Total mesorectal excision (TME) is highly effective for early-stage rectal cancer, but is associated with considerable morbidity, which can substantially impair the quality of life (QoL) of patients. For very early tumours (low-risk cT1), local excision (LE) offers the possibility of organ preservation (OP) with reduced morbidity; however, its application is limited to a selected group. For early tumours where upfront LE is not feasible, primary OP with (chemo)radiotherapy as an alternative to TME surgery has been evaluated in the STARTREC phase II/III studies, which reported promising 1-year OP rates.

The STARTREC-3 trial aims to increase the 2-year OP rate from 60% to 80% in early rectal cancer (cT1–3abN0) and from 30% to 60% in early-intermediate rectal cancer (cT1–3abN1, ≤3 mesorectal nodes measuring ≤8 mm) by intensifying neoadjuvant treatment in different study arms.

STARTREC-3 is embedded in the STARTREC master trial protocol, which uses an adaptive platform study design allowing early termination of inferior treatment arms and the addition of novel arms. The multicentre STARTREC-3 trial investigates three parallel, non-comparative treatment strategies for patients with early and early-intermediate rectal adenocarcinoma who prefer OP over primary TME surgery. All arms start with 5x5 Gy radiotherapy, followed by: an endoluminal boost via contact X-ray brachytherapy (arm 1), an external beam radiotherapy (EBRT) boost by MR-guided EBRT (arm 2) or three cycles of capecitabine oxaliplatin systemic treatment chemotherapy (arm 3). Treatment allocation is predefined and centre-dependent. Response evaluations (MRI and endoscopy) are planned at 14–16 weeks and 26 weeks after onset of radiotherapy. The primary endpoint is the proportion of patients with successful OP at 24 months from onset of therapy. Secondary endpoints include toxicity, QoL, functional and oncological outcomes. Data will be analysed separately for early (cN0) and early-intermediate (cN1) disease. The total planned sample size is 210 patients across the three arms. Interim analyses will be performed for each study arm to determine early failures and discontinue ineffective arms.

The trial was approved by the medical ethics committee NedMec of the Netherlands and is registered in the EU Clinical Trials Information System (CTIS). The results will be published in an international peer-reviewed journal.

CTIS EU 2024-514620-17-00

Osteoarthritis (OA) is a degenerative and progressive joint condition causing pain and disability. Physical exercise is recognised as the most effective intervention since individuals with this condition often experience muscle weakness, balance deficits and chronic pain. Additionally, knee osteoarthritis (KOA) is associated with central sensitisation, contributing to chronic pain conditions. Transcranial Direct Current Stimulation (tDCS), a non-invasive neuromodulation technique, has been employed to induce changes in pain perception by altering cortical excitability, potentially reducing chronic pain.

This is a protocol for a randomised controlled trial. Participants will be allocated to two groups: G1 (active tDCS combined with exercise) and G2 (sham tDCS combined with exercise). The intervention protocol will last for 5 weeks, with two sessions per week on non-consecutive days. Pain intensity will be assessed as the primary outcome using the Numeric Rating Scale (NRS). The sample size was calculated based on a minimum clinically important difference of 3 points on the NRS between groups, with a statistical power of 80% and a significance level of 5%. Secondary outcomes will include physical function and global perceived change.

This protocol was approved by the Research Ethics Committee of the Trairi School of Health Sciences, Federal University of Rio Grande do Norte (Approval Number: 6.801.827), and it is in accordance with the Declaration of Helsinki for human research. Results will be published in peer-reviewed journals and presented at scientific events. This trial is registered in the Brazilian Clinical Trials Registry.

Brazilian Clinical Trials Registry (RBR-5pb2g33).