Metformin for Brain Repair in Children With Cranial-Spinal Radiation for Medulloblastoma

Inclusion criteria: Survivors will be included if they:

1. Have been treated with cranial or cranial-spinal radiation,

2. Are between 5 and 21 years of age at time of consent, and

3. Either declare English as their native language or have had at least two years ofschooling in English at the time of their baseline assessment.

4. Have been diagnosed with a brain tumour requiring treatment with cranial orcranial-spinal radiation at least 2 years ago, is not receiving active treatment andno more than 15 years may have elapsed between treatment with cranial-spinalradiation and time of the trial. Survivors with a shunt will be included in thetrial, but will need to be identified prior to study enrollment to discuss anyspecific considerations for imaging.

5. Meet criteria for adequate organ function requirements:

6. Adequate renal function defined as: Creatinine clearance or radioisotopeglomerular filtration rate (GFR) > 70ml/min/1.73 m2 or serum creatinine basedon 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

7. 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 pyruvatetransaminase (SGPT) (ALT) < 3 x upper limit of normal (ULN) for age.

8. Females of childbearing potential must have a negative pregnancy test result andmust agree to use a medically acceptable method of contraception throughout theentire study period and for 30 days after the last dose of study drug.

9. Informed consent will be obtained from the participants and/or their legal guardiansby study team members authorized to consent for this study.

Exclusion criteria: Survivors will be excluded if they

1. Are receiving palliative care.

2. Are unable to participate in neuro-imaging without sedation as this is the primaryoutcome measure for the trial.

3. Are unable to swallow tablets.

4. Are unstable and/or insulin-dependent (Type 1) diabetic patients.

5. Have acute or chronic metabolic acidosis and/or lactic acidosis.

6. Any female patient or partner who has reached menarche and male patients who are notwilling to use an effective method of contraception.

7. Patient who is pregnant or lactating and does not agree to stop breastfeeding whilereceiving trial treatment.

8. Have a history of renal disease or renal dysfunction e.g., as suggested by elevatedserum creatinine levels (see 5.a. Inclusion criteria) or abnormal creatinineclearance.

9. Have a history of congestive heart failure requiring pharmacologic treatment.

10. Have a known hypersensitivity to metformin hydrochloride.