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Adjunctive Metformin Therapy in Double Diabetes (AMTIDD)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Benjamin U. Nwosu, University of Massachusetts, Worcester
ClinicalTrials.gov Identifier:
NCT01334125
First received: March 21, 2011
Last updated: March 3, 2016
Last verified: March 2016
  Purpose
The significance of this project is to investigate the effects of adjunctive metformin therapy in children and adolescents with double diabetes. Double diabetes describes a clinical state where an individual possesses features of both type 1 and type 2 diabetes. There is a paucity of data on the role of adjunctive metformin therapy in children and adolescents with double diabetes. To help fill this knowledge gap, the investigators propose a randomized, double-blind, placebo-controlled trial of metformin in double diabetes. Specifically, the investigators will evaluate changes in hemoglobin A1c and anthropometry in patients with a diagnosis of type 1 diabetes who also have features of type 2 diabetes or metabolic syndrome as well as patients with type 2 diabetes who possess diabetes-associated autoantibodies. This will help determine the safety profile, and efficacy of adjunctive metformin therapy in these subjects.

Condition Intervention Phase
Diabetes Mellitus
Drug: Metformin
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Glycemic Control in Children and Adolescents With Double Diabetes: Trial of Optimized Insulin-Metformin Regimen

Resource links provided by NLM:


Further study details as provided by University of Massachusetts, Worcester:

Primary Outcome Measures:
  • Baseline Adjusted Hemoglobin A1c Over Time [ Time Frame: Baseline, 3mo, 6mo, and 9 months ] [ Designated as safety issue: No ]
    Comparison of the baseline-adjusted differences in HbA1c between the metformin and placebo groups during the trial. Hemoglobin A1c is a marker of glycemic control. The reported values represented means adjusted for baseline values, age, gender, and BMI using repeated measures ANOVA (General Linear Model).


Secondary Outcome Measures:
  • Baseline Adjusted Changes in Lipid Profile Over Time [ Time Frame: Baseline, 3mo, 6mo, and 9 months ] [ Designated as safety issue: No ]
    Comparison of the baseline-adjusted differences in total cholesterol/high density cholesterol index over time between the metformin and the placebo groups. The reported values represented means adjusted for baseline values, age, gender, and BMI using repeated measures ANOVA (General Linear Model).

  • Baseline Adjusted Changes in Adiponectin/Leptin Ratio Over Time [ Time Frame: Baseline, 3mo, 6 mo, and 9 months ] [ Designated as safety issue: No ]
    Comparison of the baseline-adjusted differences in adiponectin/leptin ratio over time between the metformin and the placebo groups. The reported values represented mean adjusted for baseline values, age, gender, and BMI using repeated measures ANOVA (General Linear Model).

  • Number of Participants With Minor, Major, and Nocturnal Hypoglycemia [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    Comparison of the occurrence of hypoglycemic event requiring a third party assistance (major hypoglycemia) per subject during the study, and minor hypoglycemia (plasma glucose of <60 mg/dL or no measurement), as well as nocturnal hypoglycemia (plasma glucose of ≤60 mg/dL between 11PM and 6AM).


Enrollment: 28
Study Start Date: February 2011
Study Completion Date: December 2014
Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Metformin
Metformin 1000 mg once daily by mouth for 9 months
Drug: Metformin
Metformin 1000 mg once daily by mouth for 9 months
Other Name: Glucophage
Placebo Comparator: Placebo
2 capsules once daily by mouth for 9 months
Drug: Placebo
2 capsules once daily by mouth for 9 months

Detailed Description:
In this 12-month clinical trial, a 3-month run-in period will precede the interventional phase of the study. All patients will be placed on treat-to-target insulin regimen alone during the run-in phase. At the end of the 3-month run-in period, all participants will continue on treat-to-target insulin regimen, and will then be randomized to either of the 2 arms of the study: an experimental arm, consisting of treat-to-target insulin regimen plus metformin, and a control arm consisting of treat-to-target insulin regimen plus placebo. Both the physicians and patients will be blinded to the oral agents being administered to patients.
  Eligibility

Ages Eligible for Study:   10 Years to 20 Years   (Child, Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

A. General inclusion criteria

  1. Ten to 20 years of age.
  2. Pubertal (Tanner stages 2-5, by examination).
  3. Hemoglobin A1c level of > 8.0% in the 6 months prior to enrollment.
  4. All subjects must have access to a computer.

B. Specific inclusion criteria: [Subjects could have either #1, or #2].

  1. Subjects with clinical and biochemical features of T2DM of > 6mo duration who also have positive T1DM antibodies

    • Clinical features: acanthosis nigricans, BMI >85%
    • Biochemical: evidence of insulin resistance at diagnosis
    • fasting insulin >27 uIU/mL(normal range 6-27) at a fasting blood glucose of ≥ 126 mg/dL, or
    • fasting c-peptide level of > 7.1 ng/mL (normal range 0.9 - 7.1), or
    • Homeostasis model of insulin resistance of >3.16
  2. Patients with T1DM of > one yr duration with BMI >85%

    • Presentation with ketoacidosis at diagnosis
    • C-peptide <0.9 ng/mL (normal range 0.9 - 7.1),or (insulin < 6 uIU/mL) (NR 6-27) at diagnosis (when blood glucose is ≥ 126 mg/dL)
    • Can be antibody positive or negative
    • Increased insulin requirement (>2 Units/kg/day)

Exclusion Criteria:

  1. Subjects on weight altering medications, such as orlistat.
  2. Subjects with eating disorder
  3. Subjects on medications other than insulin and or metformin that may affect blood glucose level.
  4. Subjects with abnormal hepatic function tests.
  5. Subjects with nephropathy, defined in this case as an overnight albumin excretion rate of >200 mcg/min using a first morning urine sample collection.
  6. Subjects with recurrent diabetes ketoacidosis (more than 2 episodes in the past 12 months), or recurrent severe hypoglycemia (more than 2 episodes of hypoglycemia with altered level of consciousness, requiring assistance to treat in the past year).
  7. Pregnant, breast-feeding or the intention of becoming pregnant or not using adequate contraceptive measures.
  8. Known or suspected allergy to metformin.
  9. The receipt of any investigational drug within 6 months prior to this trial.
  10. Active malignant neoplasms.
  11. No access to a computer.
  12. Subjects currently taking metformin for clinical purposes are not eligible to be enrolled in this study.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01334125

Locations
United States, Massachusetts
UmassMemorial Medical Center
Worcester, Massachusetts, United States, 01655
Sponsors and Collaborators
University of Massachusetts, Worcester
Investigators
Principal Investigator: Benjamin U Nwosu, MD University of Massachusetts, Worcester
  More Information

Publications:
Responsible Party: Benjamin U. Nwosu, Study Principle Investigator, University of Massachusetts, Worcester
ClinicalTrials.gov Identifier: NCT01334125     History of Changes
Other Study ID Numbers: 13938 
Study First Received: March 21, 2011
Results First Received: January 27, 2016
Last Updated: March 3, 2016
Health Authority: United States: Institutional Review Board

Keywords provided by University of Massachusetts, Worcester:
Double Diabetes
Type 1 diabetes
Type 2 diabetes
Obesity
Acanthosis nigricans
Diabetes associated autoantibodies

Additional relevant MeSH terms:
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Metformin
Hypoglycemic Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on December 02, 2016