Understanding the impact of the routine use of anti-diabetic (PPAR gamma)/anti-hyperlipidaemic (PPAR alpha) medication on risk of brain tumours and case fatality

Date of ISAC Approval: 
24/07/2018
Lay Summary: 
This project aims to test whether some drugs which are currently used for treating patients with diabetes and high blood fats (e.g. cholesterol) (known as glitazones and fibrates), may reduce the risk of developing primary or secondary brain tumours and/or slow the rate of disease progression and death. If our results are positive this would suggest these drugs could be used in patients with brain tumours or at high risk of developing tumours. Stronger evidence would be required, for example by doing a clinical trial, before they could be used in routine health care.
Technical Summary: 
Brain cancer (primary and secondary brain cancer) has an extremely poor overall survival with less than 3% patients alive after 5 years. There has been interesting preliminary evidence suggesting that diabetic patients receiving peroxisome proliferator-activated receptor gamma (PPAR gamma) agonists, a group of anti-diabetic, thiazolidinedione drugs, have an increased median survival for primary brain cancer glioblastoma. Another study has shown that glioblastoma brain cancer patients with a high level of PPAR alpha gene expression have an improved overall survival. However, at present, no clinical trials are under-way with regards to treating glioma patients using PPAR gamma or PPAR alpha agonists. This study aims to evaluate the potential of PPAR gamma and PPAR alpha agonists in prevention and as novel neoadjuvants in the treatment (tertiary prevention) of brain cancer. We will conduct 2 nested case-control studies to investigate, using multivariable logistic regression, whether the exposure to PPAR gamma or PPAR alpha agonist has an effect on diagnosis of brain cancer. A clinical cohort study will use multivariable proportional hazard models to determine whether exposure to these medication is associated with reduced case fatality.
Health Outcomes to be Measured: 
- Brain tumour (primary and secondary) - Death
Collaborators: 

Professor Yoav Ben-Shlomo - Chief Investigator - University of Bristol
Kathreena Kurian - Collaborator - University of Bristol
Mio Ozawa - Collaborator - University of Bristol
Professor Richard Martin - Collaborator - University of Bristol
Dr Theresa Redaniel - Collaborator - University of Bristol
Professor Yoav Ben-Shlomo - Corresponding Applicant - University of Bristol

Linkages: 
ONS;Patient IMD