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Imaging pain relief in osteoarthritis (IPRO): protocol of a double-blind randomised controlled mechanistic study assessing pain relief and prediction of duloxetine treatment outcome
  1. Diane Reckziegel1,2,3,
  2. Helen Bailey1,2,3,
  3. William J Cottam1,2,3,
  4. Christopher R Tench4,
  5. Ravi P Mahajan1,5,
  6. David A Walsh1,6,
  7. Roger D Knaggs1,7,
  8. Dorothee P Auer1,2,3
  1. 1 Arthritis Research UK Pain Centre, University of Nottingham, Nottingham, UK
  2. 2 Sir Peter Mansfield Imaging Centre, University of Nottingham, Nottingham, UK
  3. 3 Division of Clinical Neuroscience, Radiological Sciences, University of Nottingham, Nottingham, UK
  4. 4 Division of Clinical Neuroscience, Clinical Neurology, University of Nottingham, Nottingham, UK
  5. 5 Division of Clinical Neuroscience, Anaesthesia and Critical Care, University of Nottingham, Nottingham, UK
  6. 6 Division of Rheumatology, Orthopaedics and Dermatology, University of Nottingham, Nottingham, UK
  7. 7 School of Pharmacy, University of Nottingham, Nottingham, UK
  1. Correspondence to Professor Dorothee P Auer; dorothee.auer{at}nottingham.ac.uk

Abstract

Introduction Osteoarthritis (OA) pain is a major cause of long-term disability and chronic pain in the adult population. One in five patients does not receive satisfactory pain relief, which reflects the complexity of chronic pain and the current lack of understanding of mechanisms of chronic pain. Recently, duloxetine has demonstrated clinically relevant pain relief, but only in half of treated patients with OA. Here, the aim is to investigate the neural mechanisms of pain relief and neural signatures that may predict treatment response to duloxetine in chronic knee OA pain.

Methods and analysis This is an ongoing single-centre randomised placebo-controlled mechanistic study (2:1 (placebo) allocation), using a multimodal neuroimaging approach, together with psychophysiological (quantitative sensory testing), genetics and questionnaire assessments. Eighty-one subjects with chronic knee OA pain are planned to power for between-group comparisons (placebo, duloxetine responder and duloxetine non-responder). Participants have a baseline assessment and, following 6 weeks of duloxetine (30 mg for 2 weeks, then 60 mg for 4 weeks), a follow-up evaluation. Brain imaging is performed at 3T with blood-oxygen-level dependent functional MRI at rest and during pin-prick nociceptive stimulation for main outcome assessment; arterial spin labelling and structural imaging (T1-weighted) for secondary outcome assessment. Questionnaires evaluate pain, negative affect, quality of sleep and cognition.

Ethics and dissemination The study has been approved by the East Midlands, Nottingham and is being carried out under the principles of the Declaration of Helsinki (64th, 2013) and Good Clinical Practice standards. Results will be disseminated in peer-reviewed journals and at scientific conferences.

Trial registration number This trial is registered at ClinicalTrials.gov (NCT02208778).

This work was supported by Arthritis Research UK (Grant 18769).

  • Osteoarthritis pain
  • magnetic resonance imaging
  • fMRI
  • analgesia
  • duloxetine
  • antidepressant

This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: http://creativecommons.org/licenses/by/4.0/

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Footnotes

  • Contributors DPA and DAW designed the study and DR, DPA, RDK, CRT and RPM developed the research protocol. DR leads the study, is responsible for data acquisition and will conduct image and statistical analyses. CRT provides statistical consultation. DR, HB and WC undertake recruitment and data collection. DR and DPA wrote the manuscript, which was edited by CRT and RDK. All authors approved the final manuscript.

  • Competing interests None declared.

  • Patient consent Detail has been removed from this case description/these case descriptions to ensure anonymity. The editors and reviewers have seen the detailed information available and are satisfied that the information backs up the case the authors are making.

  • Ethics approval East Midlands—Nottingham 2 research ethics committee.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Correction notice This paper has been amended since it was published Online First. Owing to a scripting error, some of the publisher names in the references were replaced with 'BMJ Publishing Group'. This only affected the full text version, not the PDF. We have since corrected these errors and the correct publishers have been inserted into the references.

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