Acute Lymphoblastic Leukemia, Diabetes Mellitus, Hyperglycemia, Insulin Resistance
Conditions
Keywords
Induction chemotherapy, Transient hyperglycemia, Metformin, Acute lymphoblastic leukemia, Insulin resistance, Hyperglycemia, Insulin
Brief summary
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
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.
Interventions
DRUGMetformin
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.
Sponsors
Children's Hospital Los Angeles
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
10 Years to 21 Years
Healthy volunteers
No
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%)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Length of Insulin Therapy (Days) | During the 30 days of induction chemotherapy (plus or minus 2 weeks) |
Secondary
| Measure | Time frame |
|---|---|
| Serum Fructosamine Level | At 1 month |
| Hemoglobin A1c | At 1 month |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Metformin and Insulin Therapy Patients receiving metformin and insulin therapy. | 2 |
| Total | 2 |
Baseline characteristics
| Characteristic | Metformin and Insulin Therapy |
|---|---|
| Age, Continuous | 13.5 years |
| Fructosamine | 193 uM |
| Hemoglobin A1C | 5.8 % |
| # of Day of Induction at Onset of Hyperglycemia | 2 days |
| Region of Enrollment United States | 2 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 4 |
| serious Total, serious adverse events | 0 / 4 |
Outcome results
Primary
Length of Insulin Therapy (Days)
Time frame: During the 30 days of induction chemotherapy (plus or minus 2 weeks)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Metformin and Insulin Therapy | Length of Insulin Therapy (Days) | 7.5 days |
Secondary
Hemoglobin A1c
Time frame: At 1 month
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Metformin and Insulin Therapy | Hemoglobin A1c | 4.8 percent of hemoglobin |
Secondary
Serum Fructosamine Level
Time frame: At 1 month
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Metformin and Insulin Therapy | Serum Fructosamine Level | 190 uM |