Sjögren´s Syndrome, Xerostomia Due to Hyposecretion of Salivary Gland, Xerostomia Due to Radiotherapy
Conditions
Keywords
Mesenchymal Stem Cell, Sjögren, Radiation, xerostomia, Head and Neck cancer
Brief summary
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.
Interventions
Suspended in 10% DMSO. Manufactured by OUH CELL BENCH in Odense, Denmark.
DRUGPlacebo
Sterile isotonic saline water
Sponsors
Christian von Buchwald
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
One research assistant preparing the treatments are unmasked
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Unstimulated whole salivary flow rate | T=0 months, T=4 months and T=8 months (primary endpoint assessed after 8 months) | Unstimulated whole salivary flow rate measured in mL/min |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Patient-Reported Outcome of xerostomia: The Groningen Radiotherapy-Induced Xerostomia questionnaire (GRIX). | T=0 months, T=4 months, T=8 months (Key secondary endpoint assessed after 8 months). | For evaluation of the participants´ perception of xerostomia, the participants will answer validated questionnaires in Danish. |
| 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). | T=0 months, T=4 months, T=8 months (Key secondary endpoint assessed after 8 months). | 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 |
| Immune response | T=0 months, T=4 months, T=8 months (Key secondary endpoint assessed after 8 months). | Measured by positivity of de novo drug specific antibodies (binary outcome) |
| Patient Reported Outcome: Goal Attainment Scale (GAS) | T=0 months, T=4 months, T=8 months (Key secondary endpoint assessed after 8 months). | 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. |
| Stimulated whole salivary flow rate | T=0 months, T=4 months, T=8 months (Key secondary endpoint assessed after 8 months). | Stimulated whole salivary flow rate measured in mL/min |
Other
| Measure | Time frame | Description |
|---|---|---|
| 5-point transition scale for determining the minimal important difference (evaluated at 8 months) | T=4 months, T=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. |
| 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 | — |
| Incidence of treatment-related adverse events and serious adverse events | Continually assessed from inclusion (T=0 months) to last visit (T=24 months). | Evaluated by serious adverse events (SAEs), Suspected Unexpected Serious Adverse Reactions (SUSARs), treatment-related adverse events, and deaths. |
Contacts
Primary ContactJoachim Hansen, M.D
Outcome results
None listed