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Metformine voor hersenherstel bij kinderen met craniale-spinale straling voor medulloblastoom

21 september 2026 bijgewerkt door: Donald Mabbott, The Hospital for Sick Children

Placebo-gecontroleerde dubbelblinde crossover-studie met metformine voor hersenherstel bij kinderen met craniale-spinale bestraling voor medulloblastoom

A placebo controlled double blind crossover trial of metformin in 30 children treated with radiation for medulloblastoma - the most common malignant brain tumour. The investigators used tests of thinking and learning and brain imaging techniques to examine whether metformin can enhance cognition or promote brain repair following radiation-induced brain injury.

Studie Overzicht

Toestand

Voltooid

Conditie

Interventie / Behandeling

Gedetailleerde beschrijving

We conducted a pilot randomized, double-blind, placebo-controlled trial with crossover in survivors of pediatric brain tumors with primary endpoints of safety and feasibility and secondary endpoints of cognitive and magnetic resonance imaging (MRI) measures. Twenty-four participants were enrolled and randomly assigned to complete 12-week cycles of metformin (A) and placebo (B) in either a group AB (AB) or group BA (BA) sequence. At the point of crossover, there was a 10-week washout period in which neither group received any treatment. During the first week of each treatment cycle, a daily dose of 500 mg/m2 of metformin or placebo was administered orally. The dose was increased to 1000mg/m2 daily beginning in the second week and continuing for the remainder of the 12-week cycle.

Test procedures (Clinical & current medications reviews, Blood draws, and MRI and Cognitive testing) were performed at 4 times points during the study: 1. at study entry (Baseline 1), 2. after 12 weeks of treatment (Outcome 1), 3. after a 10-week washout period at 22 weeks (Baseline 2), and 4. At the end of the trial at 34 weeks (Outcome 2).

Studietype

Ingrijpend

Inschrijving (Werkelijk)

24

Fase

  • Fase 3

Contacten en locaties

In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.

Studie Locaties

  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5G 1X8
        • The Hospital for Sick Children

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

5 jaar tot 21 jaar (Kind, Volwassen)

Accepteert gezonde vrijwilligers

Nee

Geslachten die in aanmerking komen voor studie

Allemaal

Beschrijving

Inclusion criteria: Survivors will be included if they:

  1. Have been treated with cranial or cranial-spinal radiation,

  2. Are between 5 and 21 years of age at time of consent, and

  3. 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.

  4. Have been diagnosed with a brain tumour requiring treatment with cranial or cranial-spinal radiation at least 2 years ago, is not receiving active treatment and no more than 15 years may have elapsed between treatment with cranial-spinal radiation and time of the trial. Survivors with a shunt will be included in the trial, but will need to be identified prior to study enrollment to discuss any specific considerations for imaging.

  5. Meet criteria for adequate organ function requirements:

    1. Adequate renal function defined as: Creatinine clearance or radioisotope glomerular filtration rate (GFR) > 70ml/min/1.73 m2 or serum creatinine based on age/gender as follows:

      Maximum Serum Creatinine Level (mg/dL)

      5 to < 10 years: Male = 1; Female = 1

      10 to < 13 years: Male = 1.2; Female = 1.2

      13 to < 16 years: Male = 1.5; Female = 1.4

      ≥ 16 years: Male = 1.7; Female = 1.4

    2. Adequate liver function defined as:

    Total bilirubin < 1.5 x upper limit of normal (ULN) for age, and,

    serum glutamate oxaloacetate transaminase (SGOT) (AST) or serum glutamate pyruvate transaminase (SGPT) (ALT) < 3 x upper limit of normal (ULN) for age.

  6. Females of childbearing potential must have a negative pregnancy test result and must agree to use a medically acceptable method of contraception throughout the entire study period and for 30 days after the last dose of study drug.

  7. Informed consent will be obtained from the participants and/or their legal guardians by study team members authorized to consent for this study.

Exclusion criteria: Survivors will be excluded if they

  1. Are receiving palliative care.
  2. Are unable to participate in neuro-imaging without sedation as this is the primary outcome measure for the trial.
  3. Are unable to swallow tablets.
  4. Are unstable and/or insulin-dependent (Type 1) diabetic patients.
  5. Have acute or chronic metabolic acidosis and/or lactic acidosis.
  6. Any female patient or partner who has reached menarche and male patients who are not willing to use an effective method of contraception.
  7. Patient who is pregnant or lactating and does not agree to stop breastfeeding while receiving trial treatment.
  8. Have a history of renal disease or renal dysfunction e.g., as suggested by elevated serum creatinine levels (see 5.a. Inclusion criteria) or abnormal creatinine clearance.
  9. Have a history of congestive heart failure requiring pharmacologic treatment.
  10. Have a known hypersensitivity to metformin hydrochloride.

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Ontwerpdetails

  • Primair doel: Behandeling
  • Toewijzing: Gerandomiseerd
  • Interventioneel model: Crossover-opdracht
  • Masker: Verviervoudigen

Wapens en interventies

Deelnemersgroep / Arm
Interventie / Behandeling
Experimenteel: Group A (Crossover Group 1)

Subjects assigned to this arm will receive metformin first, followed by a washout period and then placebo.
Geneesmiddel: Metformin

Metformin doses will be 500 mg/m2 po daily given in 2 doses for one week and if there are no concerns increased to 1000 mg/m2 po daily given in 2 doses for the rest of the 12 week trial. The investigators will use the closest dose according to body surface area (250-500-750-1000) BID.

Geneesmiddel: Placebo

Placebo doses will be 500 mg/m2 po daily given in 2 doses for one week and if there are no concerns increased to 1000 mg/m2 po daily given in 2 doses for the rest of the 12 week trial. The investigators will use the closest dose according to body surface area (250-500-750-1000) BID.
Experimenteel: Group B (Crossover Group 2)

Subjects assigned to this arm will receive placebo first, followed by a washout period and then metformin.
Geneesmiddel: Metformin

Metformin doses will be 500 mg/m2 po daily given in 2 doses for one week and if there are no concerns increased to 1000 mg/m2 po daily given in 2 doses for the rest of the 12 week trial. The investigators will use the closest dose according to body surface area (250-500-750-1000) BID.

Geneesmiddel: Placebo

Placebo doses will be 500 mg/m2 po daily given in 2 doses for one week and if there are no concerns increased to 1000 mg/m2 po daily given in 2 doses for the rest of the 12 week trial. The investigators will use the closest dose according to body surface area (250-500-750-1000) BID.

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Feasibility: Medication Adherence
Tijdsspanne: Outcome 2 (Week 35)

Participant's adherence to taking study medication (Metformin or Placebo) as instructed based on dosing nomogram, for the whole study.

% Medication adherence = (Number of tablets actually consumed / Number of tablets expected to be consumed)*100

Number of tablets actually consumed is based on compliance counts conducted at the end of the study.
Outcome 2 (Week 35)
Safety: Frequency of Adverse Events (AE)
Tijdsspanne: Outcome 2 (Week 35)

The frequency of all AEs experienced during metformin and placebo treatment for all participants.
Outcome 2 (Week 35)

Secundaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Cognitive Testing: Declarative Memory - Change in Children's Auditory Verbal Learning Test -2 (CAVLT-2)
Tijdsspanne: Baseline 1 (Week 1), Outcome 1 (Week 13), Baseline 2 (Week 23), and Outcome 2 (Week 35)

For Arm AB:

  1. Change in Immediate Recall test from Baseline 1 (Week 1) at Outcome 1 (Week 13, post 12-week intervention)
  2. Change in Immediate Recall test from Baseline 2 (Week 23, post 10-week washout) at Outcome 2 (Week 35, post 2nd 12-week intervention)
  3. Change in Immediate Recall test from Baseline 1 (Week 1) at Outcome 2 (Week 35, post 2nd 12-week intervention)

For Arm BA:

  1. Change in Immediate Recall test from Baseline 1 (Week 1) at Outcome 1 (Week 13)
  2. Change in Immediate Recall test from Baseline 2 (Week 23) at Outcome 2 (Week 35)
  3. Change in Immediate Recall test from Baseline 1 (Week 1) at Outcome 2 (Week 35)
Baseline 1 (Week 1), Outcome 1 (Week 13), Baseline 2 (Week 23), and Outcome 2 (Week 35)
Cognitive Testing: Working Memory - Change in List Sort Working Memory Subtest of the NIH Toolbox Cognition Battery
Tijdsspanne: Baseline 1 (Week 1), Outcome 1 (Week 13), Baseline 2 (Week 23), Outcome 2 (Week 35)

For Arm AB:

  1. Change in List Sort Working Memory Test from Baseline 1 (Week 1) at Outcome 1 (Week 13)
  2. Change in List Sort Working Memory Test from Baseline 2 (Week 23) at Outcome 2 (Week 35)
  3. Change in List Sort Working Memory Test from Baseline 1 (Week 1) at Outcome 2 (Week 35)

For Arm BA:

  1. Change in List Sort Working Memory Test from Baseline 1 (Week 1) at Outcome 1 (Week 13)
  2. Change in List Sort Working Memory Test from Baseline 2 (Week 23) at Outcome 2 (Week 35)
  3. Change in List Sort Working Memory Test from Baseline 1 (Week 1) at Outcome 2 (Week 35)
Baseline 1 (Week 1), Outcome 1 (Week 13), Baseline 2 (Week 23), Outcome 2 (Week 35)
Cognitive Testing: Processing Speed - Change in Mean Reaction Time across Cambridge Neuropsychological Test Automated Battery (CANTAB) subtests
Tijdsspanne: Baseline 1 (Week 1), Outcome 1 (Week 13), Baseline 2 (Week 23), and Outcome 2 (Week 35)

Change in Mean Reaction Time (MRT) across the following CANTAB subtests:

  1. Rapid Visual Information Processing (RVP)
  2. Reaction Time (RT)
  3. Match to Sample Visual Search (MTS)
  4. Delayed Matching in 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.

For Arm AB:

  1. Change in MRT from Baseline 1 (Week 1) at Outcome 1 (Week 13)
  2. Change in MRT from Baseline 2 (Week 23) at Outcome 2 (Week 35)
  3. Change in MRT from Baseline 1 (Week 1) at Outcome 2 (Week 35)

For Arm BA:

  1. Change in MRT from Baseline 1 (Week 1) at Outcome 1 (Week 13)
  2. Change in MRT from Baseline 2 (Week 23) at Outcome 2 (Week 35)
  3. Change in MRT from Baseline 1 (Week 1) at Outcome 2 (Week 35)
Baseline 1 (Week 1), Outcome 1 (Week 13), Baseline 2 (Week 23), and Outcome 2 (Week 35)

Andere uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Neuroimaging: MRI Measures of White Matter Growth within the Corpus Callosum
Tijdsspanne: Baseline 1 (Week 1), Outcome 1 (Week 13), Baseline 2 (Week 23), and Outcome 2 (Week 35)

Change in Axonal Water Fraction (AWF)- Diffusion Kurtosis Imaging (DKI) metric sensitive to myelin
Baseline 1 (Week 1), Outcome 1 (Week 13), Baseline 2 (Week 23), and Outcome 2 (Week 35)
Neuroimaging: MRI Measures of Hippocampal Volume
Tijdsspanne: Baseline 1 (Week 1), Outcome 1 (Week 13), Baseline 2 (Week 23), and Outcome 2 (Week 35

Change in Hippocampal Volume, as measured by Cerebral Blood Flow (CBF)
Baseline 1 (Week 1), Outcome 1 (Week 13), Baseline 2 (Week 23), and Outcome 2 (Week 35

Medewerkers en onderzoekers

Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.

Sponsor

The Hospital for Sick Children

Onderzoekers

  • Hoofdonderzoeker: Donald Mabbott, PhD, The Hospital for Sick Children

Publicaties en nuttige links

De persoon die verantwoordelijk is voor het invoeren van informatie over het onderzoek stelt deze publicaties vrijwillig ter beschikking. Dit kan gaan over alles wat met het onderzoek te maken heeft.

Algemene publicaties

Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start (Werkelijk)

13 juni 2014

Primaire voltooiing (Werkelijk)

15 december 2017

Studie voltooiing (Werkelijk)

15 december 2017

Studieregistratiedata

Eerst ingediend

7 januari 2014

Eerst ingediend dat voldeed aan de QC-criteria

15 januari 2014

Eerst geplaatst (Geschat)

20 januari 2014

Updates van studierecords

Laatste update geplaatst (Werkelijk)

24 september 2026

Laatste update ingediend die voldeed aan QC-criteria

21 september 2026

Laatst geverifieerd

1 september 2026

Meer informatie

Termen gerelateerd aan deze studie

Trefwoorden

Aanvullende relevante MeSH-voorwaarden

Andere studie-ID-nummers

  • 1000039383

Plan Individuele Deelnemersgegevens (IPD)

Bent u van plan om gegevens van individuele deelnemers (IPD) te delen?

NEE

Informatie over medicijnen en apparaten, studiedocumenten

Bestudeert een door de Amerikaanse FDA gereguleerd geneesmiddel

Nee

Bestudeert een door de Amerikaanse FDA gereguleerd apparaatproduct

Nee

Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .

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