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

Inclusion Criteria

• •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