AzTrials
AzTrials

Brain Tumor Treated With Cranial or Cranial-Spinal RadiationPhase 3NCT02040376

Metformin for Brain Repair in Children With Cranial-Spinal Radiation for Medulloblastoma

A Phase 3 study testing Metformin in people with Brain Tumor Treated With Cranial or Cranial-Spinal Radiation, run by The Hospital for Sick Children at 1 site in Canada.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

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… Read more about this study

Who is it for?
Ages 5 to 21 years
What is being tested?
Metformin
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
24 participants
Where
1 siteCanada
Study dates
13 Jun 2014to 15 Dec 2017
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 5 to 21 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • Have been treated with cranial or cranial-spinal radiation,
  • Are between 5 and 21 years of age at time of consent, and
  • 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.
  • 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.
  • Meet criteria for adequate organ function requirements:
  • 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:
Show all 16Show fewer
  • 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
  • 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.
  • 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.
  • Informed consent will be obtained from the participants and/or their legal guardians by study team members authorized to consent for this study.

Who cannot join

  • Are receiving palliative care.
  • Are unable to participate in neuro-imaging without sedation as this is the primary outcome measure for the trial.
  • Are unable to swallow tablets.
  • Are unstable and/or insulin-dependent (Type 1) diabetic patients.
  • Have acute or chronic metabolic acidosis and/or lactic acidosis.
  • Any female patient or partner who has reached menarche and male patients who are not willing to use an effective method of contraception.
Show all 10Show fewer
  • Patient who is pregnant or lactating and does not agree to stop breastfeeding while receiving trial treatment.
  • 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.
  • Have a history of congestive heart failure requiring pharmacologic treatment.
  • Have a known hypersensitivity to metformin hydrochloride.

Trial locations and contacts

1 site in 1 country.

Canada1 site

  • The Hospital for Sick Children

    Toronto, Ontario, M5G 1X8

Other trials in Canada

About this study

Official title: Placebo Controlled Double Blind Crossover Trial of Metformin for Brain Repair in Children With Cranial-Spinal Radiation for Medulloblastoma

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.

Read the detailed description

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).

Being tested
Metformin, Placebo
Keywords
Paediatrics, Medulloblastoma, Metformin
Medical subject headings
Medulloblastoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MetforminDrug

    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.

  • PlaceboDrug

    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.

Study groups in NCT02040376
Study groupRoleWhat they receive
Group A (Crossover Group 1)ExperimentalSubjects assigned to this arm will receive metformin first, followed by a washout period and then placebo.
Receives: Drug: Metformin; Drug: Placebo
Group B (Crossover Group 2)ExperimentalSubjects assigned to this arm will receive placebo first, followed by a washout period and then metformin.
Receives: Drug: Metformin; Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Feasibility: Medication Adherence

    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.

    Measured: Outcome 2 (Week 35)

  2. Safety: Frequency of Adverse Events (AE)

    The frequency of all AEs experienced during metformin and placebo treatment for all participants.

    Measured: Outcome 2 (Week 35)

Secondary outcomes (3)

  1. Cognitive Testing: Declarative Memory - Change in Children's Auditory Verbal Learning Test -2 (CAVLT-2)

    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)

    Measured: Baseline 1 (Week 1), Outcome 1 (Week 13), Baseline 2 (Week 23), and Outcome 2 (Week 35)

  2. Cognitive Testing: Working Memory - Change in List Sort Working Memory Subtest of the NIH Toolbox Cognition Battery

    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)

    Measured: Baseline 1 (Week 1), Outcome 1 (Week 13), Baseline 2 (Week 23), Outcome 2 (Week 35)

  3. Cognitive Testing: Processing Speed - Change in Mean Reaction Time across Cambridge Neuropsychological Test Automated Battery (CANTAB) subtests

    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)

    Measured: Baseline 1 (Week 1), Outcome 1 (Week 13), Baseline 2 (Week 23), and Outcome 2 (Week 35)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Jan 2014 (estimated)
  2. Study start13 Jun 2014
  3. Primary completion15 Dec 2017
  4. Study completion15 Dec 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Crossover
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
24 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02040376
Sponsor's protocol ID
1000039383
Status last verified
Sep 2026
First submitted
7 Jan 2014
Last updated
24 Sep 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Ayoub R, Ruddy RM, Cox E, Oyefiade A, Derkach D, Laughlin S, Ades-Aron B, Shirzadi Z, Fieremans E, MacIntosh BJ, de Medeiros CB, Skocic J, Bouffet E, Miller FD, Morshead CM, Mabbott DJ. Assessment of cognitive and neural recovery in survivors of pediatric brain tumors in a pilot clinical trial using metformin. Nat Med. 2020 Aug;26(8):1285-1294. doi: 10.1038/s41591-020-0985-2. Epub 2020 Jul 27.

    PubMed 32719487

  • Baudou E, Ryan JL, Tseng J, Bouffet E, Bartels U, Timmons BW, de Medeiros CB, Mabbott DJ. Repairing Myelin After Irradiated Pediatric Brain Tumor: A Magnetization Transfer Imaging Analysis. Pediatr Blood Cancer. 2025 Sep;72(9):e31838. doi: 10.1002/pbc.31838. Epub 2025 Jun 14.

    PubMed 40515500

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Metformin in people with Brain Tumor Treated With Cranial or Cranial-Spinal Radiation, run by The Hospital for Sick Children at 1 site in Canada.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 24 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Feasibility: Medication Adherence (time frame: Outcome 2 (Week 35)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02040376, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Sep 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in