The Effect of Single Probiotic on Metabolic Control in Type 2 Diabetes

Diabetes Mellitus, Type 2 Clinical Trial

Official title:

The Effects of Single Probiotic on Glycemic Control, Lipid Profile, Some of Inflammatory Cytokines and Gene Expression Levels in Type 2 Diabetic Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05066152
• Other study ID #: IstanbulU-BTipici-001
• Status: Completed
• Phase: N/A
• Start date: February 1, 2016
• Est. completion date: October 2, 2017

Study information

• Verified date: September 2021
• Source: Istanbul University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Recent studies indicate that dysbiosis of intestinal microbiota and low grade inflammation are important pathogenic determinants of type 2 diabetes (T2DM), which has increased in epidemic size over the last 20 years. Probiotics have been used in T2DM for the modification of IM and anti-inflammatory effects. However, effect of probiotics on metabolic control in T2DM are inconsistent. Present study will be designed to determine the effects of Lactobacillus GG (LGG) on glycemic control, lipid profile, inflammation parameters and expression of certain genes linked to T2DM. This study will be conducted at the Istanbul Faculty of Medicine, a tertiary care diabetes outpatient clinic and should involve 34 T2DM subjects. Subjects will be randomly assign to receive either LGG probiotic drop or a placebo.In this placebo controlled trial, effect of single strain probiotic vs. placebo on metabolic control and certain genes linked to T2DM will be assessed.

Description:

Evidence-based data showed that intestinal microbiota (IM) plays a role in the development of metabolic diseases. Recent studies have reported that dysbiosis of IM and low-grade inflammation is effective in pathogenesis of type 2 diabetes mellitus (T2DM), which has increased in epidemic size over the last 20 years. Firmicutes, Bacteroidetes and Proteobacteria's ratios in obese and T2DM patients were found to be different than healthy subjects. In these cases, there is an association between increasing the proportion of gram-negative bacteria in the intestines and subclinical inflammation. Probiotics are live microorganisms that are intended to have health benefits by regulating mucosal and systemic immunity, when consumed as a nutritional supplement. There are studies investigating the effects of probiotic use on insulin sensitivity, glycemic control, lipid profile and inflammatory parameters in patients with T2DM. However, several probiotic strains were used frequently in these studies, or probiotics and prebiotics were given as cocktails. Their effects might be together or even synergistic. Lactobacillus rhamnosus GG (or Lactobacillus GG: LGG) is a widely used probiotic microorganism. Studies have shown that LGG prevents diarrhea and atopic dermatitis, provides antitumor activity, improves the immune system, and lowers serum cholesterol levels. However, there is a limited data about the effects of LGG on the glycemic control of diabetic animal models but human studies are scarce. Therefore, present study is designed to determine the effects of LGG on glycemic control, lipid profile, inflammation parameters, and expression of certain genes linked to T2DM. Subjects will be randomly assign to receive probiotic "Lactobacillus Rhamnosus GG (ATCC 53103)" or placebo for 8-weeks administered as a drop formulation. Patients in the intervention group receive 10 probiotic drops (1x1010 cfu LGG) once daily with breakfast. Subjects will be contacted via telephone every week for an assessment of adverse events and probiotic/placebo compliance. Fasting blood samples will be taken at baseline and post treatment to measure carbohydrate metabolism (glucose, insulin, fructosamine and HbA1c), lipid profile (triglycerides; total, HDL- and LDL-cholesterol) and biomarkers of inflammation (hs-CRP and IL-6). TLR2, TLR4, MUC2 and MUC3A genes expressions will be investigated on stool samples at baseline and post treatment. Stool samples will be stored at -80°C until RNA isolation.The gene expression levels will be determined by Quantitative Real Time PCR method using the determined cDNA samples. Dietary intake will be evaluated by the 3-day food record. During the 4th and 8th week of the study, a 3 day food consumption records will be taken. Diabetics will be given detailed oral and written instructions regarding the completion of food record, consisting of 2 midweek days and 1 weekend day. In order to determine the amounts of consumed foods correctly, information will be given about measuring cups such as water glass, tea glass, teaspoon, tablespoon, serving spoon, bowl. Dietary intake will be assessed using a food composition database of BEBIS programme including specific Turkish foods. All anthropometric measures will be conducted in a fasting state taken at baseline and following an 8-week intervention by experienced examiner (dietitian). Body weight and body composition will be assessed by bioelectrical impedance analysis device (Tanita BC-420 MA). Body mass index (BMI) will be calculated as weight (kg) divided by height squared (m2). Waist circumference (measured midway between lowest rib and iliac crest) will be measured using a non-stretchable measuring tape. All analysis will be performed using the Statistical Package for Social Sciences (SPSS) 21.0 package program and significance will defined as p<0.05. Descriptive statistics will be given as mean, standard deviation and median (minimum to maximum) for continuous measures. Categorical variables will be expressed as case numbers and percentage values. The Shapiro-Wilk tests will used to determine whether the distribution of continuous measures are normal. Student's t test and Mann-Whitney-U test will used for the two groups comparisons according to whether the variables showed normal distribution. Comparisons of changes in groups within themselves (before and after probiotic or placebo administration) will made using the t-test if the variances is normal, and if the Wilcoxon test is not normal in the cohort. The web-based RT2 Profiler PCR Array Data Analysis program will used to determine the change of ΔCt values obtained from the Real Time-PCR gene expression study (before and after probiotic and placebo administration). p<0.05 will be considered statistically significant.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 34
• Est. completion date: October 2, 2017
• Est. primary completion date: July 30, 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 30 Years to 60 Years

Eligibility

Inclusion Criteria:

• Clinical diagnosis of Type 2 Diabetes
• Taking oral-antidiabetic medication

Exclusion Criteria:

• Smokers,
• Alcohol drinkers,
• Inflammatory bowel or autoimmune disease,
• Immunodeficiency,
• Using anti-epileptic, incretin enhancer (DPP-4 inhibitor), insulin or insulin analogs, dietary supplements
• Systemic antibiotics within 6 weeks before inclusion
• Use of probiotics within 3 months before inclusion
• Breast-feeding or pregnancy

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2

Intervention

Dietary Supplement:
• Lactobacillus rhamnosus GG (ATCC 53103)
One probiotic drop contained a formulation of 1x109 Cfu Lactobacillus rhamnosus GG (LGG; ATCC 53103)
• Placebo
Carrier material of probiotic product, not containing bacterial strain, similar appearance as the probiotic

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Istanbul University

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	HbA1c	HbA1c %	8 weeks compared to baseline
Primary	HOMA-IR	HOMA-IR= Fasting plasma glucose (mg/dL) x Fasting plasma insulin (µU/mL)/405	8 weeks compared to baseline
Secondary	QUICKI	1/ [log (fasting plasma insulin (µU/mL)+log (fasting blood glucose (mg/dL)] [22, 23].	8 weeks compared to baseline
Secondary	Fasting plasma glucose	FPG in mg/dL	8 weeks compared to baseline
Secondary	Fructosamine	µmol/L	8 weeks compared to baseline
Secondary	HDL-C	mg/dl, HDL cholesterol	8 weeks compared to baseline
Secondary	LDL-C	mg/dl, LDL cholesterol	8 weeks compared to baseline
Secondary	Triglycerides	mg/dl	8 weeks compared to baseline
Secondary	hs-CRP	mg/dl, high sensitive c reactive protein	8 weeks compared to baseline
Secondary	IL-6	pg/mL, Interleukin 6	8 weeks compared to baseline
Secondary	TLR2	Toll-like receptor 2 gene expression	8 weeks compared to baseline
Secondary	TLR4	Toll-like receptor 4 gene expression	8 weeks compared to baseline
Secondary	MUC2	Mucin 2 gene expression	8 weeks compared to baseline
Secondary	MUC3A	Mucin 3A gene expression	8 weeks compared to baseline
Secondary	Weight	body weight, kg	8 weeks compared to baseline
Secondary	BMI	body mass index, kg/m2	8 weeks compared to baseline
Secondary	WHR	waist and hip ratio %	8 weeks compared to baseline
Secondary	Fat mass	body fat mass, kg	8 weeks compared to baseline
Secondary	Fat mass	body fat mass, %	8 weeks compared to baseline
Secondary	Lean body mass	body lean body mass, kg	8 weeks compared to baseline
Secondary	Muscle mass	body muscle mass, kg	8 weeks compared to baseline
Secondary	Total body water	kg kg and %	8 weeks compared to baseline
Secondary	Total body water	% kg and %	8 weeks compared to baseline
Secondary	Bone mass	Body bone mass, kg	8 weeks compared to baseline
Secondary	Basal metabolic rate	Acoording to bioelectrical impedance analysis device, kcal	8 weeks compared to baseline
Secondary	Energy	Energy intake, kcal	During 4th and 8th weeks
Secondary	Carbohydrate	Carbohydrate intake, gram	During 4th and 8th weeks
Secondary	Carbohydrate	Carbohydrate intake, %	During 4th and 8th weeks
Secondary	Protein	Protein intake, gram	During 4th and 8th weeks
Secondary	Protein	Protein intake, %	During 4th and 8th weeks
Secondary	Fat	Fat intake, gram	During 4th and 8th weeks
Secondary	Fat	Fat intake, %	During 4th and 8th weeks
Secondary	Dietary fiber	Dietary fiber intake, gram	During 4th and 8th weeks
Secondary	Dietary cholesterol	Dietary cholesterol intake, gram	During 4th and 8th weeks