Metformin and Transient Hyperglycemia

Diabetes Mellitus Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01486043
• Other study ID #: CCI-11-00295
• Status: Terminated
• Phase: N/A
• First received: November 30, 2011
• Last updated: January 20, 2015
• Start date: December 2011
• Est. completion date: May 2013

Study information

• Verified date: January 2015
• Source: Children's Hospital Los Angeles
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 4
• Est. completion date: May 2013
• Est. primary completion date: May 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 10 Years to 21 Years

Eligibility

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%)

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Lymphoblastic Leukemia
• Diabetes Mellitus
• Hyperglycemia
• Insulin Resistance
• Leukemia, Lymphoid
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Drug:
• 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.

Locations

Country	Name	City	State
United States	Children's Hospital Los Angeles	Los Angeles	California

Sponsors (1)

Lead Sponsor	Collaborator
Children's Hospital Los Angeles

Country where clinical trial is conducted

United States, 

References & Publications (5)

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. — View Citation

Howard SC, Pui CH. Endocrine complications in pediatric patients with acute lymphoblastic leukemia. Blood Rev. 2002 Dec;16(4):225-43. Review. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Length of Insulin Therapy (Days)		During the 30 days of induction chemotherapy (plus or minus 2 weeks)	No
Secondary	Serum Fructosamine Level		At 1 month	No
Secondary	Hemoglobin A1c		At 1 month	No