Effect of liraglutide on body weight and pain in patients with overweight and knee osteoarthritis: protocol for a randomised, double-blind, placebo-controlled, parallel-group, single-centre trial

Henrik Gudbergsen, Marius Henriksen, Eva Ejlersen Wæhrens, Anders Overgaard, Henning Bliddal, Robin Christensen, Mikael Ploug Boesen, Filip K Krag Knop, Arne Astrup, Marianne Uggen Rasmussen, Cecilie Bartholdy, Cecilie Daugaard, Else Marie Bartels, Karen Ellegaard, Berit Lilienthal Heitmann, Lars Erik Kristensen, Henrik Gudbergsen, Marius Henriksen, Eva Ejlersen Wæhrens, Anders Overgaard, Henning Bliddal, Robin Christensen, Mikael Ploug Boesen, Filip K Krag Knop, Arne Astrup, Marianne Uggen Rasmussen, Cecilie Bartholdy, Cecilie Daugaard, Else Marie Bartels, Karen Ellegaard, Berit Lilienthal Heitmann, Lars Erik Kristensen

Abstract

Introduction: With an increasing prevalence of citizens of older age and with overweight, the health issues related to knee osteoarthritis (OA) will intensify. Weight loss is considered a primary management strategy in patients with concomitant overweight and knee OA. However, there are no widely available and feasible methods to sustain weight loss in patients with overweight and knee OA. The present protocol describes a randomised controlled trial evaluating the efficacy and safety of the glucagon-like peptide-1 receptor agonist liraglutide in a 3 mg/day dosing in patients with overweight and knee OA.

Methods and analysis: 150 volunteer adult patients with overweight or obesity and knee OA will participate in a randomised, double-blind, placebo-controlled, parallel-group and single-centre trial. The participants will partake in a run-in diet intervention phase (week -8 to 0) including a low calorie diet and dietetic counselling. At week 0, patients will be randomised to either liraglutide 3 mg/day or liraglutide placebo 3 mg/day for 52 weeks as an add-on to dietetic guidance on re-introducing regular foods and a focus on continued motivation to engage in a healthy lifestyle. The co-primary outcomes are changes in body weight and the Knee Injury and Osteoarthritis Outcome Score pain subscale from week 0 to week 52.

Ethics and dissemination: The trial has been approved by the regional ethics committee in the Capital Region of Denmark, the Danish Medicines Agency and the Danish Data Protection Agency. An external monitoring committee (The Good Clinical Practice Unit at Copenhagen University Hospitals) will oversee the trial. The results will be presented at international scientific meetings and through publications in peer-reviewed journals.

Trial registration numbers: 2015-005163-16, NCT02905864, U1111-1171-4970 BASED ON PROTOCOL VERSION: V.6; 30 January 2017, 15:30 hours.

Keywords: dietary intervention; knee; liraglutide; osteoarthritis; overweight; weight loss.

Conflict of interest statement

Competing interests: HG has received speaker fees from Pfizer and MSD. MB has received speaker fees from Esaote, AbbVie and UCB. FKKK has received lecture fees from, participated in advisory boards of and/or consulted for Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, MSD/Merck, Novo Nordisk, Sanofi and Zealand Pharma. AA is member of advisory boards/consultant for Acino, Switzerland, BioCare Copenhagen, DK, Gelesis, USA, Groupe Éthique et Santé, France, McCain Foods Limited, USA, Novo Nordisk, DK, Pfizer, USA, Saniona, DK, Weight Watchers, USA and Zaluvida, Switzerland. He is recipient of travel grants and honoraria as speaker for a wide range of Danish and international concerns. Commercial interests: co-owner and member of the Board of the consultancy company Dentacom Aps, Denmark (2005). Co-founder and co-owner of UCPH spin-outs Mobile Fitness A/S (2005), Flaxslim ApS (were also member of Board, 2015, and Personalized Weight Management Research Consortium ApS (Gluco-diet.dk, 2017). Co-inventor of a number of patents owned by UCPH, in accordance with Danish law. AA is not advocate or activist for specific diets, and is not strongly committed to any specific diet, for example, veganism, Atkins diet, gluten-free diet, high animal protein diet or dietary supplements. LEK has received fees for speaking and consultancy from Pfizer, AbbVie, Amgen, Sanofi, UCB, Celgene, BMS, Biogen, Novo Nordisk, MSD, Novartis, Eli Lilly and Janssen Pharmaceuticals.

© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1
Figure 1
Trial design.

References

    1. Hawkes C, Jewell J, Allen K. A food policy package for healthy diets and the prevention of obesity and diet-related non-communicable diseases: the NOURISHING framework. Obes Rev 2013;14:159–68. 10.1111/obr.12098
    1. Greenway FL. Physiological adaptations to weight loss and factors favouring weight regain. Int J Obes 2015;39:1188–96. 10.1038/ijo.2015.59
    1. Felson DT, Lawrence RC, Dieppe PA, et al. . Osteoarthritis: new insights. Part 1: the disease and its risk factors. Ann Intern Med 2000;133:635–46. 10.7326/0003-4819-133-8-200010170-00016
    1. Peat G, McCarney R, Croft P. Knee pain and osteoarthritis in older adults: a review of community burden and current use of primary health care. Ann Rheum Dis 2001;60:91–7. 10.1136/ard.60.2.91
    1. Coggon D, Reading I, Croft P, et al. . Knee osteoarthritis and obesity. Int J Obes Relat Metab Disord 2001;25:622–7. 10.1038/sj.ijo.0801585
    1. Bliddal H, Leeds AR, Christensen R. Osteoarthritis, obesity and weight loss: evidence, hypotheses and horizons - a scoping review. Obes Rev 2014;15:578–86. 10.1111/obr.12173
    1. le Roux CW, Astrup A, Fujioka K, et al. . 3 years of liraglutide versus placebo for type 2 diabetes risk reduction and weight management in individuals with prediabetes: a randomised, double-blind trial. Lancet 2017;389:1399–409. 10.1016/S0140-6736(17)30069-7
    1. Hochberg MC, Altman RD, April KT, et al. . American College of Rheumatology 2012 recommendations for the use of nonpharmacologic and pharmacologic therapies in osteoarthritis of the hand, hip, and knee. Arthritis Care Res 2012;64:465–74. 10.1002/acr.21596
    1. Fernandes L, Hagen KB, Bijlsma JW, et al. . EULAR recommendations for the non-pharmacological core management of hip and knee osteoarthritis. Ann Rheum Dis 2013;72:1125–35. 10.1136/annrheumdis-2012-202745
    1. McAlindon TE, Bannuru RR, Sullivan MC, et al. . OARSI guidelines for the non-surgical management of knee osteoarthritis. Osteoarthritis Cartilage 2014;22:363–88. 10.1016/j.joca.2014.01.003
    1. Zhang W, Nuki G, Moskowitz RW, et al. . OARSI recommendations for the management of hip and knee osteoarthritis: part III: Changes in evidence following systematic cumulative update of research published through January 2009. Osteoarthritis Cartilage 2010;18:476–99. 10.1016/j.joca.2010.01.013
    1. Roos EM, Lohmander LS. The Knee injury and Osteoarthritis Outcome Score (KOOS): from joint injury to osteoarthritis. Health Qual Life Outcomes 2003;1:64 10.1186/1477-7525-1-64
    1. Bellamy N, Buchanan WW, Goldsmith CH, et al. . Validation study of WOMAC: a health status instrument for measuring clinically important patient relevant outcomes to antirheumatic drug therapy in patients with osteoarthritis of the hip or knee. J Rheumatol 1988;15:1833–40.
    1. Hawker GA, Davis AM, French MR, et al. . Development and preliminary psychometric testing of a new OA pain measure--an OARSI/OMERACT initiative. Osteoarthritis Cartilage 2008;16:409–14. 10.1016/j.joca.2007.12.015
    1. Kessler S, Grammozis A, Günther KP, et al. . [The intermittent and constant pain score (ICOAP) - a questionnaire to assess pain in patients with gonarthritis]. Z Orthop Unfall 2011;149:22–6. 10.1055/s-0030-1249967
    1. Posner K, Brown GK, Stanley B, et al. . The Columbia-Suicide Severity Rating Scale: initial validity and internal consistency findings from three multisite studies with adolescents and adults. Am J Psychiatry 2011;168:1266–77. 10.1176/appi.ajp.2011.10111704
    1. Kroenke K, Spitzer RL, Williams JB. The PHQ-9: validity of a brief depression severity measure. J Gen Intern Med 2001;16:606-13.
    1. Gormally J, Black S, Daston S, et al. . The assessment of binge eating severity among obese persons. Addict Behav 1982;7:47–55. 10.1016/0306-4603(82)90024-7
    1. Kolotkin RL, Crosby RD, Kosloski KD, et al. . Development of a brief measure to assess quality of life in obesity. Obes Res 2001;9:102–11. 10.1038/oby.2001.13
    1. Brod M, Hammer M, Kragh N, et al. . Development and validation of the Treatment Related Impact Measure of Weight (TRIM-Weight). Health Qual Life Outcomes 2010;8:19 10.1186/1477-7525-8-19
    1. Ware JE, Sherbourne CD. The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection. Med Care 1992;30:473–83.
    1. Christensen R, Henriksen M, Leeds AR, et al. . Effect of weight maintenance on symptoms of knee osteoarthritis in obese patients: a twelve-month randomized controlled trial. Arthritis Care Res 2015;67:640–50. 10.1002/acr.22504

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