The Role of Tryptophan Metabolism in the Development of Delirium v01

  • Research type

    Research Study

  • Full title

    Investigation into the Role of Tryptophan Metabolism in the Development of Delirium Symptoms

  • IRAS ID

    180962

  • Contact name

    Martyn Lloyd Stones

  • Contact email

    stonesml@cardiff.ac.uk

  • Sponsor organisation

    Cardiff University

  • Clinicaltrials.gov Identifier

    SPON 1430-15, Sponsor/Cardiff University reference number; 15/MEH/6212, Cardiff and Vale UHB R+D refernce number

  • Duration of Study in the UK

    0 years, 8 months, 1 days

  • Research summary

    Investigation into the role of tryptophan metabolism in the development of delirium symptoms following cardiac surgery.

    Delirium is a distressing condition affecting 35% of patients following heart surgery. Symptoms include fluctuating attention, confusion, and when severe, visual hallucinations and paranoid thoughts. Older patients are vulnerable to mental decline. Neither laboratory tests nor specifically tested medicines exist for delirium management. NICE (National Institute for Health and Care Excellence) has highlighted this as a research priority.

    Recent research has confirmed that elevated levels of inflammatory markers and the stress hormone cortisol are associated with delirium following surgery. Several small studies have demonstrated that levels of the amino acid tryptophan(needed for brain function) are low. This has led to trials giving surgical patients extra tryptophan. This did not prevent delirium, but interestingly, despite supplementation, the levels remained lower in those developing the disorder. This is probably due to diversion into alternative activated biochemical pathways.

    Psychiatric research has identified tryptophan related pathways, affected by stress and inflammation that can alter cognition, visual perception, and behaviour – key symptoms of delirium. We intend to explore the association of these pathways with the development and severity of delirium symptoms. Initial focus will investigate activation of the kynurenine and N,N-dimethyltryptamine producing pathways.

    Participants in the study will be patients with a planned heart operation at the University Hospital of Wales, Cardiff. We intend to recruit 100 patients who develop delirium and a comparison group of 100 patients without delirium. This is an observational study as we cannot predict who will develop delirium in advance. Urine and blood samples will be collected before and twice following surgery.

    This study will improve understanding of the mechanisms underlying delirium, a key step in the development of diagnostic tests and identification of medications for clinical evaluation in the disorder. Funding is provided by Cardiff University.

  • REC name

    Wales REC 1

  • REC reference

    16/WA/0348

  • Date of REC Opinion

    3 Jan 2017

  • REC opinion

    Further Information Favourable Opinion