Effect of Berberine Versus Metformin on Glycemic Control, Insulin Sensitivity and Insulin Secretion in Prediabetes

Sponsor

University of Guadalajara (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT03029390

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

0.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Pre diabetes (PD) is a term that refers to alterations in glucose homeostasis, including impaired fasting glucose (IFG), Imparied glucose tolerance (IGT) or both, involving a higher risk to develop type 2 diabetes mellitus (T2DM) in 10 years.

The efficacy of pharmacotherapy in the prevention of diabetes in adults with prediabetes has been demonstrated, the first line of pharmacology treatment is metformin, on the other hand, the traditional Chinese and Ayurverica medicine offer potential active substances for the treatment of hyperglucemia like berberine.

Berberine is an extract with hypoglycemic effects in animal models as well as in clinical trials in type 2 diabetes mellitus even compared to metformin, for this reason comparing it's activity against metformin in prediabetes would provide impact information on a new alternative treatment and compare with the standard pharmacological treatment.

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

The investigators hypothesis is that the administration of berberine versus metformin modifies glycemic control, insulin sensitivity and insulin secretion in patients with prediabetes.

Condition or Disease	Intervention/Treatment	Phase
Prediabetes Impaired Fasting Glucose Impaired Glucose Tolerance	Dietary Supplement: Berberine Drug: Metformin	Phase 4

Detailed Description

A randomized, double-blind, placebo-controlled clinical trial in 28 patients with a diagnosis of prediabetes (IFG and IGT) in accordance with the American Diabetes Association with out treatment.

They will be assigned randomly two groups of 14 patients, one of the groups will receive 850 mg of metformin twice at day (before breakfast and before dinner) and one pill of placebo (before lunch) for 14 weeks. There will be a running period, starting with a dose of 500 mg the first week, the second week increasing to 1000 mg and from the third to the fourteenth week will be a dose of 1500 mg.

The other group will receive 500 mg of berberine three times at day (each one before the mealtime) for14 weeks. There will be a running period, starting with a dose of 850 mg the first week, the second week dose of 850 mg of metformin plus one placebo pill and from the third week to the fourteenth week will be a dose of 1700 mg ( two 850 mg metformin pills) plus one placebo pill.

They will be measured fasting blood glucose, postprandial glucose levels and glycosylated hemoglobin, and will be calculated Area Under Curve of glucose and 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. Qualitative variables will be analyzed by X2, will be used for differences inter-group Mann-Whitney U Test and Wilcoxon Test for the within-groups differences. It will be considered statistical significance p≤0.05.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

28 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

Effect of Administration of Berberine Versus Metformin on Glycemic Control, Insulin Sensitivity and Insulin Secretion in Patients With Prediabetes

Study Start Date :

Mar 1, 2016

Actual Primary Completion Date :

Feb 1, 2018

Anticipated Study Completion Date :

Jul 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Berberine hydrochloride Berberine capsules, 500 mg, three per day before each meal during 12 weeks. The patients will have a forced titration period: First week they will receive one 500 mg capsule before breakfast Second week they will receive two 500 mg capsules (before breakfast and meal) From the third week until the end of the study, they will be receive three 500 mg capsules (before each meal)	Dietary Supplement: Berberine Berberine capsules, 500 mg, three per day before each meal during 14 weeks. The patients will have a running period during two weeks: First week they will receive one 500 mg capsule before breakfast Second week they will receive two 500 mg capsules (before breakfast and meal) From the third week until the end of the study (14 week), they will be receive three 500 mg Other Names: Berberine hydrochloride
Experimental: Metformin Metformin capsules, 850 mg, two per day before breakfast and dinner and one placebo capsule before lunch during 12 weeks. The patients will have a forced titration period: First week they will receive one 850 mg capsule before breakfast Second week they will receive one 500 mg capsules (before breakfast) and one placebo capsule (before meal). From the third week until the end of the study, they will be receive two 850 mg capsules (before breakfast and dinner) and one placebo capsule (before meal).	Drug: Metformin Metformin capsules, 850 mg, two per day before breakfast and dinner and one placebo capsule before lunch during 14 weeks. The patients will have a running period: First week they will receive one 850 mg capsule before breakfast Second week they will receive one 500 mg capsules (before breakfast) and one placebo capsule (before meal). From the third week until the end of the study (14 week), they will be receive two 850 mg capsules (before breakfast and dinner) and one placebo capsule (before meal).

Arm

Intervention/Treatment

Experimental: Berberine hydrochloride

Berberine capsules, 500 mg, three per day before each meal during 12 weeks. The patients will have a forced titration period: First week they will receive one 500 mg capsule before breakfast Second week they will receive two 500 mg capsules (before breakfast and meal) From the third week until the end of the study, they will be receive three 500 mg capsules (before each meal)

Dietary Supplement: Berberine

Berberine capsules, 500 mg, three per day before each meal during 14 weeks. The patients will have a running period during two weeks: First week they will receive one 500 mg capsule before breakfast Second week they will receive two 500 mg capsules (before breakfast and meal) From the third week until the end of the study (14 week), they will be receive three 500 mg

Other Names:

Berberine hydrochloride

Experimental: Metformin

Metformin capsules, 850 mg, two per day before breakfast and dinner and one placebo capsule before lunch during 12 weeks. The patients will have a forced titration period: First week they will receive one 850 mg capsule before breakfast Second week they will receive one 500 mg capsules (before breakfast) and one placebo capsule (before meal). From the third week until the end of the study, they will be receive two 850 mg capsules (before breakfast and dinner) and one placebo capsule (before meal).

Drug: Metformin

Metformin capsules, 850 mg, two per day before breakfast and dinner and one placebo capsule before lunch during 14 weeks. The patients will have a running period: First week they will receive one 850 mg capsule before breakfast Second week they will receive one 500 mg capsules (before breakfast) and one placebo capsule (before meal). From the third week until the end of the study (14 week), they will be receive two 850 mg capsules (before breakfast and dinner) and one placebo capsule (before meal).

Outcome Measures

Primary Outcome Measures

Fasting glucose levels [Baseline to week 14]
The fasting glucose levels will be evaluated at baseline and week 14 with enzymatic/ colorimetric techniques and the entered values reflect the fasting glucose level at week 14
postprandial glucose levels [baseline to week 14]
Postprandial glucose will be evaluated at baseline week 14 after a oral glucose tolerance test with enzymatic/ colorimetric techniques and the entered values reflect the insulin sensitivity at week 14
Glycosylated hemoglobin [baseline to week 14]
Glycosylated hemoglobin will be evaluated at baseline and week 14 by Elisa and the entered values reflect the glycosylated hemoglobin at week 14
Total insulin secretion [baseline to week 14]
Total insulin secretion will be calculated at baseline and week 14 with insulinogenic index and the entered values reflect the total insulin secretion at week 14
First phase of insulin secretion [baseline to week 14]
The first phase of insulin secretion will be calculated at baseline and week 14 with Strumvoll index and the entered values reflect the first phase of insulin secretion at week 14
Insulin sensitivity [baseline to week 14]
Insulin sensitivity will be calculated at baseline and week 14 with Matsuda index and the entered values reflect the insulin sensitivity at week 14

Secondary Outcome Measures

Body Weight [Baseline to week 14]
The body weight will be measured at baseline, week 3, week 6, week 10, and week 14 with a bioimpedance balance and the entered values reflect the body weight at week 14
Body Mass Index [Baseline to week 14]
Body Mas Index will be calculated at baseline, week 3, week 6, week 10, and week 14 with the Quetelet index formula and the entered values reflect the body mass index at week 14
Body fat percentage [Baseline to week 14]
Body fat percentage will be evaluated at baseline, week 3, week 6, week 10, and week 14 by Bioimpedance technique and the entered values reflect the body fat percentage at week 14
Waist circumference [Baseline to week 14]
Waist circumference will be evaluated at baseline, week 3, week 6, week 10 and week 14 by World Health Organization technique and the entered values reflect the waist circumference mesure at week 14
Blood pressure [Baseline to week 14]
Blood pressure will be measured at baseline,week 3, week 6, week 10 and week week 14 with a digital sphygmomanometer and the entered values reflect the blood pressure at week 14
Total cholesterol [Baseline to week 14]
Total cholesterol levels will be evaluated at baseline and week 14 by enzymatic/colorimetric techniques and the entered values reflect the total cholesterol level at week 14
Triglycerides levels [Baseline to week 14]
Triglycerides levels will be evaluated at baseline and week 14 with enzymatic/colorimetric techniques and the entered values reflect the triglycerides level at week 14
High density lipoprotein (c-HDL) levels [Baseline to week 14]
c-HDL levels will be evaluated at baseline and week 14 with enzymatic/colorimetric techniques and the entered values reflect the c-HDL level at week 14
Low density lipoprotein (c-LDL) levels [Baseline to week 14]
c-LDL levels will be will be calculated at baseline and week 14 with Friedewald Formula and the entered values reflect the c-HDL level at week 14
Alanine aminotransferase (ALT) levels [Baseline to week 14]
ALT levels will be evaluated at baseline and week 14 with enzymatic/colorimetric techniques
Aspartate aminotransferase (AST) levels [Baseline to week 14]
AST levels will be evaluated at baseline and week 14 with enzymatic/colorimetric techniques
Creatinine levels [Baseline to week 14]
Creatinine levels will be evaluated at baseline and week 14 with enzymatic/colorimetric techniques

Eligibility Criteria

Criteria

Ages Eligible for Study:

31 Years to 60 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients both sexes
Age between 31 and 60 years
Diagnosis of prediabetes according 2 ADA criteria (fasting blood glucose levels between 100-125 mg/dl and postprandial blood glucose levels after an oral glucose tolerance test with 75 of oral glucose between 140-199 mg/dl)
Body Mass Index from 25 to 34.9kg/m2
Informed consent signed

Exclusion Criteria:

Women with confirmed or suspected pregnancy
Women under lactation and/or puerperium
Hypersensibility to ingredients of intervention
Physical impossibility for taking pills
Known uncontrolled renal, hepatic, heart or thyroid diseased
Diabetes diagnosis
Previous treatment for glucose
Body Mass Index ≥35 kg/m2
Glycosylated hemoglobin > 6.5%
Triglycerides ≥500 mg/dL
Total cholesterol ≥240 mg/dL
Low density lipoprotein (c-LDL) ≥190 mg/dL
Blood Pressure ≥140/90 mmHg

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Instituto de Terapeútica Experimental y Clínica. Centro Universitario de Ciencias de la Salud. Universidad de Guadalajara	Guadalajara	Jalisco	Mexico	44340