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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05230758




Registration number
NCT05230758
Ethics application status
Date submitted
12/01/2022
Date registered
9/02/2022

Titles & IDs
Public title
Effect of Metformin on Behaviour and the Brain in Children Treated for a Brain Tumour
Scientific title
Phase III Randomized Double-blind Placebo-controlled Trial of Metformin for Cognitive Recovery and White Matter Growth in Paediatric Medulloblastoma Patients
Secondary ID [1] 0 0
1000073107
Universal Trial Number (UTN)
Trial acronym
Met Med Can
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Medulloblastoma, Childhood 0 0
Cognitive Impairment 0 0
Condition category
Condition code
Cancer 0 0 0 0
Children's - Brain
Cancer 0 0 0 0
Brain

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Metformin hydrochloride (HCl) 500mg tablet
Treatment: Drugs - Placebo

Experimental: Metformin - Oral metformin will be administered approximately 500mg/m2/day for 1 week and increased to 1000mg/m2/day for 15 weeks. Doses will be rounded to increments of half tablets (250mg, 500mg, 750mg and 1000mg).

Placebo comparator: Placebo - Oral placebo will be administered approximately 500mg/m2/day for 1 week and increased to 1000mg/m2/day for 15 weeks. Doses will be rounded to increments of half tablets (250mg, 500mg, 750mg and 1000mg).


Treatment: Drugs: Metformin hydrochloride (HCl) 500mg tablet
Metformin HCl 500mg tablets contain 500mg of active pharmaceutical ingredient (API) and are white, round, biconvex, film-coated tablets, with a score line on one face and debossed with "HMR" on the other. Each tablet contains the non-medicinal ingredients magnesium stearate and povidone. Tablet coating is comprised of hydroxypropyl methylcellulose, polyethylene glycol and titanium dioxide.

Treatment: Drugs: Placebo
Matching white round tablet containing excipients only. The placebo tablets will match the active drug as closely as possible in terms of appearance.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change from Week 1 (Baseline) Children's Auditory Verbal Learning Test-2 (CAVLT-2)/Rey Auditory Verbal Learning Test (RAVLT) Immediate Recall at Week 17 (Post-Intervention) to Assess Declarative Memory
Timepoint [1] 0 0
Week 1 (Baseline), Week 17 (Post-Intervention)
Primary outcome [2] 0 0
Change from Week 1 (Baseline) NIH Toolbox List Sort Working Working Memory Test at Week 17 (Post-Intervention) to Assess Working Memory
Timepoint [2] 0 0
Week 1 (Baseline), Week 17 (Post-Intervention)
Primary outcome [3] 0 0
Change from Week 1 (Baseline) Cambridge Neuropsychological Test Automated Battery (CANTAB) Mean Reaction Time for Correct Trials across the RVP, RTI, MTS, and DMS Subtests at Week 17 (Post-Intervention) to Assess Processing Speed
Timepoint [3] 0 0
Week 1 (Baseline), Week 17 (Post-Intervention)
Secondary outcome [1] 0 0
Diffusion Kurtosis Imaging (DKI) to Assess White Matter Growth within the Corpus Callosum
Timepoint [1] 0 0
Week 1 (Baseline), Week 17 (Post-Intervention)

Eligibility
Key inclusion criteria
In order to be eligible to participate in this study, an individual must meet all of the following criteria:

1. No less than 3 weeks after completion of primary therapy for medulloblastoma
2. Age 7 years to 17 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:

1. 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/dL
2. 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 <1.5x 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
Minimum age
7 Years
Maximum age
17 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Participants who meet any of the following criteria will not be eligible to take part in the trial:

1. Unable to participate in MRI without sedation
2. Standard score of less than 60 for full scale IQ on the Wechsler Abbreviated Scale of Intelligence, Second Edition (WASI-II) (for English speaking participants) or pro-rated IQ score on the Wechsler Intelligence Scale for Children, Fifth Edition (WISC-V) (for French speaking participants) at Screening visit
3. Have a known hypersensitivity to metformin hydrochloride
4. Have unstable and/or insulin-dependent (Type 1) diabetes
5. Have a history of hypoglycemia after 2 years of age
6. 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
7. Have a history of renal disease or renal dysfunction
8. Have a history of congestive heart failure requiring pharmacologic treatment (including the use of diuretics) within two years prior to study entry
9. Currently taking part in a cognitive rehabilitation intervention study
10. Treatment or planned treatment involving diuretics
11. 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)
12. 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.
13. Pernicious anemia (according to results of the Screening visit blood draw)
14. Current use of metformin hydrochloride
15. 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

Study design
Purpose of the study
Other
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/07/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
30/06/2027
Actual
Sample size
Target
140
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC,West Australi
Recruitment hospital [1] 0 0
John Hunter Children's Hospital - New Lambton Heights
Recruitment hospital [2] 0 0
Children's Hospital in Westmead - Westmead
Recruitment hospital [3] 0 0
Monash Children's Hospital - Clayton
Recruitment hospital [4] 0 0
Royal Children's Hospital - Parkville
Recruitment hospital [5] 0 0
Perth Children's Hospital - Nedlands
Recruitment postcode(s) [1] 0 0
2305 - New Lambton Heights
Recruitment postcode(s) [2] 0 0
2145 - Westmead
Recruitment postcode(s) [3] 0 0
3168 - Clayton
Recruitment postcode(s) [4] 0 0
3052 - Parkville
Recruitment postcode(s) [5] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
Canada
State/province [1] 0 0
Alberta
Country [2] 0 0
Canada
State/province [2] 0 0
British Columbia
Country [3] 0 0
Canada
State/province [3] 0 0
Manitoba
Country [4] 0 0
Canada
State/province [4] 0 0
Nova Scotia
Country [5] 0 0
Canada
State/province [5] 0 0
Ontario
Country [6] 0 0
Canada
State/province [6] 0 0
Quebec
Country [7] 0 0
Canada
State/province [7] 0 0
Saskatchewan

Funding & Sponsors
Primary sponsor type
Other
Name
Donald Mabbott
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Donald Mabbott, Ph.D.
Address 0 0
The Hospital for Sick Children
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Cynthia de Medeiros, M.Sc.
Address 0 0
Country 0 0
Phone 0 0
416-813-7396
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT05230758