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The research project was terminated due to lower than projected patient recruitment within the period of time allowed for the study.
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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
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Metformin and insulin therapy | Experimental | Up to 30-40 patients will be in the prospectively recruited treatment group, which will receive both metformin and insulin therapy for transient hyperglycemia |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Metformin | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Length of Insulin Therapy (Days) | During the 30 days of induction chemotherapy (plus or minus 2 weeks) |
| Measure | Description | Time Frame |
|---|---|---|
| Serum Fructosamine Level | At 1 month | |
| Hemoglobin A1c | At 1 month |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Jamie R Wood, M.D. | Children's Hospital Los Angeles | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Children's Hospital Los Angeles | Los Angeles | California | 90027 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 6454771 | Background | 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. | |
| 15700246 | Background | 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. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Metformin and Insulin Therapy | 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Metformin and Insulin Therapy | Patients receiving metformin and insulin therapy. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Length of Insulin Therapy (Days) | Posted | Mean | Full Range | days | During the 30 days of induction chemotherapy (plus or minus 2 weeks) |
|
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Metformin and Insulin Therapy | Patients receiving metformin and insulin therapy. |
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Early termination leading to small numbers of subjects analyzed.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Jamie Wood | Children's Hospital Los Angeles | 323-361-7388 | jawood@chla.usc.edu |
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| ID | Term |
|---|---|
| D054198 | Precursor Cell Lymphoblastic Leukemia-Lymphoma |
| D006943 | Hyperglycemia |
| D007333 | Insulin Resistance |
| D003920 | Diabetes Mellitus |
| ID | Term |
|---|---|
| D007945 | Leukemia, Lymphoid |
| D007938 | Leukemia |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
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| ID | Term |
|---|---|
| D008687 | Metformin |
| ID | Term |
|---|---|
| D001645 | Biguanides |
| D006146 | Guanidines |
| D000578 | Amidines |
| D009930 | Organic Chemicals |
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|
| 19260096 | Background | 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. |
| 12350366 | Background | 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. |
| 19394046 | Background | 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. |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Hemoglobin A1C | Mean | Full Range | % |
|
| Fructosamine | Mean | Full Range | uM |
|
| # of Day of Induction at Onset of Hyperglycemia | Mean | Full Range | days |
|
|
| Secondary | Serum Fructosamine Level | Posted | Mean | Full Range | uM | At 1 month |
|
|
|
| Secondary | Hemoglobin A1c | Posted | Mean | Full Range | percent of hemoglobin | At 1 month |
|
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| 0 |
| 4 |
| 0 |
| 4 |
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| D006402 |
| Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D006946 | Hyperinsulinism |
| D004700 | Endocrine System Diseases |