Clinical trial NCT04341571: Effect of Probiotics Versus Metformin on Glycemic Control, Insulin Sensitivity and Insulin Secretion in Prediabetes.
Official title: Effect of the Administration of Probiotics Versus Metformin on Glycemic Control, Insulin Sensitivity and Insulin Secretion in Patients With Prediabetes.
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: PreDiabetes
Impaired Glucose Tolerance
Hyperglycemia
Resistance, Insulin
Keywords: Probiotics
Prediabetes
Hyperglycemia
Impaired Fasting Glucose
Glucose intolerance
Metformin
Lead sponsor: University of Guadalajara
Sponsor class: OTHER
First posted: 2020-04-10
Enrollment: 30
Sex: ALL
Minimum age (years): 31
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Double-blind, controlled clinical trial
Primary purpose: TREATMENT

Brief summary: Pre diabetes (PD) is a term that refers to alterations in blood glucose levels, including impaired fasting glucose (IFG), impaired glucose tolerance (IGT) or both, and increase in glycated hemoglobin (HbA1c), all this factors involving a higher risk to develop type 2 diabetes mellitus (T2DM).

The efficacy of pharmacotherapy in the prevention of diabetes in adults with pre diabetes has been demonstrated, the first line of pharmacology treatment is metformin, on the other hand, probiotics administration has been reported to be one of the most widely used approaches to modulate the gut microbiota and subsequently prevent or delay the incidence of T2DM.

Probiotics are live microorganisms which when administered in adequate amounts confer a health benefit on the host. Has been demonstrated the hypoglycemic effects of the probiotics in different clinical trials in type 2 diabetes mellitus and pre diabetes, but no yet compared with metformin, for this reason comparing it´s activity against metformin in pre diabetes would provide impact information on a new alternative treatment compared with the standard pharmacological treatment.

The aim of the study is evaluate the effect of administration of probiotic versus metformin on glycemic control, insulin secretion and insulin sensitivity in patients with pre diabetes.

Detailed description: A randomized, double-blind controlled clinical trial in 30 patients between 31 to 60 years of age with a diagnosis of prediabetes (IFG 100 a 125 mg/dL, IGT 140 a 199 mg/dL, HbA1c 5.7 a 6.4%) in accordance with the American Diabetes Association without treatment.

Patients with one or more of the following criteria will be excluded: History of liver, kidney or heart disease; systolic blood pressure ≥ 140 mmHg, diastolic blood pressure ≥ 90 mmHg, HbA1c ≥6.5%, triglycerides ≥ 400 mg/dL, total cholesterol ≥240 mg/dL; pregnancy or lactation; consumption of medications or supplements with effects on glucose levels.

They will be assigned randomly two groups of 15 patients; one of the groups will receive 750 mg of metformin twice at day (before breakfast and dinner) for 13 weeks.

The other group will receive 400 mg of probiotics 1 time at day (before breakfast) and placebo pill (before dinner) for 13 weeks.

They will be measured fasting blood glucose, postprandial glucose levels and glycosylated hemoglobin, and will be calculated area under curve of glucose an insulin, total insulin secretion (Insolinogenic index), first-phase of insulin secretion (Strumvoll index) and insulin sensitivity (Matsuda index).

This protocol It´s already approved by the local ethics committee and written informed consent it´s going to be obtained from all volunteers.

Statistical analysis will be presented through measures of central tendency and dispersion, average and deviation standard for quantitative variables; frequencies and percentage for qualitative variable. Will be used Wilcoxon range test for identification of differences between baseline and final evaluation of each intervention group, Mann-Whitney U Test and Wilcoxon Test for the within-groups differences. It will be considered satitistical significance p \>0.05.

Eligibility criteria: Inclusion Criteria:

* Patients both sexes
* Age between 31 and 60 years
* Diagnosis of prediabetes according ADA criteria (fasting blood glucose levels between 100-125 mg/dL, postprandial blood glucose levels after an oral glucose tolerance test with 75 g of oral glucose between 140-199 mg/dL and glycated hemoglobin between 5.7-6.4 %)
* Body Mass Index from 25 to 34.9 kg/m2
* Stable weight at least the previous last 3 months (weight variation less than 10%)
* Acceptance and signing of informed consent

Exclusion Criteria:

* History of kidney, liver or heart disease
* Women with confirmed or suspected pregnancy
* Women under lactation and/or puerperium
* Physical impossibility for taking pills
* Hypersensibility to ingredients of intervention
* Consumption of medications or supplements with effects on glucose levels
* Systolic blood pressure ≥ 140 mmHg
* Diastolic blood pressure ≥ 90 mmHg
* HbA1c ≥6.5%
* Triglycerides ≥ 400 mg/dL
* Total cholesterol ≥ 240 mg/dL

Primary outcomes:
measure: Fasting glucose levels
timeFrame: Baseline to week 13 (end of intervention)
measure: Postpandrial glucose levels
timeFrame: Baseline to week 13 (end of intervention)
measure: Glycosylated hemoglobin
timeFrame: Baseline to week 13 (end of intervention)
measure: Insulin sensitivity
timeFrame: Baseline to week 13 (end of intervention)
measure: Total insulin secretion
timeFrame: Baseline to week 13 (end of intervention)
measure: First phase of insuline secretion
timeFrame: Baseline to week 13 (end of intervention)
Secondary outcomes:
measure: Body weight
timeFrame: Baseline to week 13 (end of intervention)
measure: Body mass index (BMI)
timeFrame: Baseline to week 13 (end of intervention)
measure: Waist circunference
timeFrame: Baseline to week 13 (end of intervention)
measure: Blood pressure
timeFrame: Baseline to week 13 (end of intervention)
measure: Total cholesterol
timeFrame: Baseline to week 13 (end of intervention)
measure: High density lipoprotein (c-HDL)
timeFrame: Baseline to week 13 (end of intervention)
measure: Low density lipoprotein (c-LDL)
timeFrame: Baseline to week 13 (end of intervention)
measure: Very low density lipoprotein (VLDL)
timeFrame: Baseline to week 13 (end of intervention)
measure: Fasting blood triglycerides concentration
timeFrame: Baseline to week 13 (end of intervention)
measure: Concentration of blood creatinine
timeFrame: Baseline to week 13 (end of intervention)
measure: Concentration of blood alanine aminostranferase (ALT)
timeFrame: Baseline to week 13 (end of intervention)
measure: Concentration of blood aspartate aminostranferase (AST)
timeFrame: Baseline to week 13 (end of intervention)
measure: Incidence of treatment-Emergent Adverse Events
timeFrame: Baseline to week 13 (continuous surveiilance)
Other outcomes:
Locations:
city: Guadalajara
country: Mexico
facility: INSTITUTO DE TERAPÉUTICA EXPERIMENTAL Y CLÍNICA. Centro Universitario de Ciencias de la Salud
state: Jalisco
Study officials:
affiliation: University of Guadalajara
name: KARINA G PÉREZ-RUBIO, PhD
role: PRINCIPAL_INVESTIGATOR
References: