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

Oliver Hendricks; Tonny Elmose Andersen; Afshin Ashouri Christiansen; Jette Primdahl; Ellen Margrethe Hauge; Torkell Ellingsen; Tina Ingrid Horsted; Anja Godske Bachmann; Anne Gitte Loft; Anders Bo Bojesen; Mikkel Østergaard; Merete Lund Hetland; Niels Steen Krogh; Kirsten Kaya Roessler; Kim Hørslev-Petersen

doi:10.1136/bmjopen-2018-028197

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

Oliver Hendricks^*, Tonny Elmose Andersen, Afshin Ashouri Christiansen, Jette Primdahl, Ellen Margrethe Hauge, Torkell Ellingsen, Tina Ingrid Horsted, Anja Godske Bachmann, Anne Gitte Loft, Anders Bo Bojesen, Mikkel Østergaard, Merete Lund Hetland, Niels Steen Krogh, Kirsten Kaya Roessler, Kim Hørslev-Petersen

^*Corresponding author for this work

Department of Clinical Medicine

2 Citations (Scopus)

22 Downloads (Pure)

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.

Original language	English
Article number	e028197
Journal	BMJ Open
Volume	9
Issue number	6
Number of pages	9
ISSN	2044-6055
DOIs	https://doi.org/10.1136/bmjopen-2018-028197
Publication status	Published - 2019

Keywords

ankylosing spondylitis
chronic pain
rheumatoid arthritis
treatment with medical cannabis

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Hendricks, O., Andersen, T. E., Christiansen, A. A., Primdahl, J., Hauge, E. M., Ellingsen, T., Horsted, T. I., Bachmann, A. G., Loft, A. G., Bojesen, A. B., Østergaard, M., Lund Hetland, M., Krogh, N. S., Roessler, K. K., & Hørslev-Petersen, K. (2019). 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. BMJ Open, 9(6), Article e028197. https://doi.org/10.1136/bmjopen-2018-028197

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. / Hendricks, Oliver; Andersen, Tonny Elmose; Christiansen, Afshin Ashouri et al.
In: BMJ Open, Vol. 9, No. 6, e028197, 2019.

Research output: Contribution to journal › Journal article › Research › peer-review

Hendricks, O, Andersen, TE, Christiansen, AA, Primdahl, J, Hauge, EM, Ellingsen, T, Horsted, TI, Bachmann, AG, Loft, AG, Bojesen, AB, Østergaard, M , Lund Hetland, M, Krogh, NS, Roessler, KK & Hørslev-Petersen, K 2019, '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', BMJ Open, vol. 9, no. 6, e028197. https://doi.org/10.1136/bmjopen-2018-028197

Hendricks O, Andersen TE, Christiansen AA, Primdahl J, Hauge EM, Ellingsen T et al. 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. BMJ Open. 2019;9(6):e028197. doi: 10.1136/bmjopen-2018-028197

Hendricks, Oliver ; Andersen, Tonny Elmose ; Christiansen, Afshin Ashouri et al. / 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. In: BMJ Open. 2019 ; Vol. 9, No. 6.

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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.",

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T1 - 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

T2 - Protocol for a multicentre, randomised, placebo-controlled study

AU - Hendricks, Oliver

AU - Andersen, Tonny Elmose

AU - Christiansen, Afshin Ashouri

AU - Primdahl, Jette

AU - Hauge, Ellen Margrethe

AU - Ellingsen, Torkell

AU - Horsted, Tina Ingrid

AU - Bachmann, Anja Godske

AU - Loft, Anne Gitte

AU - Bojesen, Anders Bo

AU - Østergaard, Mikkel

AU - Lund Hetland, Merete

AU - Krogh, Niels Steen

AU - Roessler, Kirsten Kaya

AU - Hørslev-Petersen, Kim

PY - 2019

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N2 - 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.

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KW - chronic pain

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KW - treatment with medical cannabis

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