Long-term sickness absence represents a major public health challenge with far-reaching consequences for both individuals and society. Musculoskeletal disorders (MSDs) are among the leading causes of sickness absence. Although mobile apps show promise for supporting self-management of MSDs, high-quality evidence remains limited, and outcomes related to work participation are rarely examined. This trial aims to evaluate whether an individually tailored, app-based self-management intervention (SmaRTWork), provided in addition to usual care, improves return-to-work compared with usual care alone among individuals on sick leave due to MSDs.

We will conduct a randomised controlled trial with two parallel arms: 1) SmaRTWork in addition to usual care and 2) usual care alone. Individuals 20–59 years old who have been sick-listed for

The trial is approved by the Committees for Clinical Trials of Pharmaceuticals and Medical Devices (Ref. 563919). Results will be published in peer-reviewed journals and presented at national and international conferences.

NCT07034040.

Emerging evidence supports a role for interleukin 6 (IL-6), a pro-inflammatory cytokine, in the pathogenesis of treatment-resistant major depressive disorder (TRD). However, interventional studies targeting IL-6 in this population remain scarce. Tocilizumab is a humanised monoclonal antibody that inhibits IL-6 signalling and is approved for the treatment of autoimmune conditions such as rheumatoid arthritis. The primary objective of this study is to examine whether IL-6 inhibition via tocilizumab can impact depressive symptoms, inflammation-related biomarkers and cognition in patients with TRD. A secondary objective is to compare the biological profiles of patients with TRD with elevated inflammation to those of healthy controls.

This is a proof-of-concept, randomised, parallel-group, triple-blind, placebo-controlled clinical trial. 22 adult outpatients diagnosed with TRD and evidence of low-grade inflammation (serum C reactive protein≥3 mg/L) will be randomised (1:1) to receive either one intravenous infusion of tocilizumab (8 mg/kg; maximum 800 mg) or normal saline, administered as an add-on to their ongoing treatment. Psychiatric, cognitive and biomarker assessments will be performed at baseline and at follow-up visits on days 7, 14 and 28 post-infusion. Additionally, 10 healthy controls with no psychiatric history will undergo the same baseline assessments for biomarker comparison.

The study has been approved by the Research Ethics Committee of the Hospital de Clínicas de Porto Alegre (Project number: 2025-0245, CAAE: 88904825.7.0000.5327). Findings will be disseminated through peer-reviewed publications, scientific meetings and, on request, lay summaries for participants.

NCT07052058.