Repeated Mesenchymal Stem Cell Therapy for Radiation-Induced Hyposalivation and Xerostomia in Head and Neck Cancer Survivors (MESRIX-more)

Dry mouth leads to debilitating symptoms 24/7. The two primary causes for dry mouth are Sjögrens disease and after radiotherapy of a head and neck cancer. Former clinical trials have investigated mesenchymal stem cell treatment for dry mouth with promising results. However, few of the participants evolved normal salivary flow rate. Therefore, in this randomized clinical trial, two treatments of mesenchymal stem cells are administered, 4 months apart. This has not been done before.

The hypothesis is that two treatments of mesenchymal stem cells results in a higher salivary flow rate and ameliorate symptoms from dry mouth.

Study Overview

• Status: Not yet recruiting
• Conditions: Xerostomia Due to Radiotherapy; Sjögren´s Syndrome; Xerostomia Due to Hyposecretion of Salivary Gland
• Intervention / Treatment: Drug: ALLOGENEIC AND EXPANDED ADIPOSE TISSUE-DERIVED MESENCHYMAL STEM CELLS; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Joachim Hansen, M.D; Phone Number: +4523312552; Email: joachim.hansen.01@regionh.dk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Former radiotherapy for squamous cell carcinoma, or adenocarcinoma, of the nasal sinus, larynx, pharynx, and oral cavity
2. WHO Performance status 0-1
3. Presence of xerostomia daily
4. UWS of 0.05 mL/min to 0.5 ml/min
5. Age above 18
6. Informed consent
7. 0.5 year follow-up of the cancers in 1. with no recurrence

Exclusion Criteria:

1. Any malignant cancer diagnosis excluding head and neck cancers
2. Xerogenic medications at inclusion
3. Penicillin or streptomycin allergy assessed by health personnel
4. Any other previous or active disease of the salivary glands (e.g. Sjögren's Disease, sialolothiasis)
5. Previous submandibular surgery or biopsy
6. Pregnancy or planned pregnancy until 4 months after second treatment
7. Breastfeeding
8. Smoking within the last 6 months
9. Alcohol abuse within the last 6 months (consumption must not be above 10 units/week (Danish National board health alcohol guidelines)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Mesenchymal Stem Cells; Treatment with intraglandular injections in both submandibular glands with allogeneic adipose derived mesenchymal stem cells	Drug: ALLOGENEIC AND EXPANDED ADIPOSE TISSUE-DERIVED MESENCHYMAL STEM CELLS; Suspended in 10% DMSO. Manufactured by OUH CELL BENCH in Odense, Denmark.
Placebo Comparator: Placebo; Treatment with intraglandular injections in both submandibular glands sterile isotonic saline water	Drug: Placebo; Sterile isotonic saline water

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Unstimulated whole salivary flow rate	Unstimulated whole salivary flow rate measured in mL/min	T=0 months, T=4 months and T=8 months (primary endpoint assessed after 8 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Stimulated whole salivary flow rate	Stimulated whole salivary flow rate measured in mL/min	T=0 months, T=4 months, T=8 months (Key secondary endpoint assessed after 8 months).
Patient-Reported Outcome of xerostomia: The Groningen Radiotherapy-Induced Xerostomia questionnaire (GRIX).	For evaluation of the participants´ perception of xerostomia, the participants will answer validated questionnaires in Danish.	T=0 months, T=4 months, T=8 months (Key secondary endpoint assessed after 8 months).
Patient-Reported Outcome of xerostomia: The European organization for research and treatment of cancer quality of life questionnaire, head and neck-35 (EORTC QLQ-H&N35).	For evaluation of the participants´ perception of xerostomia, the participants will answer validated questionnaires in Danish. Patients will fill out the EORTC-QLQ- H&N35 (evaluates overall implications of the xerostomia) for the following domains: HNDR: dry mouth; HNSS: sticky saliva; HNSW: swallowing	T=0 months, T=4 months, T=8 months (Key secondary endpoint assessed after 8 months).
Immune response	Measured by positivity of de novo drug specific antibodies (binary outcome)	T=0 months, T=4 months, T=8 months (Key secondary endpoint assessed after 8 months).
Patient Reported Outcome: Goal Attainment Scale (GAS)	Goal attainment Scale (GAS) was developed in 1968 for assessing outcomes in mental health and has since been updated[36]. Now it is used in a wide variety of settings. It is a qualitative patient reported outcome measure. GAS can be beneficial in drug trials where patients have heterogenic symptoms of the disease[37]. The patient, supported by the health professional, picks 3 personal goals to be measured throughout the study period. The goals must be related to the disease and treatment. In this study 3 goals could be: 1. Ability to sleep better at night, ability to eat more solid foods, and less mouth pain. The goals are evaluated at baseline and at each follow up, following the scoring system seen in figure 1. Statistics are calculated from T-scores.	T=0 months, T=4 months, T=8 months (Key secondary endpoint assessed after 8 months).

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of treatment-related adverse events and serious adverse events	Evaluated by serious adverse events (SAEs), Suspected Unexpected Serious Adverse Reactions (SUSARs), treatment-related adverse events, and deaths.	Continually assessed from inclusion (T=0 months) to last visit (T=24 months).
Outcome 1 to 6 assessed at long term follow-up		T=0 months, T=4 months, T=8 months, T=12 months, and T=24 months
5-point transition scale for determining the minimal important difference (evaluated at 8 months)	The 5-point transition scale is critical in the exploratory secondary objective of developing Minimal Important Differences (MIDs) for all the outcome measures applied in the trial because it provides a subjective, patient-centered anchor to assess meaningful change. The scale, which typically ranges from "much worse" to "much better," captures participants' perceptions of change in their condition over time. By linking participants' responses on this scale to corresponding changes in clinical outcome measures, the transition scale helps identify the smallest change in those measures that is considered important or beneficial by the participants themselves. This subjective assessment of change is essential for establishing MIDs, as it ensures that the derived thresholds reflect clinically relevant improvements or deteriorations from the patients' perspectives.	T=4 months, T=8 months.

Collaborators and Investigators

• Sponsor: Christian von Buchwald
• Investigators: Study Chair: Christian von Buchwald, MD, Professor, Copenhagen University Hospital - Rigshospital

Study record dates

Study Major Dates

• Study Start (Estimated): December 1, 2025
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: November 18, 2025
• First Submitted That Met QC Criteria: December 4, 2025
• First Posted (Actual): December 18, 2025

Study Record Updates

• Last Update Posted (Actual): December 18, 2025
• Last Update Submitted That Met QC Criteria: December 4, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Mesenchymal Stem Cell; Radiation; Head and Neck cancer; xerostomia; Sjögren
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Mouth Diseases; Stomatognathic Diseases; Neoplasms by Site; Neoplasms; Arthritis; Joint Diseases; Rheumatic Diseases; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Eye Diseases; Arthritis, Rheumatoid; Salivary Gland Diseases; Dry Eye Syndromes; Lacrimal Apparatus Diseases; Skin and Connective Tissue Diseases; Sjogren's Syndrome; Head and Neck Neoplasms; Xerostomia
• Other Study ID Numbers: 2025-522559-25-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Due to national legislations, few data is anonymized. Therefore, we do not plan to share IPD, unfortunately. However, if it will be possible, this page will be updated.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No