Metformin and Transient Hyperglycemia

Study Overview
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Brief Summary
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The purpose of this study is to determine whether metformin is an effective adjunctive treatment for transient hyperglycemia in patients with acute lymphoblastic leukemia (ALL) undergoing induction chemotherapy

Detailed Description
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ALL is the most common childhood cancer, representing one fourth of all cancers diagnosed under the age of 15 years. One of the most common side effects of ALL chemotherapy is transient hyperglycemia. Patients that develop this complication require treatment with insulin via injections to prevent severe medical complications such as dehydration, weight loss, ketoacidosis and life-threatening infections. Although insulin therapy is effective, it adds a lot of physical and psychological burden to patients because multiple daily insulin injections are required to achieve adequate blood glucose control. In this pilot study, investigators aim to examine the effectiveness of metformin as an adjunctive treatment for transient hyperglycemia. Investigators will be comparing two groups of subjects (up to 40 subjects per group). Patients in the treatment group will be prospectively recruited, and they will be treated with metformin in addition to insulin therapy. Investigators will compare the treatment group to a historical control group acquired via chart review. These patients will have been treated with insulin alone. Statistical comparison will be made between the two groups in terms of the length of insulin treatment, the total daily dose of insulin required, number of insulin injections, hemoglobin A1c level (measure of glycemic control over preceding 8- 12 weeks), and fructosamine level (measure of glycemic control over preceding 2-3 weeks). Investigators hypothesize that the use of metformin will result in fewer numbers of insulin injections and fewer days of insulin therapy.

Official Title
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Metformin as an Adjunctive Therapy For Transient Hyperglycemia in Patients With Acute Lymphoblastic Leukemia During Induction Chemotherapy

Conditions
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Acute Lymphoblastic Leukemia, Hyperglycemia, Insulin Resistance, Diabetes Mellitus

Intervention / Treatment
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* Drug: Metformin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ALL patients on induction chemotherapy who develop transient hyperglycemia(definition of transient hyperglycemia: random blood glucose > 200 mg/dL x 2) Adequate renal function (serum Cr < 1.5 mg/dL in males, < 1.2 mg/dL in females) Adequate hepatic function (AST < 5x upper limit of normal) Exclusion Criteria: Patients with known diagnosis of diabetes or those that are already on oral hypoglycemic agents or insulin Allergy to metformin or any component of the formulation Patients with pancreatitis (lipase level > 300 Units/L) Patients with active infection (positive blood culture within 48 hours of study registration) Patients with hemodynamic instability (PICU status, need for vasopressors within 48 hours of study entry) Elevated hemoglobin A1c (greater than 6.0%)

Ages Eligible for Study
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Minimum Age: 10 Years
Maximum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Metformin and insulin therapy<br>Up to 30-40 patients will be in the prospectively recruited treatment group, which will receive both metformin and insulin therapy for transient hyperglycemia | Drug: Metformin<br>* All subjects will be started on metformin 500 mg orally twice daily. The dose will be increased by 500 mg weekly as tolerated until subjects' blood glucoses are well controlled or until the patient reaches metformin 1000 mg PO BID.<br>* Other names: Glucophage, Metformin HCl;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Length of Insulin Therapy (Days) |  | During the 30 days of induction chemotherapy (plus or minus 2 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum Fructosamine Level |  | At 1 month | 
| Hemoglobin A1c |  | At 1 month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Induction chemotherapy, Transient hyperglycemia, Metformin, Acute lymphoblastic leukemia, Insulin resistance, Hyperglycemia, Insulin