To Evaluate the Beneficial Effect of Probiotics on DKD Patients and the Role of Gut Microbiota Modulation

Diabetic Kidney Disease Clinical Trial

Official title:

To Evaluate the Clinical Efficacy of Probiotic in Patients With DKD

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05674981
• Other study ID #: DKD2022
• Status: Recruiting
• Phase: N/A
• Start date: April 24, 2023
• Est. completion date: January 31, 2025

Study information

• Verified date: May 2024
• Source: GenMont Biotech Incorporation
• Contact: Fang-Kuei Lin, Master
• Phone: +886-6-505-2151
• Email: meitung[@]genmont.com.tw
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

To evaluate the efficacy of probiotics in the treatment of diabetic kidney disease, this study is designed to explore after consumption of probiotics lactobacillus reuteri ADR-1 and lactobacillus rhamnosus GM-020 composite strain powder sachets for 6 months, whether the improvement of blood sugar, kidney related indicators can further improve the course of diabetic kidney disease. The clinical trial predicted that probiotics can improve diabetic kidney disease by changing the intestinal flora by inhibiting harmful bacteria, reduction of systemic oxidative stress, balance carbohydrate and fat metabolism, further preventing the progress of diabetic kidney disease.

Description:

WHO predicts that diabetes will become the seventh leading cause of death in 2030. This disease usually causes complications including hypertension, diabetic kidney disease, neuropathy, skin infection, and a high risk of blindness and so on. It demonstrated that probiotics have beneficial effects on several disorders; these beneficial effects include a reduction in allergic symptoms, a decrease in serum cholesterol levels, the prevention of obesity, and an improvement of the digestive system. In recent years, many studies have pointed out that Lactobacillus affects the progression of diabetes kidney disease by controlling blood sugar. From 2017 to 2020, 8 clinical trials conducted related research to explore the clinical benefits of probiotics on diabetic kidney disease. It was found that the indicators related to kidney function have ameliorated significantly, including improving glomerular function, blood sugar control, insulin metabolism, inflammatory substances in serum, and even oxidative stress factors, etc.

In a previous study, Lactobacillus strain ADR-1 was selected to verify the efficacy by utilizing HFD (High-fructose-fed) rats model, the result shows reductions in serum HbA1c and liver injury after oral gavage for 14 weeks. Afterward, a double-blind, randomized, placebo-group human clinical trial was conducted, recruiting 68 subjects with type 2 diabetes to evaluate the intestinal flora and blood sugar-related indicators, among which the metabolic indicators had significant changes. After taking it for 3 and 6 months, HbA1c and cholesterol were significantly reduced compared to the Placebo group, it was also found that the L.reuteri flora had a significant increase in the intestinal flora while the same pattern was found in the Bifidobacterium flora accordingly. This result represents the development of a positive correlation between Lactobacillus and Bifidobacterium for the intestinal flora. Furthermore, GM-020 has been proved by mouse model experiments to slow down kidney diseases, including the improvement of related indicators of renal function, serum urea nitrogen (BUN), and creatinine (Creatinine), and it shows dose-dependent variation. The combination of these two strains of probiotics is predicted to improve the metabolical index of diabetic kidney disease.

This clinical trial will explore the health-promoting effect of probiotics on patients with diabetic kidney disease, and fully explore how probiotics can improve the good bacteria and reduce the bad bacteria by changing the intestinal flora to achieve anti-inflammatory effects, Chronic inflammation, reduce systemic oxidative stress, balances carbohydrate and fat metabolism, and prevents the progression of diabetic kidney disease.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: January 31, 2025
• Est. primary completion date: January 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 25 Years to 80 Years

Eligibility

Inclusion Criteria:

• Age between 25 and 80 years old

• Suffering from type 2 diabetes and stable medication for 3 months

• Detection of HbA1c before meals between 7% and 10%

• Stage 1-3a diabetic nephropathies (eGFR > 45 mL/min)

• Microalbuminuria estimated between 30 to 300 mg/day

Exclusion Criteria:

• Patients with Type I Diabetes Mellius

• Patients with inflammatory bowel disease, liver disease, liver cirrhosis, systemic lupus erythematosus, malignancy, and high blood pressure.

• Patients with hypoglycemic coma, Diabetic ketoacidosis, hyperosmolar non-ketotic diabetic coma, or diabetes mellitus acute complications.

• Acute infection medical history in past 3 month

• Fasting blood glucose >13.3 mmol/L

• GPT>100U/L (2.5 times than usual situation)

• Vulnerable population (Including breeding or pregnant women, prisoner, aboriginal, disabled population)

• Smoker or Alcoholic

• Taking Antibiotics in past 1 month

• Stably taking probiotics supplements in past 1 months (Yogurt or dairy products were excluded)

• Taking immunosuppressive drug, angiotensin-converting enzyme inhibitors, or angiotensin receptor blockers in past 3 months

Related Conditions & MeSH terms

• Diabetic Kidney Disease
• Diabetic Nephropathies
• Kidney Diseases

Intervention

Dietary Supplement:
• Probiotic group
Two-strain probiotic supplement includes Lactobacillus reuteri ADR-1 (alive) and Lactobacillus rhamnosus GM-020 ( alive).

Other:
• Placebo group
Same additives to Probiotic group but replace probiotics with corn starch and Maltodextrin.

Locations

Country	Name	City	State
Taiwan	Chung Shan Medical University Hospital	Taichung City

Sponsors (2)

Lead Sponsor	Collaborator
GenMont Biotech Incorporation	Chung Shan Medical University

Country where clinical trial is conducted

Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline in Cys-C (Cystatin C) level at 3 months	Blood samples will be collected to examine the variation of Cys-C (Cystatin C) from baseline at 3 months.	3 months
Primary	Change from baseline in Cys-C (Cystatin C) level at 6 months	Blood samples will be collected to examine the variation of Cys-C from baseline at 6 months.	6 months
Secondary	Change from baseline in BMI (Body Mass Index) at 3 months	BMI will be calculated with weight and height combined in kg/m^2.	3 months
Secondary	Change from baseline in BMI (Body Mass Index) at 6 months	BMI will be calculated with weight and height combined in kg/m^2.	6 months
Secondary	Change from baseline in Waist and hip circumference at 3 months	Waist and hip circumference will take down in centimeters.	3 months
Secondary	Change from baseline in Waist and hip circumference at 6 months	Waist and hip circumference will take down in centimeters.	6 months
Secondary	Change from baseline in blood pressure at 3 months	The unit of measurement of blood pressure is mmHg. Both systolic and diastolic blood pressure will be measured.	3 months
Secondary	Change from baseline in blood pressure at 6 months	The unit of measurement of blood pressure is mmHg. Both systolic and diastolic blood pressure will be measured.	6 months
Secondary	Change from baseline in levels of FPG (Fasting Plasma Glucose) at 3-months	Fasting blood samples will be collected to examine variation in FPG in uIU/mL.	3 months
Secondary	Change from baseline in levels of FPG at 6-months	Fasting blood samples will be collected to examine variation in FPG in uIU/mL.	6 months
Secondary	Change from baseline in levels of serum insulin at 3-months	Fasting blood samples will be collected to examine variation in serum insulin in uIU/mL.	3 months
Secondary	Change from baseline in levels of serum insulin at 6-months	Fasting blood samples will be collected to examine variation in serum insulin in uIU/mL.	6 months
Secondary	Change from baseline in levels of HbA1c (Hemoglobin A1C) at 3-months	Fasting blood samples will be collected to investigate the levels of HbA1c in %.	3 months
Secondary	Change from baseline in levels of HbA1c at 6-months	Fasting blood samples will be collected to investigate the levels of HbA1c in %.	6 months
Secondary	Change from baseline in levels of HOMA-IR (Homeostatic Model Assessment for Insulin Resistance) at 3-months	The equation of HOMA-IR=(insulin (mIU/L) and glucose (mg/dL))/405)	3 months
Secondary	Change from baseline in levels of HOMA-IR at 6-months	The equation of HOMA-IR=(insulin (mIU/L) and glucose (mg/dl))/405)	6 months
Secondary	Change from baseline in levels of HOMA-ß (Homeostatic Model Assessment for ß-cell function) at 3-months	The equation of HOMA-ß=20 × fasting insulin (µIU/ml)/fasting glucose (mmol/ml) - 3.5	3 months
Secondary	Change from baseline in levels of HOMA-ß (Homeostatic Model Assessment for ß-cell function) at 6-months	The equation of HOMA-ß=20 × fasting insulin (µIU/ml)/fasting glucose (mmol/ml) - 3.5	6 months
Secondary	Change from baseline in levels of QUICKI (Quantitative Insulin Sensitivity Check Index) at 3-months	The equation of QUICKI=1 / [log(Fasting Insulin (µU/ml) + log(Fasting Glucose (mg/dL))]	3 months
Secondary	Change from baseline in levels of QUICKI (Quantitative Insulin Sensitivity Check Index) at 6-months	The equation of QUICKI=1 / [log(Fasting Insulin (µU/ml) + log(Fasting Glucose (mg/dL))]	6 months
Secondary	Change from baseline in the level of GA (Glycated albumin) at 3-months	Blood samples will be collected to examine changes in GA in mg/dL.	3 months
Secondary	Change from baseline in the level of GA (Glycated albumin) at 6-months	Blood samples will be collected to examine changes in GA in mg/dL.	6 months
Secondary	Change from baseline in the level of CRE (Creatinine) at 3-months	Blood samples will be collected to examine changes in CRE in mg/dL.	3 months
Secondary	Change from baseline in the level of CRE at 6-months	Blood samples will be collected to examine changes in CRE in mg/dL.	6 months
Secondary	Change from baseline in the level of BUN (Blood Urea Nitrogen) at 3-months	Blood samples will be collected to examine changes in BUN in mg/dL.	3 months
Secondary	Change from baseline in the level of BUN at 6-months	Blood samples will be collected to examine changes in BUN in mg/dL.	6 months
Secondary	Change from baseline in the level of K+ (Potassium) at 3-months	Blood samples will be collected to examine changes from baseline in K+ in mg/dL.	3 months
Secondary	Change from baseline in the level of K+ at 6-months	Blood samples will be collected to examine changes from baseline in K+ in mg/dL.	6 months
Secondary	Change from baseline in the level of Urine protein/albumin at 3-months	Urine samples will be collected to examine changes in Urine protein/albumin in mg/dL.	3 months
Secondary	Change from baseline in the level of Urine protein/albumin at 6-months	Urine samples will be collected to examine changes in Urine protein/albumin in mg/dL.	6 months
Secondary	Change from baseline in the level of Urine microalbuminuria/creatinine at 3-months	Urine samples will be collected to examine changes from baseline in Urine protein/albumin in mg/dL.	3 months
Secondary	Change from baseline in the level of Urine microalbuminuria/creatinine at 6-months	Urine samples will be collected to examine changes from baseline in Urine protein/albumin in mg/dL.	6 months
Secondary	Change from baseline in the level of Urine acid at 3-months	Urine samples will be collected to examine changes in Urine protein/albumin in mg/dL.	3 months
Secondary	Change from baseline in the level of Urine acid at 6-months	Urine samples will be collected to examine changes in Urine protein/albumin in mg/dL.	6 months
Secondary	Change from baseline in the level of CG (The Cockcroft and Gault formula) at 3-months	CG will be calculated with creatinine, age, weight, gender. The equation of CG = (((140 - age in years) x (weight in kg)) x 1.23) / (serum creatinine in micromol/l).	3 months
Secondary	Change from baseline in the level of CG at 6-months	CG will be calculated with creatinine, age, weight, gender. The equation of CG = (((140 - age in years) x (weight in kg)) x 1.23) / (serum creatinine in micromol/l).	6 months
Secondary	Change from baseline in the level of eGFR (Estimated Glomerular Filtration Rate) at 3-months	eGFR will be estimated according to the CKD-EPI Creatinine Equation (2021) which is calculated with serum creatinine, Cystatin C, age, gender.	3 months
Secondary	Change from baseline in the level of eGFR (Estimated Glomerular Filtration Rate) at 6-months	eGFR will be estimated according to the CKD-EPI Creatinine Equation (2021) which is calculated with serum creatinine, Cystatin C, age, gender.	6 months
Secondary	Change from baseline in levels of blood lipid-related Index at 3 months	Blood samples will be collected to examine variation in TG (Triglyceride), TC (Total Cholesterol), VLDL (Very-Low-Density Lipoprotein), LDL (Low-density lipoprotein), HDL (High-density lipoprotein).	3 months
Secondary	Change from baseline in levels of blood lipid-related Index at 6 months	Blood samples will be collected to examine variation in TG (Triglyceride), TC (Total Cholesterol), VLDL (Very-Low-Density Lipoprotein), LDL (Low-density lipoprotein), HDL (High-density lipoprotein).	6 months
Secondary	Change from baseline in levels of cytokines Index at 3 months	Blood samples will be collected to examine variation in hs-CRP (high-sensitivity C-reactive protein), IL-6 (Interleukin-6), IL-18 (Interleukin-18), IL -1-a (Interleukin-1-a), IL-1ß (Interleukin-1 ß), TNF-a (Tumor necrosis factor-a), NGAL (Neutrophil Gelatinase-Associated Lipocalin), sTNFR1 (Soluble tumour necrosis factor receptor-1), PGRN (Progranulin). All the indexes will be recorded in in pg/mL.	3 months
Secondary	Change from baseline in levels of cytokines Index at 6 months	Blood samples will be collected to examine variation in hs-CRP, IL-6, IL-18, IL-1-a, IL-1ß, TNF-a, NGAL, sTNFR1, PGRN. All the indexes will be recorded in in pg/mL.	6 months
Secondary	Change from baseline in levels of TIBC (Total Iron-Binding Capacity) at 3-months	TIBC will be calculated by summing the values of serum iron and UIBC(unsaturated iron-binding capacity) which is examed from blood samples.	3 months
Secondary	Change from baseline in levels of TIBC at 6-months	TIBC will be calculated by summing the values of serum iron and UIBC which is examed from blood samples.	6 months
Secondary	Change from baseline in the level of SCFA (Short Chain Fatty Acids) at 6 months	Stool samples will be collected to examine variation in SCFA (Short Chain Fatty Acids).	6 months
Secondary	Change from baseline in the level of TMAO (Trimethylamine N-oxide) at 3-months	Blood samples will be collected to examine variation in TMAO in µmol/L.	3 months
Secondary	Change from baseline in the level of TMAO at 6-months	Blood samples will be collected to examine variation in TMAO in µmol/L.	6 months
Secondary	Change from baseline in self-record of the International physical activity questionary (IPAQ) in physical assessment at 6 months	The questionnaire will be recorded the laborious activity by the subject himself/herself before and after the treatment.	6 months
Secondary	Change from baseline in gut microbiota at 6 months	The analysis of Gut microbiota will utilize DNA sequencing to investigate the intestinal microbiota through stool samples.	6 months