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Efficacy and safety of cannabidiol followed by an open label add-on of tetrahydrocannabinol for the treatment of chronic pain in patients with rheumatoid arthritis or ankylosing spondylitis: protocol for a multicentre, randomised, placebo-controlled study
  1. Oliver Hendricks1,2,
  2. Tonny Elmose Andersen3,
  3. Afshin Ashouri Christiansen1,2,
  4. Jette Primdahl1,4,
  5. Ellen Margrethe Hauge5,
  6. Torkell Ellingsen6,
  7. Tina Ingrid Horsted1,
  8. Anja Godske Bachmann1,2,
  9. Anne Gitte Loft5,
  10. Anders Bo Bojesen1,
  11. Mikkel Østergaard7,8,
  12. Merete Lund Hetland7,8,
  13. Niels Steen Krogh7,
  14. Kirsten Kaya Roessler3,
  15. Kim Hørslev Petersen1,2
  1. 1 Rheumatology, Danish Hospital for Rheumatic Diseases, Gråsten, Denmark
  2. 2 IRS, Syddansk Universitet Det Naturvidenskabelige Fakultet, Odense, Denmark
  3. 3 Department of Psychology, Syddansk Universitet Det Sundhedsvidenskabelige Fakultet, Odense, Denmark
  4. 4 Department of Regional Health Research, Syddansk Universitet Det Sundhedsvidenskabelige Fakultet, Odense, Denmark
  5. 5 Department of Rheumatology, Aarhus Universitet Health, Aarhus, Denmark
  6. 6 Rheumatology, Odense University Hospital, Odense, Denmark
  7. 7 Department of Rheumatology, COPECARE, Rigshospitalet Glostrup, Glostrup, Denmark
  8. 8 Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
  1. Correspondence to Dr Oliver Hendricks; hendricks{at}dadlnet.dk

Abstract

Introduction Rheumatoid arthritis (RA) and ankylosing spondylitis (AS) are chronic, systemic, inflammatory diseases, primarily in the musculoskeletal system. Pain and fatigue are key symptoms of RA and AS. Treatment presents a clinical challenge for several reasons, including the progressive nature of the diseases and the involvement of multiple pain mechanisms. Moreover, side effects of pain treatment pose an implicit risk. Currently, no well-controlled studies have investigated how medical cannabis affects pain and cognitive functions in RA and AS. The present study aims to evaluate the efficacy and safety of medical cannabis in the treatment of persistent pain in patients with RA and AS with low disease activity.

Methods and analysis A double-blinded, randomised, placebo-controlled study of cannabidiol (CBD), followed by an open label add-on of tetrahydrocannabinol (THC) with collection of clinical data and biological materials in RA and AS patients treated in routine care. The oral treatment with CBD in the experimental group is compared with placebo in a control group for 12 weeks, followed by an observational 12-week period with an open label add-on of THC in the primary CBD non-responders. Disease characteristics, psychological parameters, demographics, comorbidities, lifestyle factors, blood samples and serious adverse events are collected at baseline, after 12 and 24 weeks of treatment, and at a follow-up visit at 36 weeks. Data will be analysed in accordance with a predefined statistical analysis plan.

Ethics and dissemination The Danish Ethics Committee (S-20170217), the Danish Medicines Agency (S-2018010018) and the Danish Data Protection Agency approved the protocol. The project is registered in the European Clinical Trials Database (EudraCT 2017-004226-15). All participants will give written informed consent to participate prior to any study-related procedures. The results will be presented at international conferences and published in peer-reviewed journals.

  • rheumatoid arthritis
  • ankylosing spondylitis
  • chronic pain
  • treatment with medical cannabis

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

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Footnotes

  • Contributors OH wrote the protocol for the European and the Danish Medicines Agency and the Research Ethics Committee. TEA, AAC, JP, EMH, TE, TIH, AGB, AGL, ABB, MØ, MLH, NSK, KKR, KHP and OH contributed to study concept. KHP, MØ and OH drafted and revised the manuscript after feedback from all authors. All authors contributed to the review of the present manuscript and approved the final version of the manuscript.

  • Funding The Danish Rheumatism Association, represented by OH. The Danish Rheumatism Association, The Region of Southern Denmark and the Knud and Edith Eriksen Foundation have funded this investigator-initiated study.

  • Disclaimer OH: has received fees for speaking and/or and travel expenses from AbbVie, Roche, Novartis and Pfizer. JP: has received speaker and/or consulting fees and refund for travelling expenses from Pfizer and BMS. EMH: has received fees for speaking and/or consulting from MSD, AbbVie, UCB and Sobi; research funding to Aarhus University Hospital from Roche and Novartis; and travel expenses from Pfizer, Celgene, MSD, Sobi and Roche. AGL: has received fees for speaking and/or consulting from MSD, Novartis and Pfizer; research funding from Novartis and travel expenses from AbbVie, MSD, Novartis, Pfizer and Roche. MØ: has received speaker and/or consulting fees and/or travel expenses from AbbVie, BMS, Boehringer-Ingelheim, Celgene, Eli-Lilly, Hospira, Janssen, Merck, Novartis, Novo, Orion, Pfizer, Regeneron, Roche and UCB, and research support from Abbvie, Celgene, Centocor, Merck and Novartis. MLH: has received fees for speeking and or consulting from AbbVie, Biogen, BrMS, CellTrion, Eli Lilly, MSD, Novartis, Orion, Pfizer, Roche and Samsung. KHP: has received travel expenses from Roche and Pfizer

  • Competing interests None declared.

  • Ethics approval The protocol (version 8.1., 22 November 2018) is approved by the Danish Ethics Committee (S-20170217), the Danish Data Protection Agency (2018-41-5388) and the Danish Medicines Agency (2018-0 10 018).

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

  • Patient consent for publication Not required.

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