Metformin & Inflammation in Pre-diabetic Children

July 15, 2011 updated by: Coordinación de Investigación en Salud, Mexico

Metformin Decreases Plasma Resistin Concentrations in Pediatric Patients With Impaired Glucose Tolerance: A Placebo-controlled Randomized Clinical Trial

Hypothesis. To determine the effect of metformin on the concentrations of resistin and other insulin resistance or inflammatory markers (C-reactive protein, cytokines, body weight, HbA1c, among others) in minors with glucose intolerance.

Children with glucose intolerance are given either metformin or placebo for 12 consecutive weeks.

High sensitivity C-reactive protein, TNF-alpha, IL-6, IL1-beta, resistin, leptin, adiponectin, glucose, insulin, HbA1c, lipid profile and transaminases are measured at the beginning and at the end of the period. Statistical analysis: t Student test; Friedman and Kruskal Wallis test are used. Variables are adjusted for: sex, age, baseline BMI and percentage weight change.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Experimental, double-blind, randomized, prospective, placebo-controlled study. Patients aged 4-17 years old are selected from the endocrine outpatient clinic of the Hospital de Pediatria del CMN "Siglo XXI", and both patients and parents sign informed consent. They are scheduled for a fasting oral glucose tolerance test (OGTT) with 1.75 mg/kg of oral glucose. A blood sample is taken from antecubital vein at baseline and 120 minutes.

A high carbohydrate diet is indicated for 3 days prior to the test. All patients diagnosed with glucose intolerance are invited to participate. All followed an aerobic program of 30 to 45 minutes every day, an isocaloric diet from the moment of inclusion throughout the study period, in order to decrease the effect of nutrition modification in the metabolic and vascular parameters. A complete medical history is taken, recording family background of diabetes plus blood pressure, heart rate and Tanner stage13. Age, body weight, height, waist circumference are measured and recorded in percentile according to age and gender, and the body mass index is calculated (kg/m2), and recorded in percentile according to reference values of the Center for the Disease Control, Atlanta, GA14. Subjects are randomized for metformin or placebo. Both metformin and placebo are placed in capsules with gelatin to blind their aspect. Treatments are administered during 3 months. Children are evaluated monthly, measuring transaminases, glucose, creatinine, and uric acid. Measurements of C reactive protein, cytokines, adipokines, insulin concentrations, HbA1c levels and lipid profile are made at the beginning and end of the study. Insulin resistance was assayed by HOMA-IR index. Beta cell function is determined by using HOMA-β. These are complemented with an evaluation of diet, physical activity, and physical examination.

Treatment assignment: Two groups are formed, randomly assigned using a table of random numbers previously designed with the Epistat statistic package (Round Rock, Texas). When the screening finished, every child receives a consecutive number. This number corresponds to an envelope with a card identifying his/her medication flasks, containing 60 tablets of 850 mg or placebo. The content of the capsules is not identified, so both the physician and the patient are blinded. A blinded member of the study prepared the flasks and labeled them.

Participants take the capsules twice daily, at breakfast and dinner. They are instructed to take medication with meals in order to decrease the possibility of adverse effects (nausea, meteorism, diarrhea), which are checked during every visit. Hepatic function is monitored during the study.

FPG, total cholesterol, HDL-cholesterol, triglycerides, liver function tests and creatinine are measured using the Synchron CX analyzer (Beckman Systems, Fullerton CA), according to the standard protocols. The coefficients of variation for cholesterol and HDL-cholesterol are 3.3% and 2.5% respectively. Plasma leptin, adiponectin and insulin concentrations are measured in duplicate by radioinmmunoassay (Linco Research Inc, St Charles, MO). HbA1c is determined in whole blood using ion exchange high performance liquid chromatography (normal range 4-6). Plasma resistin is measured using Human Resistin Elisa Kit (PeproTech, Rock Hill, NJ, USA) read by Multiscan EX, Lab Systems, USA). Plasma IL-6, IL1-b, TNF-α concentrations are determined by ELISA using Quantike HS Human Immunoassay Kits (R&D Systems, Minneapolis, MN, USA), plasma C-reactive protein (hs-CRP) is measured using a highly sensitive human CRP ELISA Kit (Alpha diagnostic international, San Antonio, TX, USA ) according to the manufacturer's instructions and are read by an ELISA reader (Sunrise, Tecan USA, Durham NC,USA).

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
52

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Mexico
    • DF
      • Mexico City, DF, Mexico, 06720
        • Endocrine Outpatient Clinic of the Hospital de Pediatria del CMN "Siglo XXI"

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

4 years to 17 years (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • pediatric patients with glucose intolerance per ADA criteria,
  • free of acute or chronic inflammatory processes 3 months prior to recruitment,
  • 4-17 years of age

Exclusion Criteria:

  • previous personal history of diabetes or demonstrating diabetes in OGTT curve,
  • chronic renal disease or serum creatinine over 1.4 mg/dl (females) or 1.5 (males),
  • active hepatic disease,
  • smoking,
  • primary dislipidemia,
  • heart problems,
  • steroids,
  • chronic metabolic acidosis,
  • receiving anti-hypertensive or hypolipemia or hypoglucemia medications

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: metformin group
this group received 850 mg metformin twice daily, along with recommended diet and exercise
Drug: Metformin
850 mg of metformin twice daily over 12 weeks
Other Names:
  • Diet and physical activity
Placebo Comparator: placebo group
This group received 850 mg of placebo twice daily, along with a recommended regimen of diet and exercise
Drug: placebo
850 mg gel capsules with starch (6.8 calories)as placebo
Other Names:
  • Diet and physical activity

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
presence of inflammation
Time Frame: 1 year
to determine the efficacy of metformin in avoiding deterioration of glucose intolerance to type 2 diabetes, as measured by inflammation through various recognized inflammation markers
1 year

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
presence of type 2 diabetes
Time Frame: 10 years
to determine the efficacy of metformin in avoiding deterioration of glucose intolerance to type 2 diabetes, as measured by inflammation through various recognized inflammation markers
10 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Coordinación de Investigación en Salud, Mexico

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Niels H Wacher, MD, Supervisor Clinical Research

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 1, 2002

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 1, 2003

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 1, 2011

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 13, 2011

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 14, 2011

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 15, 2011

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 18, 2011

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 15, 2011

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2002

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2002-718-0018

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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