Evidence map›Paper›PMID 33681737›Full record

ArticleEClinicalMedicine2021

The metformin in tuberous sclerosis (MiTS) study: A randomised double-blind placebo-controlled trial.

Sam Amin, Andrew A Mallick, Hannah Edwards, Mario Cortina-Borja, Matthew Laugharne, Marcus Likeman, Finbar J K O'Callaghan

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in EClinicalMedicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
2.6field-weighted citation impact, top 10% of its field
1 · What the graph read from 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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

23 citing papers in PubMed, 30 citations in OpenAlex.

  1. Trial
  2. Trial
  3. Article
  4. Article
  5. Article
  6. Review
  7. Article
  8. Review
  9. Review
  10. Review
  11. Review
  12. Review
  13. Review
  14. Article
  15. Review
  16. Review
  17. Review
  18. Review
  19. Review
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 4 institutions in 1 country.

Sam AminClinical Neurosciences Section, Room 41, 4th Floor PUW South, UCL Great Ormond Street Institute of Child Health, University College London, London WC1N 1EH, United Kingdom.
Andrew A MallickDepartment of Paediatric Neurology, Bristol Royal Hospital for Children, Upper Maudlin Street, Bristol BS3 8AE, United Kingdom.
Hannah EdwardsPopulation Health Sciences, Bristol Medical School, University of Bristol, United Kingdom.
Mario Cortina-BorjaPopulation, Policy and Practice Teaching and Research Department, Great Ormond Street Institute of Child Health, University College London, London, United Kingdom.
Matthew LaugharneRadiology Department, Royal United Hospitals Bath NHS Foundation Trust, Combe Park, Bath BA1 3NG, United Kingdom.
Marcus LikemanDepartment of Paediatric Radiology, Bristol Royal Hospital for Children, Upper Maudlin Street, Bristol BS3 8AE, United Kingdom.
Finbar J K O'CallaghanClinical Neurosciences Section, Room 41, 4th Floor PUW South, UCL Great Ormond Street Institute of Child Health, University College London, London WC1N 1EH, United Kingdom.
Bristol Royal Hospital for Children · GBGreat Ormond Street Hospital · GBRoyal United Hospital Bath NHS Trust · GBUniversity of Bristol · GB

Funding

Department of Health PB-PG-0909-20131
6 · The paper itself

Abstract

backgroundTuberous Sclerosis Complex (TSC) is a genetic disorder characterised by the development of benign tumours secondary to loss of inhibitory regulation of the mTOR (mechanistic Target of Rapamycin) intracellular growth pathway. Metformin inhibits the mTOR pathway. We investigated whether metformin would reduce growth of hamartomas associated with tuberous sclerosis complex.

methodsIn this multicentre randomized, double-blind, placebo-controlled trial, patients with a clinical diagnosis of tuberous sclerosis, aged over 10 years and with at least one renal angiomyolipoma of greater than 1 cm in diameter were enrolled. Participants were randomly allocated (1:1) by a secure website to receive metformin or placebo for 12 months. The primary outcome was percentage volume change of renal angiomyolipomas (AML) at 12 months compared to baseline. Secondary outcomes were percentage change at 12 months from baseline in volume of cerebral Subependymal Giant Cell Astrocytomas (SEGA); appearance of facial and ungual hamartomas; frequency of epileptic seizures; and adaptive behaviour. The trial is registered with The International Standard Randomised Controlled Trial Number (ISRCTN), number 92545532, and the European Union Drug Regulating Authorities Clinical Trials (EUDRACT), number 2011-001319-30.

findingsBetween 1 November 2012 and 30 September 2015 72 patients were screened and 55 were randomly assigned to metformin (28) or placebo (27). Four participants withdrew between randomisation and starting treatment. All 51 patients who started therapy completed the trial and were assessed for outcome at 12 months. The median percentage change in angiomyolipoma (AML) volume was +7.6% (IQR -1.8% to +42.6%) for the placebo group and +8.9% (IQR 1.3% to 19.5%) for the metformin group (

interpretationMetformin did not reduce AML volume. Metformin did reduce SEGA volume and seizure frequency compared with placebo. There may be a role for metformin in slowing or reversing growth of some life-threatening hamartomas in TSC and for reducing seizure frequency. Further study is justified.

fundingThis study was funded by the National Institute for Health and Research (NIHR) through the The Research for Patient Benefit Programme (RfPB).

Identifiers

PMID33681737
PMCPMC7910694
OpenAlexW3120794794

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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 OpenQuestion graph.