Dry Mouth, Hyposalivation, Mesenchymal Stem Cells, Mesenchymal Stromal Cells, Oropharynx Cancer, Salivary Gland Diseases, Stem Cells, Xerostomia, Xerostomia Due to Radiotherapy
Conditions
Keywords
Xerostomia Due to Radiotherapy
Brief summary
An investigator-initiated, non-randomized, open label study to investigate the safety, feasibility and tolerability of intraglandular injection of allogeneic mesenchymal stem/stromal cells (MSCs) into the submandibular and parotid glands of the patients with radiation-induced hyposalivation and xerostomia after radiation for a oropharyngeal squamous cell carcinoma
Detailed description
Patients with previous oropharyngeal cancer and radiation-induced hyposalivation and xerostomia (dry mouth syndrome) will receive intraglandular injections of allogeneic adipose-derived MSCs into the submandibular and parotid glands. The trial will be Good Clinical Practice (GCP) Monitored. From healthy donors, MSCs will be produced at a Good Manufacturing Practice (GMP) Facility. The patients will be followed for four months for safety, tolerability, and efficacy registration. Changes in quality of life, unstimulated, and stimulated whole saliva flow rate, salivary gland function will be assessed. Immune response towards receiving allogeneic MSCs will be evaluated in plasma and saliva. Changes in the composition and quality of the whole saliva will be investigated. Saliva from the participants will altså be compared to saliva from ten healthy controls.
Interventions
BIOLOGICALAllogeneic adipose derived stem/stromal cells
Culture expanded allogeneic adipose derived stem/stromal cells
Sponsors
Rigshospitalet, Denmark
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
1. Age between 18-75 years 2. Previous radiotherapy +/- chemotherapy for OPSCC stage I- II (UICC-8, 2017) 3. 2 years' follow-up without recurrence 4. Clinically reduced salivation and hyposalivation, evaluated by a screening 5. Unstimulated salivary flow rate between 0.2mL/min and 0.05mL/min 6. Grade 2-3 xerostomia (CTCAEv5.0) 7. WHO Performance status (PS) 0-1 8. Informed consent
Exclusion criteria
1. Any cancer in the previous 4 years (not including OPSCC and basocellular carcinomas) 2. Xerogenic medications 3. Penicillin or Streptomycin allergy 4. Any other diseases of the salivary glands, e.g. Sjögren's syndrome or sialolithiasis 5. Previous parotid or submandibular gland surgery 6. Previous treatment with any type of stem cells 7. Breastfeeding, Pregnancy or planned pregnancy within the next 2 years 8. Smoking within the previous 6 months. 9. Alcohol abuse (consumption must not exceed 7 units/week for women and 14 units/week for men (Danish National board health alcohol guidelines3) 10. Any other disease/condition judged by the investigator to be grounds for exclusion
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety: Number of patients with serious adverse events | 4 months | Registration of number of patients with serious adverse events in a 4 months follow-up period |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy: Change in Unstimulated Whole Salivary flow rate | 4 months | Unstimulated whole saliva flow rate is assessed by sialometry |
| Efficacy: Change in Stimulated Whole Salivary flow rate | 4 months | Unstimulated whole saliva flow rate is assessed by sialometry |
| Efficacy: Change in quality of life | 4 months | Change in quality of life evaluted by QLQ-H&N-35 and XQ questionnaires |
| Efficacy: Salivary gland function | 4 months | Assessed by salivary gland 99mTc scintigraphy |
| Immune reponse :Development of donor specific antibodies | 4 months | Registration of development of tissue antibodies towards donor cells |
| Efficacy: Change in Saliva Proteomics | 4 months | Change in Saliva proteomics |
| Efficacy: Change in RNA in Saliva | 4 months | Change in RNA in saliva |
| Immune reponse | 4 months | Reactions in plasma and saliva will be assessed |
| Efficacy: Change in Saliva composition | 4 months | Change in inorganic saliva composition |
Countries
Denmark
Outcome results
None listed