Abstract
BackgroundKnee osteoarthritis is a major cause of pain and disability. Pain control is poor, with most patients remaining in moderate to severe pain. This may be because central causes of pain, a common contributor to knee pain, are not affected by current treatment strategies. Antidepressants, such as amitriptyline, have been used to treat chronic pain in other conditions. The aim of this randomised, double blind, controlled trial, is to determine whether low dose amitriptyline reduces pain in people with painful knee osteoarthritis over 3 months compared to benztropine, an active placebo.Methods/designOne hundred and sixty people with painful radiographic knee osteoarthritis will be recruited via clinicians, local and social media advertising. Participants will be randomly allocated in a 1:1 ratio to receive either low dose amitriptyline (25 mg) or active placebo (benztropine mesylate, 1 mg) for 3 months. The primary outcome is change from baseline in knee pain (WOMAC pain subscale) at 12 weeks. Secondary outcomes include change in function (total WOMAC) and the proportion of individuals achieving a substantial response (≥ 50% reduction in pain intensity, measured by Visual Analog Scale, VAS, from no pain to worst pain imaginable, 0-100 mm) and moderate response (≥ 30% reduction in pain intensity, measured by VAS) at 12 weeks. Intention to treat analyses will be performed. Subgroup analyses will be done.DiscussionThis study will provide high level evidence regarding the effectiveness of low dose amitriptyline compared to benztropine in reducing pain and improving function in knee OA. This trial has the potential to provide an effective new therapeutic approach for pain management in knee osteoarthritis, with the potential of ready translation into clinical practice, as it is repurposing an old drug, which is familiar to clinicians and with a well described safety record.Trial registrationAustralian New Zealand Clinical Trials Registry prior to recruitment commencing (ACTRN12615000301561, March 31, 2015, amended 14 December 2018, February 2021). Additional amendment requested 18 July 2021.
Highlights
Knee osteoarthritis is a major cause of pain and disability
This study will provide high level evidence regarding the effectiveness of low dose amitriptyline compared to benztropine in reducing pain and improving function in knee OA
This trial has the potential to provide an effective new therapeutic approach for pain management in knee osteoarthritis, with the potential of ready translation into clinical practice, as it is repurposing an old drug, which is familiar to clinicians and with a well described safety record
Summary
We propose a single centre, randomised, double blind controlled clinical trial to determine whether the use of amitriptyline reduces knee pain, function and provides overall benefit in people with knee OA. The recent related Cochrane reviews have suggested that in unselected patients, overall, these do not show efficacy, the proportion of patients showing improvement is higher in the treated group [46, 47] Most of these studies did not use an active placebo, and were more likely to have been subject to unblinding, as the anticholinergic effects occur at low dose. We will examine whether the proportion benefiting is higher in those on active treatment, and attempt to identify which are more likely to benefit based on subgroups identified using simple clinical tools (eg severity of pain, radiographic change, painDETECT for pain sensitisation, Pittsburgh sleep quality index for sleep quality, HADS for mood disorders, etc) This current trial has a number of strengths.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
