Health TrialsbyHealthPanel

Effect of Metformin on Behaviour and the Brain in Children Treated for a Brain Tumour

ConditionsMedulloblastoma, ChildhoodCognitive Impairment
Trial statusRecruiting
Trial phasePhase 3
Trial typeInterventional
Biological sexAll
Age7-21
SponsorDonald Mabbott

About this trial

The efficacy of treatment with metformin for promoting cognitive recovery and brain growth in children/adolescents treated for a brain tumour will be investigated in a multi-site Phase III randomized double-blind placebo-controlled parallel arm superiority trial. Specifically, in children/adolescents aged 7 years to 21 years and 11 months who have completed treatment for a brain tumour, is oral administration of metformin for 16 weeks associated with greater improvement of cognitive function and brain growth compared to placebo administered for 16 weeks?

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

medulloblastoma

ependymoma

craniopharyngioma

germ cell tumours

Disqualifiers

Standard score of less than 60 for full scale IQ on the Wechsler Abbreviated Scale of Intelligence, Second Edition (WASI-II) (or other Wechsler Scale of Intelligence for English speaking participants) or pro-rated IQ score on the Wechsler Intelligence Scale for Children, Fifth Edition (WISC-V) or Wechsler Adult Intelligence Scale (WAIS-IV) for French speaking participants at Screening visit

Have a known hypersensitivity to metformin hydrochloride

Have unstable and/or insulin-dependent (Type 1) diabetes

Have a history of hypoglycemia after 2 years of age

Trial design

Design model

Parallel

Treatments tested in this trial

  • Metformin hydrochloride (HCl) 500mg tablet

    Drug

    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.

  • Placebo

    Drug

    Matching white round tablet containing excipients only. The placebo tablets will match the active drug as closely as possible in terms of appearance.

Treatment groups

140 Participants
are divided into 2 treatment groups
Group A: MetforminExperimental treatment 1 intervention
Group B: PlaceboPlacebo comparator 1 intervention

Trial outcomes

Primary outcomes

1

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

To examine the effectiveness of 16 weeks of treatment with metformin versus 16 weeks of placebo for improving cognition, as measured by CAVLT-2/RAVLT which is a test of auditory verbal learning and memory.

Time frame
Week 1 (Baseline), Week 17 (Post-Intervention)
2

Change from Week 1 (Baseline) NIH Toolbox List Sort Working Working Memory Test at Week 17 (Post-Intervention) to Assess Working Memory

To examine the effectiveness of 16 weeks of treatment with metformin versus 16 weeks of placebo for improving cognition, as measured by List Sorting Working Memory Test (LSWMT) in which participants will be required to recall and place in sequence stimuli that are presented visually and verbally.

Time frame
Week 1 (Baseline), Week 17 (Post-Intervention)
3

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

To examine the effectiveness of 16 weeks of treatment with metformin versus 16 weeks of placebo for improving cognition, as measured by mean reaction time for correct trials across subtests of the CANTAB: 1. Rapid Visual Information Processing (RVP) 2. Reaction Time (RTI) 3. Match to Sample Visual Search (MTS) 4. Delayed Matching to Sample (DMS) Each subtest provides an outcome measure of response latency, which will be averaged across all correct trials for each subtest to provide an overall measure of processing speed.

Time frame
Week 1 (Baseline), Week 17 (Post-Intervention)

Secondary outcomes

1

Diffusion Kurtosis Imaging (DKI) to Assess White Matter Growth within the Corpus Callosum

To examine the effectiveness of 16 weeks of treatment with metformin versus 16 weeks of placebo for promoting white matter growth within the corpus callosum as measured by DKI including axonal water fraction (AWF), a metric sensitive to myelin. This secondary outcome measure (MRI scan) was made optional to participants enrolled after April 2024.

Time frame
Week 1 (Baseline), Week 17 (Post-Intervention)

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Donald Mabbott

Lead sponsor

The Hospital for Sick Children

Sponsor institution

Source ClinicalTrials.gov
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