diabetes and Endocrine Research Centre, 3/F Day Treatment Block and Children Wards (Old Block), Prince of Wales Hospital
🇭🇰Hong Kong, Hong Kong