Clinical trial NCT01486043: Metformin and Transient Hyperglycemia
Official title: Metformin as an Adjunctive Therapy For Transient Hyperglycemia in Patients With Acute Lymphoblastic Leukemia During Induction Chemotherapy
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Acute Lymphoblastic Leukemia
Hyperglycemia
Insulin Resistance
Diabetes Mellitus
Keywords: Induction chemotherapy
Transient hyperglycemia
Metformin
Acute lymphoblastic leukemia
Insulin resistance
Hyperglycemia
Insulin
Lead sponsor: Children's Hospital Los Angeles
Sponsor class: OTHER
First posted: 2011-12-06
Enrollment: 4
Sex: ALL
Minimum age (years): 10
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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%)

Primary outcomes:
measure: Length of Insulin Therapy (Days)
timeFrame: During the 30 days of induction chemotherapy (plus or minus 2 weeks)
Secondary outcomes:
measure: Serum Fructosamine Level
timeFrame: At 1 month
measure: Hemoglobin A1c
timeFrame: At 1 month
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles
state: California
Study officials:
affiliation: Children's Hospital Los Angeles
name: Jamie R Wood, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Pui CH, Burghen GA, Bowman WP, Aur RJ. Risk factors for hyperglycemia in children with leukemia receiving L-asparaginase and prednisone. J Pediatr. 1981 Jul;99(1):46-50. doi: 10.1016/s0022-3476(81)80955-9.
citation: Baillargeon J, Langevin AM, Mullins J, Ferry RJ Jr, DeAngulo G, Thomas PJ, Estrada J, Pitney A, Pollock BH. Transient hyperglycemia in Hispanic children with acute lymphoblastic leukemia. Pediatr Blood Cancer. 2005 Dec;45(7):960-3. doi: 10.1002/pbc.20320.
citation: Lowas SR, Marks D, Malempati S. Prevalence of transient hyperglycemia during induction chemotherapy for pediatric acute lymphoblastic leukemia. Pediatr Blood Cancer. 2009 Jul;52(7):814-8. doi: 10.1002/pbc.21980.
citation: Howard SC, Pui CH. Endocrine complications in pediatric patients with acute lymphoblastic leukemia. Blood Rev. 2002 Dec;16(4):225-43. doi: 10.1016/s0268-960x(02)00042-5.
citation: Sonabend RY, McKay SV, Okcu MF, Yan J, Haymond MW, Margolin JF. Hyperglycemia during induction therapy is associated with poorer survival in children with acute lymphocytic leukemia. J Pediatr. 2009 Jul;155(1):73-8. doi: 10.1016/j.jpeds.2009.01.072. Epub 2009 Apr 25.