NCT01334125

Brief Summary

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
28

participants targeted

Target at below P25 for phase_3 diabetes-mellitus

Timeline
Completed

Started Feb 2011

Typical duration for phase_3 diabetes-mellitus

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

February 1, 2011

Completed
2 months until next milestone

First Submitted

Initial submission to the registry

March 21, 2011

Completed
22 days until next milestone

First Posted

Study publicly available on registry

April 12, 2011

Completed
3.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2014

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2014

Completed
1.3 years until next milestone

Results Posted

Study results publicly available

March 4, 2016

Completed
Last Updated

March 4, 2016

Status Verified

March 1, 2016

Enrollment Period

3.8 years

First QC Date

March 21, 2011

Results QC Date

January 27, 2016

Last Update Submit

March 3, 2016

Conditions

Diabetes Mellitus

Keywords

Double DiabetesType 1 diabetesType 2 diabetesObesityAcanthosis nigricansDiabetes associated autoantibodies

Outcome Measures

Primary Outcomes (1)

  • Baseline Adjusted Hemoglobin A1c Over Time

    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).

    Baseline, 3mo, 6mo, and 9 months

Secondary Outcomes (3)

  • Baseline Adjusted Changes in Lipid Profile Over Time

    Baseline, 3mo, 6mo, and 9 months

  • Baseline Adjusted Changes in Adiponectin/Leptin Ratio Over Time

    Baseline, 3mo, 6 mo, and 9 months

  • Number of Participants With Minor, Major, and Nocturnal Hypoglycemia

    12 months

Study Arms (2)

Metformin

EXPERIMENTAL

Metformin 1000 mg once daily by mouth for 9 months

Drug: Metformin

Placebo

PLACEBO COMPARATOR

2 capsules once daily by mouth for 9 months

Drug: Placebo

Interventions

MetforminDRUG

Metformin 1000 mg once daily by mouth for 9 months

Also known as: Glucophage
Metformin
PlaceboDRUG

2 capsules once daily by mouth for 9 months

Placebo

Eligibility Criteria

Age10 Years - 20 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64)

You may qualify if:

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

You may not qualify if:

  • Subjects on weight altering medications, such as orlistat.
  • Subjects with eating disorder
  • Subjects on medications other than insulin and or metformin that may affect blood glucose level.
  • Subjects with abnormal hepatic function tests.
  • Subjects with nephropathy, defined in this case as an overnight albumin excretion rate of \>200 mcg/min using a first morning urine sample collection.
  • 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).
  • Pregnant, breast-feeding or the intention of becoming pregnant or not using adequate contraceptive measures.
  • Known or suspected allergy to metformin.
  • The receipt of any investigational drug within 6 months prior to this trial.
  • Active malignant neoplasms.
  • No access to a computer.
  • Subjects currently taking metformin for clinical purposes are not eligible to be enrolled in this study.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

UmassMemorial Medical Center

Worcester, Massachusetts, 01655, United States

Location

Related Publications (1)

  • Nwosu BU, Maranda L, Cullen K, Greenman L, Fleshman J, McShea N, Barton BA, Lee MM. A Randomized, Double-Blind, Placebo-Controlled Trial of Adjunctive Metformin Therapy in Overweight/Obese Youth with Type 1 Diabetes. PLoS One. 2015 Sep 14;10(9):e0137525. doi: 10.1371/journal.pone.0137525. eCollection 2015.

    PMID: 26367281RESULT

MeSH Terms

Conditions

Diabetes MellitusDiabetes Mellitus, Type 1Diabetes Mellitus, Type 2ObesityAcanthosis Nigricans

Interventions

Metformin

Condition Hierarchy (Ancestors)

Glucose Metabolism DisordersMetabolic DiseasesNutritional and Metabolic DiseasesEndocrine System DiseasesAutoimmune DiseasesImmune System DiseasesOverweightOvernutritionNutrition DisordersBody WeightSigns and SymptomsPathological Conditions, Signs and SymptomsMelanosisHyperpigmentationPigmentation DisordersSkin DiseasesSkin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

BiguanidesGuanidinesAmidinesOrganic Chemicals

Limitations and Caveats

The trial was stopped before reaching enrollment target because most youth were reluctant to commit to this long-term study.

Results Point of Contact

Title
Benjamin U. Nwosu, MD
Organization
University of Massachusetts Medical School
Benjamin.Nwosu@umassmemorial.org
5083347872

Study Officials

  • Benjamin U Nwosu, MD

    University of Massachusetts, Worcester

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Study Principle Investigator

Study Record Dates

First Submitted

March 21, 2011

First Posted

April 12, 2011

Study Start

February 1, 2011

Primary Completion

December 1, 2014

Study Completion

December 1, 2014

Last Updated

March 4, 2016

Results First Posted

March 4, 2016

Record last verified: 2016-03

Locations

US(1)