PhD Study : Development of a pharmacogenomic model to predict efficacy or adverse events to cannabidiol treatment of arthritic pain.

Apply and key information  

Summary

The endogenous cannabinoid system modulates neuronal and immune cell function, both of which play key roles in Osteoarthritis (OA) and rheumatoid arthritis (RA) pain. Cannabidiol (CBD) is a non-psychoactive compound extracted from cannabis. CBD binding of endogenous receptors can produce reliable anti-nociceptive effects in preclinical inflammatory and neuropathic pain models. However cannabidiol’s safety and efficacy have not yet been studied independently by clinical trial for pain in arthritis. The ESCAPe (CHITIN) study proposed would be the first of its kind to investigate the safety profile and pain effects of CBD, in these conditions. CBD is metabolized in the liver by cytochrome P450 enzymes CYP2C and CYP3A converting it into 7-OH-CBD and 6-OH-CBD.

Of particular relevance to safety, CBD has potential to block cytochrome P450 metabolism of other co-medications in the liver, such as NSAID and opioid co-medications in arthritis patients. Therefore pharmacogenomic and pharmacokinetic studies will be conducted in parallel, to identify variants of cannabidiol metabolising enzymes and receptors which in combination could be carried by individuals more likely to respond or at higher risk of adverse events.

Aim: Discover genomic variant data that to stratify patients achieving pain reduction or at risk of adverse events, when treated with cannabidiol.

Objectives:

1. Perform pharmacokinetic analysis of CBD, NSAID and opioid metabolites in patients to measure any changes in metabolism attributable to CBD.

2. Data from a pharmacogenomic screen of CBD metabolising enzymes will be analysed for associations with CBD reduction in pain scores or adverse events.

Methods:

a)Genomic analyses: DNA will be extracted from whole blood samples and targeted gene sequencing and variant calling will performed using TruSeq custom amplicon kits and an Illumina MiSeq instrument at NI Centre for Stratified Medicine (NICSM).  Analysis of single nucleotide polymorphisms (SNPs) with functional consequences for CBD metabolism or signalling will be focussed on CYP2C19 and CYP3A4 genes. The strength of associations between individual SNPs and drug levels or pain response scores will be assessed by multivariate regression modelling.

b)Pharmacokinetics: the metabolism of CBD and its metabolites will be analysed in blood plasma and urine samples for both Stage 1 and 2 studies. Samples will be centrifuged to remove cellular material and frozen at the recruitment site, sent to NICSM for analyses at the Mass Spectrometry Core Technology Unit at Ulster University. CBD, 7-OH-CBD and 6-OH-CBD, NSAID and opioid plasma and urine concentrations will be ascertained by a liquid extraction surface analysis (LESA)-nano electrospray ionisation triple quadrupole mass spectrometry method (ESI-QQQ MS) using.

c)Bioinformatic analyses:  Statistical analysis will be performed by SPSS (version 24.0). Pre- and post-treatment outcome data will be will be analysed to examine any relationships between the specific genotype/drug meatbolite profile of a patient with their disease activity, demographics and clinically determined response to therapy. A patient stratification algorithm and model will be designed to detect associations between specific gene variants CBD pain response or adverse event.

Essential criteria

Applicants should hold, or expect to obtain, a First or Upper Second Class Honours Degree in a subject relevant to the proposed area of study.

We may also consider applications from those who hold equivalent qualifications, for example, a Lower Second Class Honours Degree plus a Master’s Degree with Distinction.

In exceptional circumstances, the University may consider a portfolio of evidence from applicants who have appropriate professional experience which is equivalent to the learning outcomes of an Honours degree in lieu of academic qualifications.

  • Sound understanding of subject area as evidenced by a comprehensive research proposal
  • A comprehensive and articulate personal statement

Desirable Criteria

If the University receives a large number of applicants for the project, the following desirable criteria may be applied to shortlist applicants for interview.

  • First Class Honours (1st) Degree
  • Masters at 65%
  • Completion of Masters at a level equivalent to commendation or distinction at Ulster
  • Research project completion within taught Masters degree or MRES
  • Experience using research methods or other approaches relevant to the subject domain
  • Work experience relevant to the proposed project
  • Publications - peer-reviewed
  • Experience of presentation of research findings

Funding and eligibility

The University offers the following levels of support:

Vice Chancellors Research Studentship (VCRS)

The following scholarship options are available to applicants worldwide:

  • Full Award: (full-time tuition fees + £19,000 (tbc))
  • Part Award: (full-time tuition fees + £9,500)
  • Fees Only Award: (full-time tuition fees)

These scholarships will cover full-time PhD tuition fees for three years (subject to satisfactory academic performance) and will provide a £900 per annum research training support grant (RTSG) to help support the PhD researcher.

Applicants who already hold a doctoral degree or who have been registered on a programme of research leading to the award of a doctoral degree on a full-time basis for more than one year (or part-time equivalent) are NOT eligible to apply for an award.

Please note: you will automatically be entered into the competition for the Full Award, unless you state otherwise in your application.

Department for the Economy (DFE)

The scholarship will cover tuition fees at the Home rate and a maintenance allowance of £19,000 (tbc) per annum for three years (subject to satisfactory academic performance).

This scholarship also comes with £900 per annum for three years as a research training support grant (RTSG) allocation to help support the PhD researcher.

  • Candidates with pre-settled or settled status under the EU Settlement Scheme, who also satisfy a three year residency requirement in the UK prior to the start of the course for which a Studentship is held MAY receive a Studentship covering fees and maintenance.
  • Republic of Ireland (ROI) nationals who satisfy three years’ residency in the UK prior to the start of the course MAY receive a Studentship covering fees and maintenance (ROI nationals don’t need to have pre-settled or settled status under the EU Settlement Scheme to qualify).
  • Other non-ROI EU applicants are ‘International’ are not eligible for this source of funding.
  • Applicants who already hold a doctoral degree or who have been registered on a programme of research leading to the award of a doctoral degree on a full-time basis for more than one year (or part-time equivalent) are NOT eligible to apply for an award.

Due consideration should be given to financing your studies. Further information on cost of living

The Doctoral College at Ulster University

Key dates

Submission deadline
Monday 19 February 2018
12:00AM

Interview Date
6, 7 and 8 March 2018

Preferred student start date
Mid September 2018

Applying

Apply Online  

Contact supervisor

Dr David Gibson

Other supervisors