Metformin Therapy for Overweight Adolescents With Type 1 Diabetes

February 28, 2020 updated by: Jaeb Center for Health Research

A Randomized Trial of Metformin as Adjunct Therapy for Overweight Adolescents With Type 1 Diabetes

The objective of the proposed research is to evaluate the efficacy and safety of the use of metformin in addition to standard insulin therapy in overweight and obese children and adolescents, age 12-<20 years, with type 1 diabetes for at least 1 year. Secondary objectives are to assess the effect of metformin on C-peptide levels, a measure of how much insulin is still being produced by the beta cells of the pancreas, and on vascular dysfunction. In addition, an ancillary study is planned to assess if metformin will improve tissue-specific insulin resistance in type 1 diabetes using a hyperinsulinemic euglycemic clamp.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

164

Phase

  • 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

  • United States
    • Florida
      • Tampa, Florida, United States, 33647
        • Jaeb Center for Health Research

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

12 years to 19 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Clinical diagnosis of presumed autoimmune type 1 diabetes (T1D) as indicated by age of diagnosis <10 years or documented positive diabetes-related autoantibodies.

    a. Note: For randomization, presence of at least one of the diabetes-related autoantibodies [Insulin autoantibodies (IAA) at diagnosis prior to initiation of insulin, Islet cell antibodies (ICA), Anti-GAD (GAD65), Anti-IA2 (IA2), Zinc Transporter 8 (ZnT8)] must be documented either from medical records or new laboratory measurement (IAA and ICA not measured by central lab) sent to central lab for participants who were ≥10 years old at diagnosis.

  2. Age: 12 to <20 years.
  3. Duration of type 1 diabetes: ≥1 years.
  4. Current insulin regimen involves either use of an insulin pump or multiple daily injections of insulin (at least 3 shots per day) for the last three months, with no plans to switch the modality of insulin administration during the next 6 months (e.g., injection user switching to a pump, pump user switching to injections).
  5. Hemoglobin A1c: 7.5% - <10.0% from point of care measurement or local lab on day of screening visit or within 1 month prior.
  6. BMI: ≥85th percentile adjusted for age and sex .
  7. Total daily dose of insulin: ≥0.8 units per kg per day.
  8. Average of ≥3 Self-Monitoring Blood Glucose (SMBG) tests per day prior to initiating study and from download of study-provided blood glucose meter following screening visit.
  9. Available for at least 6 months of follow-up, has home phone (or access to phone), and willing to be contacted by clinical site staff.
  10. Expected to comply with protocol in investigator's judgment.

Exclusion Criteria:

  1. Use of non-insulin medications for blood glucose control within prior 6 months or planning to use within next 6 months (other than study drug).
  2. Use of medications for weight reduction (such as: Belviq (lorcaserin), Qsymia (Phentermine + topiramate), Orlistat (xenical)) within the prior 6 months or planning to use within next 6 months.
  3. Use of a medication such as stimulants, psychotropic agents and oral/inhaled glucocorticoids that could affect weight gain or glycemic control of T1D or planning to use within the next 6 months.
  4. Any condition that in the judgment of the investigator will adversely affect the completion of the protocol.

  5. Females: pregnant, lactating, or intending to become pregnant within the next 34 weeks

    • A negative urine pregnancy test will be required for all females An effective contraceptive method or abstinence will be required for all females who have experienced menarche
    • Requirements regarding pregnancy testing prior to enrollment and monitoring for pregnancy over the course of the study may be further defined by each individual Institutional Review Board (IRB)
  6. Clinical diagnosis of celiac disease that is in poor control as defined by most recent tissue transglutaminase (tTG) that is in the abnormal range.
  7. History of ≥1 diabetic ketoacidosis events in the past 3 months.
  8. History of ≥1 severe hypoglycemic events (cognitive impairment that required assistance to treat) in the past 3 months.
  9. History of anemia or vitamin B12 deficiency in the past 2 years.
  10. Participation in an intervention study in the past 3 months.

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: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Metformin
Metformin 2000 mg per day
Drug: Metformin (glucophage)
The strength of each tablet will be 500 mg. Participants will build up to a daily dose over four weeks by taking one tablet per day for 7 days, one tablet twice daily for 7 days, one tablet in morning and 2 tablets at night for 7 days, and then 2 tablets in the morning and 2 tablets at night, daily throughout the remainder of the study treatment period.
Placebo Comparator: Oral Placebo

A central pharmacy will compound a placebo to match the metformin tablets.

The placebo product will contain the following components:

  • Micosolle™, silica based excipient
  • Silicified Micro Crystalline Cellulose, National Formulary
  • Safflower Oil, United States Pharmacopeia
  • K-30 Povidone Powder
  • Magnesium Stearate, National Formulary (Vegetable source)
  • Fumed Silica, National Formulary
Other: oral placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Hemoglobin A1c From Baseline to 26 Weeks, Adjusted for Baseline Hemoglobin A1c.
Time Frame: 0-26 weeks
Hemoglobin A1c is a measure of glycemic control over approximately the past 3 months
0-26 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Total Daily Dose of Insulin (TDI) Per kg
Time Frame: 0-26 weeks
0-26 weeks
Change in Body Mass Index (BMI)
Time Frame: 0-26 weeks
0-26 weeks
Change in Waist Circumference
Time Frame: 0-26 weeks
0-26 weeks
Change in Body Composition
Time Frame: 0-26 weeks
Change in percent body fat
0-26 weeks
Change in Serum Lipids
Time Frame: 0-26 weeks
0-26 weeks
Change in Blood Pressure
Time Frame: 0-26 weeks
0-26 weeks

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Liver Enzymes and Serum Creatinine
Time Frame: 0-26 weeks
0-26 weeks
Frequency of Severe Hypoglycemia
Time Frame: 26 weeks
26 weeks
Frequency of Diabetic Ketoacidosis
Time Frame: 26 weeks
26 weeks
Frequency of Gastrointestinal Side-effects Including Stomach Discomfort, Diarrhea, Nausea/Vomiting, Indigestion, Flatulence.
Time Frame: 26 weeks
26 weeks
Frequency of Lactic Acidosis
Time Frame: 26 weeks
26 weeks
Change in Adipocytokines
Time Frame: 0-26 weeks
0-26 weeks
Change in Androgen Levels in Females
Time Frame: 0-26 weeks
0-26 weeks
Change in C-peptide
Time Frame: 0-26-weeks
Measured with mixed meal tolerance test among participants with evidence of residual C-peptide on a non-fasting C-peptide at screening
0-26-weeks
Change in Vascular Dysfunction
Time Frame: 0-26 weeks
0-26 weeks

Collaborators and Investigators

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

Sponsor

Jaeb Center for Health Research

Collaborators

Juvenile Diabetes Research Foundation

Investigators

  • Principal Investigator: Kellee Miller, MPH, Jaeb Center for Health Research
  • Study Chair: Ingrid Libman, MD, PhD, Childrens Hospital of University of Pittsburgh Medical Center
  • Study Chair: Kristen Nadeau, MD, University of Colorado Denver/Childrens Hospital Colorado

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

September 1, 2013

Primary Completion (Actual)

September 1, 2014

Study Completion (Actual)

December 1, 2014

Study Registration Dates

First Submitted

June 13, 2013

First Submitted That Met QC Criteria

June 17, 2013

First Posted (Estimate)

June 20, 2013

Study Record Updates

Last Update Posted (Actual)

March 3, 2020

Last Update Submitted That Met QC Criteria

February 28, 2020

Last Verified

February 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • T1DX-17-2013-506
  • 17-2013-506 (Other Grant/Funding Number: JDRF)

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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