Brain Tumor Treated With Cranial or Cranial-Spinal Radiation Clinical Trial
Official title:
Placebo Controlled Double Blind Crossover Trial of Metformin for Brain Repair in Children With Cranial-Spinal Radiation for Medulloblastoma
| Verified date | June 2024 |
| Source | The Hospital for Sick Children |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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.
| Status | Completed |
| Enrollment | 24 |
| Est. completion date | December 15, 2017 |
| Est. primary completion date | December 15, 2017 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 5 Years to 21 Years |
| Eligibility | 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. |
| Country | Name | City | State |
|---|---|---|---|
| Canada | The Hospital for Sick Children | Toronto | Ontario |
| Lead Sponsor | Collaborator |
|---|---|
| The Hospital for Sick Children |
Canada,
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 — View Citation
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Other | Neuroimaging: MRI Measures of White Matter Growth within the Corpus Callosum | 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) | |
| Other | Neuroimaging: MRI Measures of Hippocampal Volume | 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 | |
| Primary | 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. |
Outcome 2 (Week 35) | |
| Primary | Safety: Frequency of Adverse Events (AE) | The frequency of all AEs experienced during metformin and placebo treatment for all participants. | Outcome 2 (Week 35) | |
| Secondary | Cognitive Testing: Declarative Memory - Change in Children's Auditory Verbal Learning Test -2 (CAVLT-2) | For Arm AB:
Change in Immediate Recall test from Baseline 1 (Week 1) at Outcome 1 (Week 13, post 12-week intervention) Change in Immediate Recall test from Baseline 2 (Week 23, post 10-week washout) at Outcome 2 (Week 35, post 2nd 12-week intervention) Change in Immediate Recall test from Baseline 1 (Week 1) at Outcome 2 (Week 35, post 2nd 12-week intervention) For Arm BA: Change in Immediate Recall test from Baseline 1 (Week 1) at Outcome 1 (Week 13) Change in Immediate Recall test from Baseline 2 (Week 23) at Outcome 2 (Week 35) 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) | |
| Secondary | Cognitive Testing: Working Memory - Change in List Sort Working Memory Subtest of the NIH Toolbox Cognition Battery | For Arm AB:
Change in List Sort Working Memory Test from Baseline 1 (Week 1) at Outcome 1 (Week 13) Change in List Sort Working Memory Test from Baseline 2 (Week 23) at Outcome 2 (Week 35) Change in List Sort Working Memory Test from Baseline 1 (Week 1) at Outcome 2 (Week 35) For Arm BA: Change in List Sort Working Memory Test from Baseline 1 (Week 1) at Outcome 1 (Week 13) Change in List Sort Working Memory Test from Baseline 2 (Week 23) at Outcome 2 (Week 35) 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) | |
| Secondary | 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:
Rapid Visual Information Processing (RVP) Reaction Time (RT) Match to Sample Visual Search (MTS) 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: Change in MRT from Baseline 1 (Week 1) at Outcome 1 (Week 13) Change in MRT from Baseline 2 (Week 23) at Outcome 2 (Week 35) Change in MRT from Baseline 1 (Week 1) at Outcome 2 (Week 35) For Arm BA: Change in MRT from Baseline 1 (Week 1) at Outcome 1 (Week 13) Change in MRT from Baseline 2 (Week 23) at Outcome 2 (Week 35) 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) |