Metformin and Transient Hyperglycemia

NCT ID: NCT01486043

Last Updated: 2015-01-30

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: NA
• Total Enrollment: 4 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-12-31
• Study Completion Date: 2013-05-31

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.

Conditions

Acute Lymphoblastic Leukemia; Hyperglycemia; Insulin Resistance; Diabetes Mellitus

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Metformin and insulin therapy

Up to 30-40 patients will be in the prospectively recruited treatment group, which will receive both metformin and insulin therapy for transient hyperglycemia

Group Type: EXPERIMENTAL

Metformin

Intervention Type: DRUG

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.

Interventions

Metformin

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.

Intervention Type: DRUG

Other Intervention Names

Glucophage, Metformin HCl

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%)

• Minimum Eligible Age: 10 Years
• Maximum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Children's Hospital Los Angeles

OTHER

Sponsor Role: lead

Responsible Party

Dr. Jamie R. Wood

Assistant Professor of Clinical Pediatrics; Director of Clinical Diabetes Programs at Children's Hospital Los Angeles, University of Southern California, Keck School of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jamie R Wood, M.D.

Role: PRINCIPAL_INVESTIGATOR

Children's Hospital Los Angeles

Locations

Children's Hospital Los Angeles

Los Angeles, California, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 6454771 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 15700246 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 19260096 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 12350366 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 19394046 (View on PubMed)

Other Identifiers

CCI-11-00295

Identifier Type: -

Identifier Source: org_study_id