Adjunctive Metformin Therapy in Double Diabetes | RxWiki

Adjunctive Metformin Therapy in Double Diabetes

Overview[ - collapse ][ - ]

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	Diabetes Mellitus
Intervention	Drug: Metformin Drug: Placebo
Phase	Phase 3
Sponsor	University of Massachusetts, Worcester
Responsible Party	University of Massachusetts, Worcester
ClinicalTrials.gov Identifier	NCT01334125
First Received	March 21, 2011
Last Updated	November 22, 2013
Last verified	November 2013

Tracking Information[ + expand ][ + ]

First Received Date	March 21, 2011
Last Updated Date	November 22, 2013
Start Date	February 2011
Estimated Primary Completion Date	December 2014
Current Primary Outcome Measures	The proportion of subjects reaching HbA1c levels <8% at 12 months. [Time Frame: Every 3 months for 12 months] [Designated as safety issue: Yes]
Current Secondary Outcome Measures	Changes in anthropometry [Time Frame: Every 3 months for 12 months] [Designated as safety issue: Yes] Changes in lipid profile [Time Frame: Every 3 months for 12 months] [Designated as safety issue: Yes] Changes in adipocytokines [Time Frame: Every 3 months for 12 months] [Designated as safety issue: No] Changes in total daily insulin requirement [Time Frame: Every 3 months for 12 months] [Designated as safety issue: Yes] Assessment of the rates of hypoglycemia (blood glucose level ≤60 mg/dL) or hypoglycemic event requiring a third party assistance per subject per week. [Time Frame: Every week for 12 months] [Designated as safety issue: Yes]

Descriptive Information[ + expand ][ + ]

Brief Title	Adjunctive Metformin Therapy in Double Diabetes
Official Title	Glycemic Control in Children and Adolescents With Double Diabetes: Trial of Optimized Insulin-Metformin Regimen
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.
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.
Study Type	Interventional
Study Phase	Phase 3
Study Design	Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Condition	Diabetes Mellitus
Intervention	Drug: Metformin Metformin 1000 mg once daily by mouth for 9 months Other Names: GlucophageDrug: Placebo 2 capsules once daily by mouth for 9 months Other Names: Placebo
Study Arm (s)	Experimental: Metformin Metformin 1000 mg once daily by mouth for 9 months Placebo Comparator: Placebo 2 capsules once daily by mouth for 9 months

Recruitment Information[ + expand ][ + ]

Recruitment Status	Recruiting
Estimated Enrollment	80
Estimated Completion Date	December 2014
Estimated Primary Completion Date	December 2014
Eligibility 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.
Gender	Both
Ages	10 Years
Accepts Healthy Volunteers	No
Contacts	Contact: Benjamin U Nwosu, MD 508-334-7872 benjamin.nwosu@umassmemorial.org
Location Countries	United States

Administrative Information[ + expand ][ + ]

NCT Number	NCT01334125
Other Study ID Numbers	13938
Has Data Monitoring Committee	Yes
Information Provided By	University of Massachusetts, Worcester
Study Sponsor	University of Massachusetts, Worcester
Collaborators	Not Provided
Investigators	Principal Investigator: Benjamin U Nwosu, MD University of Massachusetts, Worcester
Verification Date	November 2013

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