Effect of Metformin in Children With Type 1 Diabetes

May 6, 2021 updated by: Nancy Samir Elbarbary, Ain Shams University

Effect of Metformin on Circulating Neuregulin-4 in Children With Type 1 Diabetes

Cardiovascular disease is the leading cause of mortality in type 1 diabetes mellitus (T1DM). Vascular dysfunction is an early and critical event in the development of cardiovascular disease. Children with T1DM have vascular dysfunction therefore early interventions to improve vascular health are essential to reduce cardiovascular mortality in T1DM. Metformin is an insulin sensitising agent which is known to improve vascular health outcomes in type 2 diabetes mellitus (T2DM) and other individuals with insulin resistance. It has been used safely in children and adolescents with T2DM for over 10 years. This study aims to assess the effect of metformin on vascular health in children with T1DM.

This is the first study to study effect of metformin on circulating neuregulin-4 levels as a marker for subclinical atherosclerosis.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Type 1 diabetes mellitus (T1DM) is an autoimmune disease characterized by T-cell mediated destruction of the pancreatic b-cells, resulting in insulin deficiency and elevated blood glucose levels.

The increasing incidence of type 1 diabetes mellitus in many countries challenges health systems because the disease is presently incurable with no known method of prevention. Around 490,100 children live with the disease worldwide, with incidence estimated to be increasing in children under 15 years by 2.8% per year .This trend is particularly worrying because type 1 diabetes increases mortality and morbidity population-wide.

Vascular co-morbid diseases include retinopathy, which may cause reduced vision and blindness, and nephropathy, which may result in renal failure and require dialysis or kidney transplantation. This is in addition to hypertension, which is linked to peripheral, cardio- and cerebrovascular disease, the end points of which are limb amputations, cardiac failure, stroke and sudden death. As vascular complications curtail both life expectancy and quality of life development at younger ages when people are typically establishing Type 1 diabetes mellitus (T1DM) is an autoimmune disease characterized by T-cell mediated destruction of the pancreatic b-cells, resulting in insulin deficiency and elevated blood glucose levels.

The increasing incidence of type 1 diabetes mellitus in many countries challenges health systems because the disease is presently incurable with no known method of prevention . Around 490,100 children live with the disease worldwide, with incidence estimated to be increasing in children under 15 years by 2.8% per year .This trend is particularly worrying because type 1 diabetes increases mortality and morbidity population-wide.

Vascular co-morbid diseases include retinopathy, which may cause reduced vision and blindness, and nephropathy, which may result in renal failure and require dialysis or kidney transplantation. This is in addition to hypertension, which is linked to peripheral, cardio- and cerebrovascular disease, the end points of which are limb amputations, cardiac failure, stroke and sudden death. As vascular complications curtail both life expectancy and quality of life development at younger ages when people are typically establishing careers and families is particularly detrimental .

Neuregulin 4 (Nrg4), a recently identified adipokine, has been found in multiple organs, in particular brown adipose tissue (BAT), and belongs to the epidermal growth factor (EGF) family of extracellular ligands. Overexpression of Nrg4 can reduce chronic inflammation through inhibiting the gene expression of macrophage marker monocyte chemotactic protein 1 (Mcp1) and enhancing the expression of M2 macrophage marker gene Cd163, demonstrating that Nrg4 may possess anti-inflammatory and anti-atherogenic properties. Lower Nrg4 levels have been reported to be associated with the percentage of body fat mass, liver fat content, obesity, IR, impaired glucose tolerance (IGT), and type 2 diabetes mellitus (T2DM) .

Moreover, serum Nrg4 levels have been reported to be inversely associated with subclinical cardiovascular disease (CVD) in obese adults.

Recent studies reveal that neuregulin.4 may be closely associated with non-alcoholic fatty liver disease (NAFLD) and metabolic syndrome (MetS). Many lines of evidence indicate that inflammation is closely associated with atherosclerosis and plays a crucial role in the development of CVD.

Biguanides sensitize body cells to insulin, which may cause a reduction of atherogenic lipid fractions in patients with type 2 diabetes.

Study Type

Interventional

Enrollment (Actual)

80

Phase

  • 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

  • Egypt
      • Cairo, Egypt, 11361
        • Nancy Elbarbary

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

Ages Eligible for Study

7 years to 18 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients with type 1 diabetes mellitus (5 years duration at least) and with micro-vascular complications.
  • Patients on regular visits to clinic.
  • Patients on regular insulin therapy.

Exclusion Criteria:

  • Any clinical evidence of infection, hematological diseases, tumors, liver dysfunction, urinary tract disorders, connective tissue disease, or other autoimmune diseases.

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: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Receiving metformin
Active group receiving metformin with basal /bolus insulin
Drug: metformin
Oral hypoglycemic drug metformin
Other Names:
  • Glucophage
Drug: Basal/bolus insulin
Basal/bolus insulin
Placebo Comparator: Placebo
Control group receiving Placebo with basal/bolus insulin
Drug: Basal/bolus insulin
Basal/bolus insulin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Glycemic control(HbA1c%)
Time Frame: up to 24 weeks
Effect of metformin supplementation on Glycemic control(HbA1c%)
up to 24 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
circulating neuregulin-4 level
Time Frame: up to 24 weeks
Effect of metformin supplementation on level of circulating neuregulin-4
up to 24 weeks

Collaborators and Investigators

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

Sponsor

Ain Shams University

Investigators

  • Principal Investigator: Nancy S Elbarbary, MD.PhD, Ain Shams University

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 (Actual)

February 10, 2018

Primary Completion (Actual)

January 1, 2021

Study Completion (Actual)

January 29, 2021

Study Registration Dates

First Submitted

April 30, 2021

First Submitted That Met QC Criteria

May 6, 2021

First Posted (Actual)

May 10, 2021

Study Record Updates

Last Update Posted (Actual)

May 10, 2021

Last Update Submitted That Met QC Criteria

May 6, 2021

Last Verified

May 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Ain shams Pediatrics 2102018

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

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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