Metformin and Transient Hyperglycemia

This study has been terminated.
(The research projected was terminated due to lower than projected patient recruitment within the period of time allowed for the study.)
Sponsor:
Information provided by (Responsible Party):
Dr. Jamie R. Wood, Children's Hospital Los Angeles
ClinicalTrials.gov Identifier:
NCT01486043
First received: November 30, 2011
Last updated: July 21, 2014
Last verified: July 2014
  Purpose

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


Condition Intervention
Acute Lymphoblastic Leukemia
Hyperglycemia
Insulin Resistance
Diabetes Mellitus
Drug: Metformin

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Metformin as an Adjunctive Therapy For Transient Hyperglycemia in Patients With Acute Lymphoblastic Leukemia During Induction Chemotherapy

Resource links provided by NLM:


Further study details as provided by Children's Hospital Los Angeles:

Primary Outcome Measures:
  • Length of insulin therapy (days) [ Time Frame: During the 30 days of induction chemotherapy (plus or minus 2 weeks) ] [ Designated as safety issue: No ]
    Total number of days of insulin therapy will vary among subjects with different degee of insulin resistance and insulin need. We will be monitoring lenghth of insulin therapy until subject is weaned off insulin, which typically occurs in 1-2 weeks after completion of induction chemotherapy.


Secondary Outcome Measures:
  • Total daily dose of insulin (unit of insulin per kilogram of subject's weight [ Time Frame: During the 30 days of induction chemotherapy (plus or minus 2 weeks) ] [ Designated as safety issue: No ]
  • Number of insulin injections per day [ Time Frame: During the 30 days of induction chemotherapy (plus or minus 2 weeks) ] [ Designated as safety issue: No ]
  • Serum fructosamine level [ Time Frame: On day 1 of study (prior to initiation of insulin and metformin therapy) and at 1 month ] [ Designated as safety issue: No ]
  • Length of hospital stay (days) [ Time Frame: During the first 30 days of induction chemotherapy ] [ Designated as safety issue: No ]
  • Hemoglobin A1c [ Time Frame: On day 1 of study (prior to initiation of insulin and metformin therapy) ] [ Designated as safety issue: No ]

Enrollment: 2
Study Start Date: December 2011
Study Completion Date: May 2013
Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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
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.
Other Name: Glucophage, Metformin HCl

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

Ages Eligible for Study:   10 Years to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 and ALT < 2.5x 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%)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01486043

Locations
United States, California
Children's Hospital Los Angeles
Los Angeles, California, United States, 90027
Sponsors and Collaborators
Children's Hospital Los Angeles
Investigators
Principal Investigator: Jamie R Wood, M.D. Children's Hospital Los Angeles
  More Information

Publications:
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, Children's Hospital Los Angeles
ClinicalTrials.gov Identifier: NCT01486043     History of Changes
Other Study ID Numbers: CCI-11-00295
Study First Received: November 30, 2011
Last Updated: July 21, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Children's Hospital Los Angeles:
Induction chemotherapy
Transient hyperglycemia
Metformin
Acute lymphoblastic leukemia
Insulin resistance
Hyperglycemia
Insulin

Additional relevant MeSH terms:
Diabetes Mellitus
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Leukemia
Insulin Resistance
Hyperglycemia
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Hyperinsulinism
Metformin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 18, 2014