Exploring the salivary proteome following intraglandular mesenchymal stromal cell therapy for radiation-induced hyposalivation in previous head and neck cancer patients: a secondary study protocol for the MESRIX-III, randomised, controlled trial

Background: Intraglandular therapy with adipose-derived mesenchymal stromal cells (ASCs) for radiation-induced xerostomia and hyposalivation has shown promising effects on the salivary flow rate and in patient-reported outcomes. However, the mode of action is not fully understood, but changes in the salivary proteome have been observed. 

Methods: This sub study, to the randomised, double-blinded, placebo-controlled trial investigating intraglandular mesenchymal stromal cells for radiation-induced hyposalivation (MESRIX-III), examines changes in the salivary proteome following intraglandular therapy into the submandibular glands with allogenic ASCs in unstimulated whole saliva (UWS) in previous head and neck cancer patients with radiation-induced hyposalivation. A total of 120 patients were included and randomised in a 1:1 ratio to receive intraglandular injections with either ASCs or placebo (CryoStor10, 10% dimethyl sulfoxide, Biolife Solutions). UWS samples was collected at baseline and at 4 months post transplantation. The main endpoint is comparison of the salivary human proteome evaluated by mass spectrometry analysis in the group receiving ASCs compared to placebo at 4 months. Secondary outcomes are comparison of the microbial proteome in the group receiving ASCs compared to placebo at 4 months; changes in the salivary proteome and microbial proteome in the group receiving ASCs from baseline to 4 months and evaluation of the salivary proteome and microbial proteome following radiation therapy at baseline in both groups. 

Discussion: This study will gain insights into the potential mode of action of intraglandular ASC therapy for radiation-induced hyposalivation. The results may open avenues for a clinically applicable and disease-modifying treatment to ameliorate hyposalivation and restore salivary gland function following radiation therapy in previous head and neck cancer patients. Moreover, it will constitute the most extensive collection of data characterising the salivary proteome post-radiation therapy in the head and neck region. 

Trial registration: The MESRIX-III study is approved by the Danish Data Protection Agency (protocol number P-2020–1164), the National Ethics Committee (protocol number: 1802872) and the Danish Medical Agency (2018–000348-24) and is registered at the ClinicalTrials.gov database (NCT04776538). First posted on clinicaltrials.gov 03-JAN-2021.