Clinical trial NCT05674981: To Evaluate the Beneficial Effect of Probiotics on DKD Patients and the Role of Gut Microbiota Modulation
Official title: To Evaluate the Clinical Efficacy of Probiotic in Patients with DKD
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Diabetic Kidney Disease
Keywords: Diabetic kidney disease
gut microbiota
Probiotic
Lactobacillus reuteri
Lactobacillus rhamnosus
Lead sponsor: GenMont Biotech Incorporation
Sponsor class: INDUSTRY
Collaborators: name: Chung Shan Medical University
First posted: 2023-01-09
Enrollment: 50
Sex: ALL
Minimum age (years): 25
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Parallel Assignment, Randomized Controlled Trial
Primary purpose: SUPPORTIVE_CARE

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Change from baseline in Cys-C (Cystatin C) level at 3 months
timeFrame: 3 months
measure: Change from baseline in Cys-C (Cystatin C) level at 6 months
timeFrame: 6 months
Secondary outcomes:
measure: Change from baseline in BMI (Body Mass Index) at 3 months
timeFrame: 3 months
measure: Change from baseline in BMI (Body Mass Index) at 6 months
timeFrame: 6 months
measure: Change from baseline in Waist and hip circumference at 3 months
timeFrame: 3 months
measure: Change from baseline in Waist and hip circumference at 6 months
timeFrame: 6 months
measure: Change from baseline in blood pressure at 3 months
timeFrame: 3 months
measure: Change from baseline in blood pressure at 6 months
timeFrame: 6 months
measure: Change from baseline in levels of FPG (Fasting Plasma Glucose) at 3-months
timeFrame: 3 months
measure: Change from baseline in levels of FPG at 6-months
timeFrame: 6 months
measure: Change from baseline in levels of serum insulin at 3-months
timeFrame: 3 months
measure: Change from baseline in levels of serum insulin at 6-months
timeFrame: 6 months
measure: Change from baseline in levels of HbA1c (Hemoglobin A1C) at 3-months
timeFrame: 3 months
measure: Change from baseline in levels of HbA1c at 6-months
timeFrame: 6 months
measure: Change from baseline in levels of HOMA-IR (Homeostatic Model Assessment for Insulin Resistance) at 3-months
timeFrame: 3 months
measure: Change from baseline in levels of HOMA-IR at 6-months
timeFrame: 6 months
measure: Change from baseline in levels of HOMA-β (Homeostatic Model Assessment for β-cell function) at 3-months
timeFrame: 3 months
measure: Change from baseline in levels of HOMA-β (Homeostatic Model Assessment for β-cell function) at 6-months
timeFrame: 6 months
measure: Change from baseline in levels of QUICKI (Quantitative Insulin Sensitivity Check Index) at 3-months
timeFrame: 3 months
measure: Change from baseline in levels of QUICKI (Quantitative Insulin Sensitivity Check Index) at 6-months
timeFrame: 6 months
measure: Change from baseline in the level of GA (Glycated albumin) at 3-months
timeFrame: 3 months
measure: Change from baseline in the level of GA (Glycated albumin) at 6-months
timeFrame: 6 months
measure: Change from baseline in the level of CRE (Creatinine) at 3-months
timeFrame: 3 months
measure: Change from baseline in the level of CRE at 6-months
timeFrame: 6 months
measure: Change from baseline in the level of BUN (Blood Urea Nitrogen) at 3-months
timeFrame: 3 months
measure: Change from baseline in the level of BUN at 6-months
timeFrame: 6 months
measure: Change from baseline in the level of K+ (Potassium) at 3-months
timeFrame: 3 months
measure: Change from baseline in the level of K+ at 6-months
timeFrame: 6 months
measure: Change from baseline in the level of Urine protein/albumin at 3-months
timeFrame: 3 months
measure: Change from baseline in the level of Urine protein/albumin at 6-months
timeFrame: 6 months
measure: Change from baseline in the level of Urine microalbuminuria/creatinine at 3-months
timeFrame: 3 months
measure: Change from baseline in the level of Urine microalbuminuria/creatinine at 6-months
timeFrame: 6 months
measure: Change from baseline in the level of Urine acid at 3-months
timeFrame: 3 months
measure: Change from baseline in the level of Urine acid at 6-months
timeFrame: 6 months
measure: Change from baseline in the level of CG (The Cockcroft and Gault formula) at 3-months
timeFrame: 3 months
measure: Change from baseline in the level of CG at 6-months
timeFrame: 6 months
measure: Change from baseline in the level of eGFR (Estimated Glomerular Filtration Rate) at 3-months
timeFrame: 3 months
measure: Change from baseline in the level of eGFR (Estimated Glomerular Filtration Rate) at 6-months
timeFrame: 6 months
measure: Change from baseline in levels of blood lipid-related Index at 3 months
timeFrame: 3 months
measure: Change from baseline in levels of blood lipid-related Index at 6 months
timeFrame: 6 months
measure: Change from baseline in levels of cytokines Index at 3 months
timeFrame: 3 months
measure: Change from baseline in levels of cytokines Index at 6 months
timeFrame: 6 months
measure: Change from baseline in levels of TIBC (Total Iron-Binding Capacity) at 3-months
timeFrame: 3 months
measure: Change from baseline in levels of TIBC at 6-months
timeFrame: 6 months
measure: Change from baseline in the level of SCFA (Short Chain Fatty Acids) at 6 months
timeFrame: 6 months
measure: Change from baseline in the level of TMAO (Trimethylamine N-oxide) at 3-months
timeFrame: 3 months
measure: Change from baseline in the level of TMAO at 6-months
timeFrame: 6 months
measure: Change from baseline in self-record of the International physical activity questionary (IPAQ) in physical assessment at 6 months
timeFrame: 6 months
measure: Change from baseline in gut microbiota at 6 months
timeFrame: 6 months
Other outcomes:
Locations:
city: Taichung City
country: Taiwan
facility: Chung Shan Medical University Hospital
Study officials:
affiliation: Chung Shan Medical University
name: Yi-Sun Yang, PhD
role: PRINCIPAL_INVESTIGATOR
References: