Trial reportNature medicine2020
Assessment of cognitive and neural recovery in survivors of pediatric brain tumors in a pilot clinical trial using metformin.
Trial report in Nature medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 5 registered trials, which are not on this map. Cited by 69 papers, 4 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Placebo Controlled Double Blind Crossover Trial of Metformin for Brain Repair in Children With Cranial-Spinal Radiation for Medulloblastoma
Drug Repurposing Using Metformin for Improving the Therapeutic Outcome in Multiple Sclerosis Patients
Theophylline Prophylaxis During Hypothermia to Limit Neonatal Nephron Damage
Systemic Biomarkers to Predict Radiation-Induced Neurocognitive Decline in Pediatric and Young Adults With Primary Brain Tumors (BIO-RIN)
A Phase 0/Phase 1 Trial of Metformin for Premature Infants With Bronchopulmonary Dysplasia
Who cites it
69 citing papers in PubMed, 4 syntheses or guidelines pooled it, 119 citations in OpenAlex.
- Metformin for neurocognitive dysfunction in schizophrenia: a systematic review.Frontiers in psychiatry · 2024Pooled it
- Interventions for preventing and ameliorating cognitive deficits in adults treated with cranial irradiation.The Cochrane database of systematic reviews · 2022Pooled it
- Effect of metformin on adverse outcomes in T2DM patients: Systemic review and meta-analysis of observational studies.Frontiers in cardiovascular medicine · 2022Pooled it
- The effect of metformin on ameliorating neurological function deficits and tissue damage in rats following spinal cord injury: A systematic review and network meta-analysis.Frontiers in neuroscience · 2022Pooled it
- Memantine to preserve memory and neurocognition following craniospinal irradiation (MEMENTO): a phase 3 randomized controlled trial.BMC cancer · 2026Trial
- Metformin improves cognitive impairment in patients with schizophrenia: associated with enhanced functional connectivity of dorsolateral prefrontal cortex.Translational psychiatry · 2023Trial
- Radiomitigators: Breakthroughs in Post-Radiation Recovery.Antioxidants (Basel, Switzerland) · 2026Review
- Social information processing in survivors of pediatric brain tumors.Journal of cancer survivorship : research and practice · 2026Article
- Radiation-Induced Neurodegeneration.Biomedicines · 2026Review
- Article
- Metformin Alleviates Cognitive Impairment in Chronic-Phase Epileptic Rats by Modulating the TLR4/MyD88/NF-κB Pathway and Gut Flora Composition.Molecular neurobiology · 2025Article
- Neuropsychological function in childhood cancer patients and adult survivors of childhood cancer.Journal of clinical and experimental neuropsychology · 2025Review
- Repurposing Metformin in Precision Oncology: Mechanistic Insights, Biomarker-Guided Strategies, and Translational Imperatives.Medicina (Kaunas, Lithuania) · 2025Review
- Safety and feasibility trial protocol of metformin in infants after perinatal brain injury.BMJ paediatrics open · 2025Article
- Serum metabolic profiling enables diagnosis, prognosis, and monitoring for brainstem gliomas.Nature communications · 2025Article
- Tumor-infiltrating nerves: unraveling the role of cancer neuroscience in tumorigenesis, disease progression, and emerging therapies.Discover oncology · 2025Review
- Brains in space: impact of microgravity and cosmic radiation on the CNS during space exploration.Nature reviews. Neuroscience · 2025Review
- Metabolic stress-mediated cell death and autophagy in human lung cancer cells.The Journal of pharmacology and experimental therapeutics · 2025Article
- Approaches to Reduce Toxicity in Pediatric Brain Tumors.Current oncology (Toronto, Ont.) · 2025Review
- The National Cancer Institute clinical trials planning meeting to address gaps in observational and intervention trials for cancer-related cognitive impairment.Journal of the National Cancer Institute · 2025Article
9 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 4 institutions in 2 countries.
Funding
Abstract
We asked whether pharmacological stimulation of endogenous neural precursor cells (NPCs) may promote cognitive recovery and brain repair, focusing on the drug metformin, in parallel rodent and human studies of radiation injury. In the rodent cranial radiation model, we found that metformin enhanced the recovery of NPCs in the dentate gyrus, with sex-dependent effects on neurogenesis and cognition. A pilot double-blind, placebo-controlled crossover trial was conducted (ClinicalTrials.gov, NCT02040376) in survivors of pediatric brain tumors who had been treated with cranial radiation. Safety, feasibility, cognitive tests and MRI measures of white matter and the hippocampus were evaluated as endpoints. Twenty-four participants consented and were randomly assigned to complete 12-week cycles of metformin (A) and placebo (B) in either an AB or BA sequence with a 10-week washout period at crossover. Blood draws were conducted to monitor safety. Feasibility was assessed as recruitment rate, medication adherence and procedural adherence. Linear mixed modeling was used to examine cognitive and MRI outcomes as a function of cycle, sequence and treatment. We found no clinically relevant safety concerns and no serious adverse events associated with metformin. Sequence effects were observed for all cognitive outcomes in our linear mixed models. For the subset of participants with complete data in cycle 1, metformin was associated with better performance than placebo on tests of declarative and working memory. We present evidence that a clinical trial examining the effects of metformin on cognition and brain structure is feasible in long-term survivors of pediatric brain tumors and that metformin is safe to use and tolerable in this population. This pilot trial was not intended to test the efficacy of metformin for cognitive recovery and brain growth, but the preliminary results are encouraging and warrant further investigation in a large multicenter phase 3 trial.
Indexed as
Identifiers
What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.