Metformin Therapy for Overweight Adolescents With Type 1 Diabetes

Type 1 Diabetes Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01881828
• Other study ID #: T1DX-17-2013-506
• Secondary ID: 17-2013-506
• Status: Completed
• Phase: Phase 3
• Start date: September 2013
• Est. completion date: December 2014

Study information

• Verified date: February 2020
• Source: Jaeb Center for Health Research
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 164
• Est. completion date: December 2014
• Est. primary completion date: September 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 19 Years

Eligibility

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.

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Overweight
• Type 1 Diabetes

Intervention

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.

Other:
• oral placebo

Locations

Country	Name	City	State
United States	Jaeb Center for Health Research	Tampa	Florida

Sponsors (2)

Lead Sponsor	Collaborator
Jaeb Center for Health Research	Juvenile Diabetes Research Foundation

Country where clinical trial is conducted

United States, 

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* Note: There are 48 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in Liver Enzymes and Serum Creatinine		0-26 weeks
Other	Frequency of Severe Hypoglycemia		26 weeks
Other	Frequency of Diabetic Ketoacidosis		26 weeks
Other	Frequency of Gastrointestinal Side-effects Including Stomach Discomfort, Diarrhea, Nausea/Vomiting, Indigestion, Flatulence.		26 weeks
Other	Frequency of Lactic Acidosis		26 weeks
Other	Change in Adipocytokines		0-26 weeks
Other	Change in Androgen Levels in Females		0-26 weeks
Other	Change in C-peptide	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
Other	Change in Vascular Dysfunction		0-26 weeks
Primary	Change in Hemoglobin A1c From Baseline to 26 Weeks, Adjusted for Baseline Hemoglobin A1c.	Hemoglobin A1c is a measure of glycemic control over approximately the past 3 months	0-26 weeks
Secondary	Change in Total Daily Dose of Insulin (TDI) Per kg		0-26 weeks
Secondary	Change in Body Mass Index (BMI)		0-26 weeks
Secondary	Change in Waist Circumference		0-26 weeks
Secondary	Change in Body Composition	Change in percent body fat	0-26 weeks
Secondary	Change in Serum Lipids		0-26 weeks
Secondary	Change in Blood Pressure		0-26 weeks