Daphnée Brazeau

Introduction Acute pain levels following orthopaedic injury (eg, fracture) are a predictor of the onset of chronic pain, which affects nearly 50% of fracture patients and impairs functional recovery. Among current pharmacological treatments for acute pain, non-steroidal anti-inflammatory drugs have been associated with delayed bone healing, while opioids inhibit effective bone remodelling, increase the risk of pseudarthrosis and carry a high risk of addiction. In light of this, the development of new pain treatments is essential. Cannabidiol (CBD), a non-addictive and non-psychotropic cannabis component stands out as a potential therapeutic agent, given its analgesic and anti-inflammatory properties as well as its potential benefits for bone healing. This randomised controlled trial aims to investigate the effect of acute CBD treatment, compared with placebo, on patients’ self-reported pain, inflammation and well-being following a fracture injury. Methods and analysis This is a triple-blind, randomised, placebo-controlled clinical trial. A total of 225 adults aged 18–70 years, who have suffered a long bone fracture and were treated at the Hôpital du Sacré-Coeur de Montréal, will be randomly assigned within 1 week to one of three treatment arms (25 mg or 50 mg of CBD or placebo) for 1 month. The primary outcome will be the difference in the pain score between groups at 1-month follow-up. Secondary outcomes will include measures of persistent pain, inflammation, opioid usage, quality of life, sleep quality, depression, anxiety, cognition and orthopaedic function. Data will be collected at baseline, 1-month and 3-month follow-ups. Ethics and dissemination This study obtained a Health Canada licence for use of cannabis products. It has also been approved by Health Canada and the Research Ethics Board of the CIUSSS du Nord-de-l’Île-de-Montréal (Project ID 2025-2105). The findings will be published in a peer-reviewed journal and presented at local, national and international conferences. The trial’s results will be made publicly available on the ClinicalTrials.gov database. Trial registration number NCT06448923.

Objective: In a recent sham-controlled 13-session prolonged continuous theta burst stimulation intervention protocol, recovery from upper limb fracture at both 1 and 3 months was better than anticipated in patients assigned to the sham intervention group. To determine whether potential placebo effect and close patient monitoring affected recovery, the current study aimed to compare clinical outcomes between sham-treated participants who also received standard care with similarly injured patients who only received standard care. Methods: Twenty participants with isolated upper limb fractures from the sham group were seen 13 times post-fracture (1 baseline session, 10 treatments, and 2 follow-ups [1 and 3 months]) over 3 months. They completed the self-reported Disabilities of Arm, Shoulder, and Hand (DASH) questionnaire and the Numerical Rating Scale for pain assessment at 1 and 3 months post-fracture. Two control groups were recruited: 43 participants at 1 month post-fracture and another 40 participants at 3 months post-fracture. These control groups completed the same questionnaires online, without any lab visits. Results: At 1 month, patients from the sham group reported significantly less functional impairments on the DASH (p = .010). At 3 months, significantly more patients from the control group reported functional limitations (72.5% versus sham’s 40%, p = .015). Conclusions: Although preliminary, these findings suggest clinically significant beneficial effects of the sham intervention over the standard care groups. This positive sham intervention effect may be attributed to a placebo response that includes the placebo effect associated with sham rTMS, but also the impact of various factors such as the close monitoring of the injury.

Introduction Therapeutic interventions for disorders of consciousness lack consistency; evidence supports non-invasive brain stimulation, but few studies assess neuromodulation in acute-to-subacute brain-injured patients. This study aims to validate the feasibility and assess the effect of a multi-session transcranial alternating current stimulation (tACS) intervention in subacute brain-injured patients on recovery of consciousness, related brain oscillations and brain network dynamics. Methods and analyses The study is comprised of two phases: a validation phase (n=12) and a randomised controlled trial (n=138). Both phases will be conducted in medically stable brain-injured adult patients (traumatic brain injury and hypoxic-ischaemic encephalopathy), with a Glasgow Coma Scale score ≤12 after continuous sedation withdrawal. Recruitment will occur at the intensive care unit of a Level 1 Trauma Centre in Montreal, Quebec, Canada. The intervention includes a 20 min 10 Hz tACS at 1 mA intensity or a sham session over parieto-occipital cortical sites, repeated over five consecutive days. The current’s frequency targets alpha brain oscillations (8–13 Hz), known to be associated with consciousness. Resting-state electroencephalogram (EEG) will be recorded four times daily for five consecutive days: pre and post-intervention, at 60 and 120 min post-tACS. Two additional recordings will be included: 24 hours and 1-week post-protocol. Multimodal measures (blood samples, pupillometry, behavioural consciousness assessments (Coma Recovery Scale-revised), actigraphy measures) will be acquired from baseline up to 1 week after the stimulation. EEG signal analysis will focus on the alpha bandwidth (8–13 Hz) using spectral and functional network analyses. Phone assessments at 3, 6 and 12 months post-tACS, will measure long-term functional recovery, quality of life and caregivers’ burden. Ethics and dissemination Ethical approval for this study has been granted by the Research Ethics Board of the CIUSSS du Nord-de-l’Île-de-Montréal (Project ID 2021–2279). The findings of this two-phase study will be submitted for publication in a peer-reviewed academic journal and submitted for presentation at conferences. The trial’s results will be published on a public trial registry database (ClinicalTrials.gov). Trial registration number NCT05833568.