Placebo Controlled Double Blind Crossover Trial of Metformin for Brain Repair in Children With Cranial-Spinal Radiation for Medulloblastoma | RxWiki

Placebo Controlled Double Blind Crossover Trial of Metformin for Brain Repair in Children With Cranial-Spinal Radiation for Medulloblastoma

Overview[ - collapse ][ - ]

Purpose	A placebo controlled double blind crossover trial of metformin in 30 children treated with radiation for medulloblastoma - the most common malignant brain tumour. The investigators will use tests of thinking and learning and brain imaging techniques to examine whether metformin can enhance cognition or promote brain repair following radiation-induced brain injury.
Condition	Medulloblastoma
Intervention	Drug: Metformin Drug: Placebo
Phase	Phase 3
Sponsor	The Hospital for Sick Children
Responsible Party	The Hospital for Sick Children
ClinicalTrials.gov Identifier	NCT02040376
First Received	January 7, 2014
Last Updated	April 11, 2014
Last verified	April 2014

Tracking Information[ + expand ][ + ]

First Received Date	January 7, 2014
Last Updated Date	April 11, 2014
Start Date	March 2014
Estimated Primary Completion Date	March 2016
Current Primary Outcome Measures	Efficacy of metformin in fostering brain repair [Time Frame: Change from baseline (1-3 weeks prior to start of first 12 week treatment course) to midpoint testing (1-3 weeks after completion of the first 12 week treatment course)] [Designated as safety issue: No]The efficacy of metformin in fostering brain repair will be evaluated using both: (a) novel neuro-imaging techniques sensitive to subtle brain changes that may reflect recovery of gliogenesis/neurogenesis, and (b) neuro-cognitive measures sensitive to cognitive morbidity associated with radiation injury. Efficacy of metformin in fostering brain repair [Time Frame: Change from baseline (1-3 weeks prior to start of first 12 week treatment course) to final testing (1-3 weeks after completion of the second 12 week treatment course)] [Designated as safety issue: No]The efficacy of metformin in fostering brain repair will be evaluated using both: (a) novel neuro-imaging techniques sensitive to subtle brain changes that may reflect recovery of gliogenesis/neurogenesis, and (b) neuro-cognitive measures sensitive to cognitive morbidity associated with radiation injury.
Current Secondary Outcome Measures	Not Provided

Descriptive Information[ + expand ][ + ]

Brief Title	Placebo Controlled Double Blind Crossover Trial of Metformin for Brain Repair in Children With Cranial-Spinal Radiation for Medulloblastoma
Official Title	Placebo Controlled Double Blind Crossover Trial of Metformin for Brain Repair in Children With Cranial-Spinal Radiation for Medulloblastoma
Brief Summary	A placebo controlled double blind crossover trial of metformin in 30 children treated with radiation for medulloblastoma - the most common malignant brain tumour. The investigators will use tests of thinking and learning and brain imaging techniques to examine whether metformin can enhance cognition or promote brain repair following radiation-induced brain injury.
Detailed Description	Not Provided
Study Type	Interventional
Study Phase	Phase 3
Study Design	Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Condition	Medulloblastoma
Intervention	Drug: Metformin Metformin and placebo doses will be 500 mg/m2 po daily given in 2 doses for one week and if there are no concerns increased to 1000 mg/m2 po daily given in 2 doses for the rest of the 12 week trial. The investigators will use the closest dose according to body surface area (250-500-750-1000) BID. Drug: Placebo Metformin and placebo doses will be 500 mg/m2 po daily given in 2 doses for one week and if there are no concerns increased to 1000 mg/m2 po daily given in 2 doses for the rest of the 12 week trial. The investigators will use the closest dose according to body surface area (250-500-750-1000) BID.
Study Arm (s)	Experimental: Group A (Crossover Group 1) Subjects assigned to this arm will receive metformin first, followed by a washout period and then placebo. Experimental: Group B (Crossover Group 2) Subjects assigned to this arm will receive placebo first, followed by a washout period and then metformin.

Recruitment Information[ + expand ][ + ]

Recruitment Status	Recruiting
Estimated Enrollment	30
Estimated Completion Date	March 2016
Estimated Primary Completion Date	March 2016
Eligibility Criteria	Inclusion criteria: Survivors will be included if they: 1. Have been treated with cranial-spinal radiation, 2. Are between 5 and 17 years of age at time of consent, and 3. Either declare English as their native language or have had at least two years of schooling in English at the time of their baseline assessment. 4. Have been diagnosed with a medulloblastoma at least 2 years ago, is not receiving active treatment and no more than 10 years may have elapsed between treatment with cranial-spinal radiation and time of the trial. Survivors with a shunt will be included in the trial, but will need to be identified prior to study enrollment to discuss any specific considerations for imaging. 5. Meet criteria for adequate organ function requirements: 1. Adequate renal function defined as: Creatinine clearance or radioisotope glomerular filtration rate (GFR) > 70ml/min/1.73 m2 or serum creatinine based on age/gender as follows: Maximum Serum Creatinine Level (mg/dL) 5 to < 10 years: Male = 1; Female = 1 10 to < 13 years: Male = 1.2; Female = 1.2 13 to < 16 years: Male = 1.5; Female = 1.4 ≥ 16 years: Male = 1.7; Female = 1.4 2. Adequate liver function defined as: Total bilirubin < 1.5 x upper limit of normal (ULN) for age, and, serum glutamate oxaloacetate transaminase (SGOT) (AST) or serum glutamate pyruvate transaminase (SGPT) (ALT) < 3 x upper limit of normal (ULN) for age. 6. Females of childbearing potential must have a negative pregnancy test result and must agree to use a medically acceptable method of contraception throughout the entire study period and for 30 days after the last dose of study drug. 7. Informed consent will be obtained from the participants and/or their legal guardians by study team members authorized to consent for this study. Exclusion criteria: Survivors will be excluded if they 1. Have a pre-morbid history (i.e., prior to tumour diagnosis) of traumatic brain injury, neurological disorder, visual or sensory impairment, cerebral palsy, developmental delay or learning disability. 2. Are receiving palliative care. 3. Are unable to participate in neuro-imaging without sedation as this is the primary outcome measure for the trial. 4. Are unable to swallow tablets. 5. Are unstable and/or insulin-dependent (Type 1) diabetic patients. 6. Have acute or chronic metabolic acidosis and/or lactic acidosis. 7. Any female patient or partner who has reached menarche and male patients who are not willing to use an effective method of contraception. 8. Patient who is pregnant or lactating and does not agree to stop breastfeeding while receiving trial treatment. 9. Have a history of renal disease or renal dysfunction e.g., as suggested by elevated serum creatinine levels (see 5.a. Inclusion criteria) or abnormal creatinine clearance. 10. Have a history of congestive heart failure requiring pharmacologic treatment. 11. Have a known hypersensitivity to metformin hydrochloride.
Gender	Both
Ages	5 Years
Accepts Healthy Volunteers	No
Contacts	Contact: Donald Mabbott, PhD 416-813-8875 donald.mabbott@sickkids.ca
Location Countries	Canada

Administrative Information[ + expand ][ + ]

NCT Number	NCT02040376
Other Study ID Numbers	1000039383
Has Data Monitoring Committee	No
Information Provided By	The Hospital for Sick Children
Study Sponsor	The Hospital for Sick Children
Collaborators	Not Provided
Investigators	Not Provided
Verification Date	April 2014

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