Allogeneic Mesenchymal Stem Cells for Radiation-induced Hyposalivation and Xerostomia/Dry Mouth

Phase 1

Active, not recruiting

• Conditions: Mesenchymal Stromal Cells; Stem Cells; Xerostomia Due to Radiotherapy; Hyposalivation; Dry Mouth; Mesenchymal Stem Cells; Xerostomia; Oropharynx Cancer; Salivary Gland Diseases
• Interventions: Biological: Allogeneic adipose derived stem/stromal cells

• Registration Number: NCT03874572
• Lead Sponsor: Rigshospitalet, Denmark

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.

Study Timeline

• Study First Submitted: 2019-03-12
• Study First Submitted QC: 2019-03-12
• Study First Posted: 2019-03-14
• Study Start: 2019-03-18
• Primary Completion: 2020-06-22
• Status Verified: 2020-09
• Last Update Submitted: 2021-01-27
• Last Update Posted: 2021-01-29
• Study Completion: 2025-12-01

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 10

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Allogeneic mesenchymal stem/stromal cell therapy	Allogeneic adipose derived stem/stromal cells	Treatment with intra-glandular Injections of allogeneic adipose derived stem cells

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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: Change in Saliva composition	4 months	Change in inorganic saliva composition
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
Immune reponse :Development of donor specific antibodies	4 months	Registration of development of tissue antibodies towards donor cells
Efficacy: Change in Unstimulated Whole Salivary flow rate	4 months	Unstimulated whole saliva flow rate is assessed by sialometry
Efficacy: Salivary gland function	4 months	Assessed by salivary gland 99mTc scintigraphy

Trial Locations

Locations (2)

Department of Otolaryngology, Rigshospitalet, University Hospital of Copenhagen; 🇩🇰 Copenhagen, Denmark

Department of Otolaryngology, Rigshospitalet; 🇩🇰 Copenhagen, Denmark