Combination of Metformin/Inulin vs Inulin on Adiponectin in Metabolic Syndrome

NCT ID: NCT02773927

Last Updated: 2016-05-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-01-31
• Study Completion Date: 2015-06-30

Brief Summary

Presence of metabolic syndrome (MetS) and its relation with insulin resistance, obesity, dyslipidemia, systemic inflammation and cardiovascular disease is of great concern. The study of certain adipokines such as adiponectin has demonstrated an inverse association with insulin resistance, especially in Latin population lower levels of adiponectin have been observed compared to other ethnic groups. It appears to be an important molecule that is involved in limiting the pathogenesis of obesity-linked disorders and may have potential benefits as a marker to evaluate the effect of possible interventions on the MetS components and its complications.

Metformin is treatment of choice in patients with MetS, due to its low cost and pharmacological comparable effects with thiazolidinediones (pioglitazone), it decreases hyperinsulinemia, insulin resistance, free fatty acids and triglycerides, it produces as well, a moderate weight loss, improves lipid profile and delays the appearance of diabetes mellitus in subjects with an abnormal fasting glucose.

A second choice to lower the risks would be the addition of a fiber like inulin, a prebiotic, since it has demonstrated metabolic benefits on lipid and carbohydrates metabolism by several mechanisms proposed such as induction of lipogenic enzymes by glucose, production of short-chained fatty acids, glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 (GLP-1), and growth of Bifidobacterium. A good natural source of inulin is the agave.

It is expected that the combination of metformin plus agave inulin will produce a beneficial impact through pharmacological synergism and that will produce changes in the pathophysiology of MetS.

Detailed Description

The main objective was to compare the effect of the administration of Metformin/agave inulin vs. Agave inulin on adiponectin in patients with MetS. The investigators conducted a double-blinded randomized trial, on 4 groups, each group with 10 male patients of 40-80 years of age with METS diagnosed by International Diabetes Federation (IDF) criteria. Randomization determined the group assignation during the 12-week trial, each group consisted of:

Group (A) Metformin plus agave inulin: 10 individuals received metformin in a dosis of 500 mg per day (1 tablet of 500 mg) plus inulin in a dosis of 10 mg per day (5 mg every 12 hours) during 12 weeks.

Group (B) Metformin plus Placebo of agave inulin: 10 individuals received Metformin in a dosis of 500mg per day (with the first bite of the second meal) plus homologue placebo of inulin (calcinated magnesia) in a dosis of 10 mg every 24 hrs (5 mg of calcinated magnesia powder every 12 hours) during 12 weeks.

Group (C) Agave inulin plus Placebo of Metformin: 10 individuals received inulin in a dosis of 10 mg every 24 hrs (5 mg every 12 hours) plus homologate placebo of metformin (calcinated magnesia) in a dosis of 500 mg per day (with the first bite of the second meal) during 12 weeks.

Group (D) Placebo of Agave inulin plus Placebo of Metformin: homologate placebo of Inulin (calcinated magnesia powder) in a dosis of 10 mg every 24 hrs (5 mg every 12 hours) plus homologate placebo of metformin (calcinated magnesia capsules) in a dosis of 500 mg per day (with the first bite of the second meal) during 12 weeks.

The clinical findings and laboratory test included a metabolic profile and biosafety, which was determined at baseline and at 12 weeks.

Waist, body weight, body fat, body mass index (BMI) and blood pressure were determined at baseline, follow up and final visit, likewise, a blood sample was obtained, centrifuged and stored at -80° degrees Celsius to be analyzed after within 30 days. The investigators assessed glucose, total cholesterol, c-HDL, c-LDL, triglycerides by enzymatic techniques, and adiponectin and insulin by ELISA. Insulin resistance (IR) was estimated by the homeostasis model assessment (HOMA) with the formula for the HOMA (fasting insulin mcg/L x (fasting glucose (mmol/L)/22.5) Adverse events and adherence to treatment were documented every 4 weeks.

Statistical analysis: Values were expressed as mean and standard deviation. Mann-Whitney U Test, Wilcoxon exact test and Kruskal-Wallis. A statistical significance was set at p<0.05.

Conditions

Metabolic Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Agave inulin + Metformin

5 g of Agave inulin powder every 12 hrs + 500 mg tablet of metformin every 24 hrs

Group Type: EXPERIMENTAL

Metformin

Intervention Type: DRUG

Metformin in tablet presentation of 500 mg

Agave inulin

Intervention Type: DIETARY_SUPPLEMENT

Inulin in powder obtained from agave plant, it was given to each patient a full 10 mg container.

Metformin + Placebo of agave inulin

500 mg tablet of metformin every 24 hrs + 5 g every 12 hrs of calcinated magnesia powder

Group Type: ACTIVE_COMPARATOR

Metformin

Intervention Type: DRUG

Metformin in tablet presentation of 500 mg

Placebo of agave inulin

Intervention Type: OTHER

Calcinated magnesia powder

Agave Inulin+Placebo of Metformin

5 g of agave inulin powder every 12 hrs + 500 mg tablet of calcinated magnesia as metformin placebo every 24 hrs

Group Type: ACTIVE_COMPARATOR

Agave inulin

Intervention Type: DIETARY_SUPPLEMENT

Inulin in powder obtained from agave plant, it was given to each patient a full 10 mg container.

Metformin placebo

Intervention Type: OTHER

Calcinated magnesia tablet

Placebo of Inulin + Placebo of Metformin

5 g of calcinated magnesia powder every 12 hrs + 500 mg tablet of calcinated magnesia every 24 hrs

Group Type: PLACEBO_COMPARATOR

Placebo of agave inulin

Intervention Type: OTHER

Calcinated magnesia powder

Metformin placebo

Intervention Type: OTHER

Calcinated magnesia tablet

Interventions

Metformin

Metformin in tablet presentation of 500 mg

Intervention Type: DRUG

Agave inulin

Inulin in powder obtained from agave plant, it was given to each patient a full 10 mg container.

Intervention Type: DIETARY_SUPPLEMENT

Placebo of agave inulin

Calcinated magnesia powder

Intervention Type: OTHER

Metformin placebo

Calcinated magnesia tablet

Intervention Type: OTHER

Other Intervention Names

GLUCOPHAGE

Eligibility Criteria

Inclusion Criteria

• Diagnosis of metabolic syndrome by IDF criteria

• a person to be defined as having the metabolic syndrome they must have: Central obesity (defined as waist circumference* with ethnicity specific values) ≥80 cm in females and ≥90 cm in males; and plus any two of the following four factors:
• Raised triglycerides ≥ 150 mg/dL (1.7 mmol/L) or specific treatment for this lipid abnormality Reduced HDL cholesterol
• < 40 mg/dL (1.03 mmol/L) in males < 50 mg/dL (1.29 mmol/L) in females or specific treatment for this lipid abnormality
• Raised blood pressure systolic BP ≥ 130 or diastolic BP ≥ 85 mm Hg or treatment of previously diagnosed hypertension
• Raised fasting plasma glucose (FPG) ≥ 100 mg/dL (5.6 mmol/L), or previously diagnosed type 2 diabetes
• Age ranging from 40 to 80 years old
• Male patients
• Informed written consent

Exclusion Criteria

• Kidney disease
• Hepatic disease
• Thyroid disease
• Diabetes mellitus
• Ischemic heart disease
• Drug consumption
• Alcohol consumption of more than 2 ounces daily
• Consumption of drugs that intervene with lipid or glucose metabolism 2 months before
• Blood pressure >160/100 mmHg.
• Lack of adherence to treatment (adherence <80%)

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Centro Universitario de Ciencias de la Salud, Mexico

OTHER

Sponsor Role: lead

Responsible Party

Fernando Grover Paez

Fernando Grover-Paez, PhD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Fernando Grover, PhD

Role: PRINCIPAL_INVESTIGATOR

Institute of Experimental and Clinical Therapeutics (INTEC), CUCS, University of Guadalajara

Locations

Universidad de Guadalajara

Guadalajara, Jalisco, México, Mexico

Countries

Mexico

Other Identifiers

CUCS-INTEC-MV-HBP-002

Identifier Type: -

Identifier Source: org_study_id