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.

Pancreatic adenocarcinoma is a major public health concern due to its high metastatic potential and poor prognosis. However, treatment options remain limited. A promising therapeutic strategy involves the sequential administration of standard therapies. In a previous phase Ib-II trial, we evaluated a sequential regimen of gemcitabine plus nab-paclitaxel (GEMBRAX) followed by FOLFIRINOX (FFX), which improved median overall survival (OS), progression-free survival and objective response rate (ORR), with acceptable toxicity. This phase II randomised trial will assess the efficacy of GEMBRAX followed by FFX compared with FFX alone as a first-line treatment for metastatic pancreatic cancer (mPC).

The GABRINOX-2 (GemcitabineABRaxaneIRInotecanOXaliplatine-2) study is an ongoing prospective, multicentre, randomised phase II trial. A total of 162 patients with mPC will be randomised (1:1) to receive GEMBRAX treatment followed by FFX (arm A) or FFX alone (arm B). The primary objective is to compare the efficacy of GEMBRAX followed by FFX with FFX alone as a first-line treatment for mPC. Secondary objectives include treatment tolerability, ORR, disease control rate, OS and patient quality of life. Additionally, we aim to identify novel biomarkers associated with treatment response through the analysis of circulating tumour DNA and assess the messenger RNA signature’s predictive value for OS based on treatment approach.

This study was approved by the comité de protection des personnes Ile de France III (26 July 2021) and the French National Agency for the Safety of Health Products (17 September 2021). It will be carried out in accordance with European Reglementation 536/2014 on clinical trials, the Declaration of Helsinki, Good Clinical Practice guidelines and the French Public Health Code. The results will be published in peer-reviewed journals and presented at national and international conferences.

This trial has been registered on euclinicaltrials.eu (EU 2023-508594-84-00) and on clinicaltrials.gov (NCT05065801).