Effectiveness and safety of mesenchymal stem/stromal cell for radiation-induced hyposalivation and xerostomia in previous head and neck cancer patients (MESRIX-III): a study protocol for a single-centre, double-blinded, randomised, placebo-controlled, phase II study

Abstract Background A predominant side effect of radiotherapy for head and neck cancer is salivary gland hypofunction and xerostomia leading to debilitating oral disorders and impaired quality of life (QoL). Intraglandular mesenchymal stem cell therapy has shown promising results as a treatment for xerostomia. Methods This is a randomised, double-blinded, placebo-controlled, parallel-group, prospective, single-centre trial investigating the safety, tolerability, and effectiveness of allogeneic stem cells as a treatment for radiation-induced hyposalivation and xerostomia for previous head and neck cancer patients. We will include a total of 120 patients who previously have been treated with radiotherapy for a head and neck cancer in Denmark. Participants will be randomly assigned using block randomisation to one of two parallel groups in a 1:1 ratio to receive ultrasound-guided injection of allogeneic adipose-derived mesenchymal stem cell (ASC) (n = 60) or placebo (n = 60) into the submandibular glands. Placebo will consist of CryoStor10 (BiolifeSolutions), the freeze media for ASCs containing 10% dimethyl sulfoxide (DMSO). The primary endpoint is change in unstimulated whole saliva flow rate. The secondary endpoints are change in stimulated whole saliva flow rate, QoL, and composition of saliva. Further secondary endpoints are safety and immune response (human leukocyte antigen (HLA) response) to the stem cells will be assessed. Patients are evaluated at baseline (before treatment), after 4 months, and after 12 months. All study personnel, except study personnel thawing and preparing the treatment for injection, and participants will be blinded to group assignment. Unblinded study personnel will not participate in the outcome assessment. Discussion The trials will investigate the efficacy and safety of ASC injection to the submandibular gland as a potential new treatment for post-radiation xerostomia. We hope the results will pave the way for a clinically relevant treatment to ameliorate patients with xerostomia, a severely hampering condition. Trial registration The study is approved by the Danish Data Protection Agency (protocol number P-2020-1164), the National Ethics Committee protocol number: (Protocol number: 1802872), and the Danish Medical Agency (2018-000348-24). The protocol was registered at the ClinicalTrials.gov database (NCT04776538).