Study protocol for a randomised, double-blind, placebo-controlled clinical trial of duloxetine for the treatment and prevention of musculoskeletal pain: altering the transition from acute to chronic pain (ATTAC pain)

Abstract

IntroductionChronic musculoskeletal pain affects a substantial portion of adults visiting the emergency department (ED). Current treatment is limited in scope and does not effectively reduce musculoskeletal pain in patients. The study will evaluate the use of duloxetine, a serotonin-norepinephrine reuptake inhibitor Food and Drug Administration approved for the treatment of chronic pain, as a promising option in its prevention. The proposed study may present a well-tolerated and effective non-opioid treatment for patients with acute musculoskeletal pain that may also be effective in preventing the transition to persistent or chronic musculoskeletal pain.Methods and analysisThe primary outcome of this study will be to assess the tolerability and preliminary effectiveness of duloxetine in patients with acute musculoskeletal pain. The study will take place at two EDs in Rhode Island, USA. The study will involve randomisation to one of three arms: duloxetine 30 mg, duloxetine 60 mg or placebo. Tolerability will be assessed by comparing the proportion of participants that report an adverse event and that drop-out across the three study arms. Effectiveness will be determined by self-reported pain over 6 weeks of follow-up. Specifically, we will compare the proportion of participants with persistent pain (ongoing pain at 6-week follow-up), across the three study arms. 60 adults (aged 18–59) presenting to the ED with acute axial musculoskeletal pain within 7 days of onset are expected to be enrolled in the proposed study.Ethics and disseminationEthics approval was obtained by the Institutional Review Board (IRB). These results will be published in a peer reviewed scientific journal and presented at one or more scientific conferences.Trial registration numberNCT03315533.

Effectiveness of Duloxetine on Oxaliplatin-induced Allodynia and Hyperalgesia in Rats

“…We found no studies of duloxetine prevention of fibromyalgia or diabetic peripheral neuropathy. A study is currently underway to evaluate the effectiveness of duloxetine for the prevention of the transition of acute to chronic musculoskeletal pain (Strauss et al, 2019), and a recent randomized clinical trial of duloxetine for the prevention of persistant musculoskeletal pain after injury or trauma shows promising results (Beaudoin et al, 2023). The lack of investigation into the use of duloxetine in prevention of fibromyalgia, diabetic neuropathy, and chronic musculoskeletal pain is a gap in the current science that should be addressed.…”

Tolerability and efficacy of duloxetine for the prevention of persistent musculoskeletal pain after trauma and injury: a pilot three-group randomized controlled trial

“…The analysis plan and protocol were published in advance of the trial's conduct. 61 The data and program codes used in this analysis are available upon request to the corresponding author, subject to approval by the investigative team and implementation of a data use agreement.…”

“…The study was registered at ClinicalTrials.gov (Identifier NCT03315533) and the trial protocol has been published elsewhere. 61 The institutional review board of the health system where the study was conducted approved the study protocol, and all participants provided written informed consent.…”