Metformin and Transient Hyperglycemia

• Sponsor: Children's Hospital Los Angeles (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01486043
• Collaborator: (none)
• Enrollment: 4
• Location: 1
• Arm: 1
• Duration (Months): 17
• Patients Per Site Per Month: 0.2

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Acute Lymphoblastic Leukemia; Hyperglycemia; Insulin Resistance; Diabetes Mellitus	Drug: Metformin	N/A

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 4 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Metformin as an Adjunctive Therapy For Transient Hyperglycemia in Patients With Acute Lymphoblastic Leukemia During Induction Chemotherapy
• Study Start Date: Dec 1, 2011
• Actual Primary Completion Date: May 1, 2013
• Actual Study Completion Date: May 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
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 Names: Glucophage, Metformin HCl

Outcome Measures

Primary Outcome Measures

1. Length of Insulin Therapy (Days) [During the 30 days of induction chemotherapy (plus or minus 2 weeks)]

Secondary Outcome Measures

1. Serum Fructosamine Level [At 1 month]

2. Hemoglobin A1c [At 1 month]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 10 Years to 21 Years
• Sexes Eligible for Study: All
• Accepts 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%)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	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

Study Documents (Full-Text)

None provided.

More Information

Publications

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

• 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
• Other Study ID Numbers: CCI-11-00295
• First Posted: Dec 6, 2011
• Last Update Posted: Jan 30, 2015
• Last Verified: Jan 1, 2015

• Keywords provided by 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: Induction chemotherapy; Transient hyperglycemia; Metformin; Acute lymphoblastic leukemia; Insulin resistance; Hyperglycemia; Insulin
• Additional relevant MeSH terms: Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Insulin Resistance; Hyperglycemia; Metformin

Study Results

Participant Flow

Arm/Group Title	Metformin and Insulin Therapy
Arm/Group Description	For the prospectively recruited arm (metformin plus insulin therapy), a total of 4 subjects were recruited. Two subjects were withdrawn from the study after laboratory studies revealed liver enzymes (AST) levels that were above that allowed for the study at the time. An additional 2 subjects were recruited in the study. For the retrospective chart review portion of our study, 12 patients were included after conducting chart review of cases from January 2007 to August 2011.
Period Title: Overall Study
STARTED	4
COMPLETED	2
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	Metformin and Insulin Therapy
Arm/Group Description	Patients receiving metformin and insulin therapy.
Overall Participants	2
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	13.5
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	2 100%
Region of Enrollment (participants) [Number]
United States	2 100%
Hemoglobin A1C (%) [Mean (Full Range) ]
Mean (Full Range) [%]	5.8
Fructosamine (uM) [Mean (Full Range) ]
Mean (Full Range) [uM]	193
# of Day of Induction at Onset of Hyperglycemia (days) [Mean (Full Range) ]
Mean (Full Range) [days]	2

Outcome Measures

1. Primary Outcome

Title	Length of Insulin Therapy (Days)
Time Frame	During the 30 days of induction chemotherapy (plus or minus 2 weeks)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Metformin and Insulin Therapy
Arm/Group Description	Patients receiving metformin and insulin therapy.
Measure Participants	2
Mean (Full Range) [days]	7.5

2. Secondary Outcome

Title	Serum Fructosamine Level
Time Frame	At 1 month

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Metformin and Insulin Therapy
Arm/Group Description	Patients receiving metformin and insulin therapy.
Measure Participants	2
Mean (Full Range) [uM]	190

3. Secondary Outcome

Title	Hemoglobin A1c
Time Frame	At 1 month

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Metformin and Insulin Therapy
Arm/Group Description	Patients receiving metformin and insulin therapy.
Measure Participants	2
Mean (Full Range) [percent of hemoglobin]	4.8

Adverse Events

Arm/Group Title	Metformin and Insulin Therapy
Arm/Group Description	Patients receiving metformin and insulin therapy.
All Cause Mortality
	Metformin and Insulin Therapy
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Metformin and Insulin Therapy
	Affected / at Risk (%)	# Events
Total	0/4 (0%)
Other (Not Including Serious) Adverse Events
	Metformin and Insulin Therapy
	Affected / at Risk (%)	# Events
Total	0/4 (0%)

Limitations/Caveats

Early termination leading to small numbers of subjects analyzed.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.