None listed
Conditions
Brief summary
The purpose of this study is to test whether metformin treatment is associated with greater improvement of cognitive function and brain growth compared to placebo group for children/adolescents with a brain tumour. Who is it for? You may be eligible to participate in this study if you are between 7 years and 21 years and 11 months old and have been treated for a brain tumour. Study Details Participants will be required to take oral medication in tablet form daily for 16 weeks. 'Participants will be randomly allocated to receive either metformin as an oral tablet taken daily or a placebo tablet. Participation in this trial will require an overall time commitment of 40 weeks as participants must undergo screening and pre-treatment assessments and as well as a 6 month post-treatment follow-up. Assessments will include MRI scans and cognitive testing to measure memory, attention and processing speed. It is hoped that this research will help to determine if metformin has a positive effect on cognitive and brain recovery from brain cancer in this population
Interventions
For all participants in the treatment group, the intervention is as follows:
Week 1: 500mg/m^2 metformin hydrochloride tablet administered orally once per day
Weeks 2-16: 1000 mg/m^2 metformin hydrochloride tablet administered orally once per day
Doses will be rounded to increments of half tablets (250mg, 500mg, 750mg and 1000mg).
Pill counts will be conducted to calculate percent adherence to therapy based on the number of pills consumed vs. anticipated pill consumption.
Sponsors
The Hospital for Sick Children (SickKids), Canada
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
84 Months to 263 Months
Healthy volunteers
No
Inclusion criteria
1. No less than 3 weeks after completion of: • Primary therapy for: a) medulloblastoma OR b) ependymoma OR c) craniopharyngioma OR d) germ cell tumours OR • Primary therapy for any other brain tumour treated with cranial radiation - at the discretion of the Study PI OR • Cranial radiation for relapsed ependymoma 2. Age 7 years to 21 years and 11 months at the time of enrollment 3. Either declare English (or French in accepting sites) as their native language or have had at least two years of schooling in English (or French in accepting sites) at the time of consent 4. Able to swallow tablets either whole, crushed or via a feeding tube and be willing to adhere to the study intervention regimen 5. Meet criteria for normal organ function requirements as described below: a. Normal renal function defined as: Estimated glomerular filtration rate (eGFR) > 75ml/min/1.73m2 • eGFR is calculated using the Schwartz formula: eGFR (mL/min/1.73m²) = (0.41 × height in cm) / creatinine in mg/dL114,115 b. Normal liver function defined as: • Serum glutamic-oxaloacetic transaminase (SGOT) (AST) =2.5 x institutional upper limit of normal (ULN) for age and gender • Serum glutamic pyruvic transaminase (SGPT) (ALT) =2.5 x institutional ULN for age and gender • Total bilirubin (conjugated + unconjugated) <1.5 x institutional ULN for age and gender (patients with documented Gilbert’s Disease may be enrolled with Sponsor approval and total bilirubin =2.0 x institutional ULN) 6. Informed consent (and assent, where applicable) will be obtained from the participants and/or their legal guardian(s) by study team members delegated to consent for this study
Exclusion criteria
1. Standard score of less than 60 for full scale IQ on the WASI-II (or other equivalent Wechsler Scale of Intelligence for English speaking participants) or pro-rated IQ score on the WISC-V or WAIS-IV (for French speaking participants) at Screening visit 2. Have a known hypersensitivity to metformin hydrochloride 3. Have unstable and/or insulin-dependent (Type 1) diabetes 4. Have a history of hypoglycemia after 2 years of age 5. Have been diagnosed with acute or chronic metabolic acidosis and/or lactic acidosis or if bicarbonate (Total CO2) is less than 22 mmol/L at the Screening visit 6. Have a history of renal disease or renal dysfunction pre-existing to the brain tumour diagnosis 7. Have a history of congestive heart failure requiring pharmacologic treatment (including the use of diuretics) within two years prior to study entry 8. Currently taking part in a cognitive rehabilitation intervention study 9. Treatment or planned treatment involving diuretics 10. 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) 11. Current or planned treatment with concomitant medications with potential unacceptable interaction with metformin including lamotrigine, beta blockers, angiotensin-converting enzyme (ACE) inhibitors, glycopyrrolate, and carbonic anhydrase inhibitors, or at the discretion of the Site PI or delegate for medications with potential interactions such as sertraline, lansoprazole and omeprazole. 12. Pernicious anemia (according to results of the Screening visit blood draw) 13. Current use of metformin hydrochloride 14. Any condition or diagnosis, that could in the opinion of the Site PI or delegate interfere with the participant’s ability to comply with study instructions, might confound the interpretation of the study results, or put the participant at risk 15. Are receiving palliative care
Outcome results
None listed