Clinical trial NCT01881828: Metformin Therapy for Overweight Adolescents With Type 1 Diabetes
Official title: A Randomized Trial of Metformin as Adjunct Therapy for Overweight Adolescents With Type 1 Diabetes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Type 1 Diabetes
Lead sponsor: Jaeb Center for Health Research
Sponsor class: OTHER
Collaborators: name: Juvenile Diabetes Research Foundation
First posted: 2013-06-20
Enrollment: 164
Sex: ALL
Minimum age (years): 12
Maximum age (years): 19
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Change in Hemoglobin A1c From Baseline to 26 Weeks, Adjusted for Baseline Hemoglobin A1c.
timeFrame: 0-26 weeks
Secondary outcomes:
measure: Change in Total Daily Dose of Insulin (TDI) Per kg
timeFrame: 0-26 weeks
measure: Change in Body Mass Index (BMI)
timeFrame: 0-26 weeks
measure: Change in Waist Circumference
timeFrame: 0-26 weeks
measure: Change in Body Composition
timeFrame: 0-26 weeks
measure: Change in Serum Lipids
timeFrame: 0-26 weeks
measure: Change in Blood Pressure
timeFrame: 0-26 weeks
Other outcomes:
measure: Change in Liver Enzymes and Serum Creatinine
timeFrame: 0-26 weeks
measure: Frequency of Severe Hypoglycemia
timeFrame: 26 weeks
measure: Frequency of Diabetic Ketoacidosis
timeFrame: 26 weeks
measure: Frequency of Gastrointestinal Side-effects Including Stomach Discomfort, Diarrhea, Nausea/Vomiting, Indigestion, Flatulence.
timeFrame: 26 weeks
measure: Frequency of Lactic Acidosis
timeFrame: 26 weeks
measure: Change in Adipocytokines
timeFrame: 0-26 weeks
measure: Change in Androgen Levels in Females
timeFrame: 0-26 weeks
measure: Change in C-peptide
timeFrame: 0-26-weeks
measure: Change in Vascular Dysfunction
timeFrame: 0-26 weeks
Locations:
city: Tampa
country: United States
facility: Jaeb Center for Health Research
state: Florida
Study officials:
affiliation: Jaeb Center for Health Research
name: Kellee Miller, MPH
role: PRINCIPAL_INVESTIGATOR
affiliation: Childrens Hospital of University of Pittsburgh Medical Center
name: Ingrid Libman, MD, PhD
role: STUDY_CHAIR
affiliation: University of Colorado Denver/Childrens Hospital Colorado
name: Kristen Nadeau, MD
role: STUDY_CHAIR
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