Metformin for Motor and Cognitive Improvement in Children With Cerebral Palsy: A Feasibility Study

Inclusion criteria are as follows: 1. Physician diagnosis of cerebral palsy defined "as a group of permanent disorders of the development of movement and posture causing activity limitation that is attributed to non-progressive disturbances that occurred in the developing fetal or infant brain." 2. Evidence of WMI or GMI pattern on prior clinical neuro-imaging scanning (MRI) 3. No history of hypoglycemia after 2 years of age 4. No aspiration pneumonias in the last year requiring hospitalization 5. No lower extremity orthopedic surgery in the last six months prior to trial entry 6. No acute or chronic metabolic acidosis and/or lactic acidosis over the lifespan, including a lactate level greater than 2.4 mmol/L at the screening visit. 7. No history of renal disease 8. Age 5 to 18 years, 11 months at the time of enrollment 9. 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 10. Gross Motor Function Classification System Level of II - V at the time of enrollment 11. Ability to communicate (verbal or non-verbal) pain or discomfort 12. With the exception of physiotherapy, no participation in active gross motor rehabilitation treatment (e.g. receiving lower extremity botulinum toxin injections, engaged in robotic walking therapy) up to 4 months prior to trial entry period and willingness to forgo introducing any new CP treatments during the 16 week trial period 13. Able to consume whole or crushed tablets swallowed orally or through a gastrostomy tube 14. Ability to understand and follow single step instructions/commands (i.e. blinking eyes, opening mouth, and moving head side to side). 15. Meet criteria for normal organ function requirements as described below: Normal renal function defined as: Estimated glomerular filtration rate (eGFR) \> 75ml/min/1.73m2 1. eGFR is calculated using the Schwartz formula: eGFR (mL/min/1.73 m²) = (0.41 × Height in cm) / Creatinine in mg/dL \[29, 30\] 2. Normal liver function defined as: * Total bilirubin \< upper limit of normal (ULN) for age * SGOT (AST) or SGPT (ALT) \< upper limit of normal (ULN) for age Maximum AST Level (U/L) Male Female \<12 years \<47 \<47 ≥ 12 years \<35 \<30 Maximum ALT Level (U/L) Male Female All Ages \<50 \<36 Maximum Total Billirubin Level ( μmol/L) Male Female All Ages \<20 \<20 Informed consent (and assent, where applicable) will be obtained from the participants by study team members authorized to consent for this study Exclusion criteria are as follows: Participants who meet any of the following criteria will not be eligible to take part in the trial: 1. No prior clinically ordered neuro-imaging to allow determination of WMI or GMI 2. Have a known hypersensitivity to metformin hydrochloride or any of the excipients 3. Have Diabetes (Type I or II) 4. Have taken oral metformin previously 5. Have been part of another clinical intervention study within the past 3 months prior to study entry 6. Require sedation for blood tests 7. Treatment or planned treatment involving diuretics 8. Current or planned treatment with cationic drugs excreted by the kidneys (e.g. amiloride, cimetidine, digoxin, morphine, nifedipine, procainamide, quinidine, quinine, ranitidine, triamterene, trimethoprim and vancomycin). 9. Current or planned treatment with concomitant medications with potential unacceptable interaction with metformin including topiramate, lamotrigine, levetiracetam, beta blockers, ACE inhibitors, glycopyrrolate, and carbonic anhydrase inhibitors, or at the discretion of the delegated study physician for medications with potential interactions such as sertraline, lansoprazole and omeprazole. 10. Receiving deep brain stimulation or intrathecal baclofen 11. Dosage of oral baclofen and benzodiazepines stabilized for less than 2 months prior to study entry, and/or planning to change the dosage over the treatment period (if applicable) 12. Females who are pregnant, nursing, or planning a pregnancy during the study 13. Pernicious anemia (according to results of the screening visit blood draw) 14. Weight for age percentile less than 5% 15. Uncontrolled seizures with or without medication (defined by a seizure lasting longer than 10 minutes in duration within six months prior to study entry or change in seizure medication due to poor seizure control in the 3 months prior to trial entry). 16. History of congestive heart failure (including the use of diuretics) requiring pharmacologic treatment within two years prior to study entry