Safety and Efficacy of Mesenchymal Stem Cell for Radiation-induced Hyposalivation and Xerostomia in Previous Head and Neck Cancer Patients

NCT04776538 | Unknown Phase 2 DMC

• 1 other identifier: CVB2018-1
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

The incidence of head and neck cancer is increasing in the Western World, including Denmark. Cancer of the head and neck and its treatment often have a detrimental and lifelong impact on the quality of life of the patients. Radiotherapy is a key component for approximately 80% of all patients with head and neck cancer and despite the enormous improvement in ionizing radiotherapy, the radiation still leads to significant ionizing of healthy tissue, including the radiation-sensitive salivary glands. Salivary glands suffer severe damage from radiation, and as these cells are the principal sites of fluid secretion one of the most prevalent side effect of irradiation for head and neck cancer is hyposalivation and dry mouth syndrome, xerostomia. Xerostomia leads to debilitating oral disorders and major implication for the overall quality of life, including social life and professional life. Currently, only symptomatic treatment is available to patients suffering from xerostomia, and therefore there is an immense, unmet need for new treatment strategies for hyposalivation and xerostomia. Stem cells have been identified as a potential treatment modality for a wide variety of disorders by their ability to differentiate into many functional cell types, and stem cells have been suggested as an approach to restoring the function of salivary glands after radiotherapy damage. The purpose of the study is to assess the efficacy and safety of the injection of stem cells from healthy donors on radiation-induced salivary gland hypofunction and xerostomia in previous head and neck cancer patients. The project can potentially help to develop a clinically relevant treatment option for the growing number of patients suffering from xerostomia after irradiation. The development of new therapies is especially meaningful since only sub-optimal, symptomatic treatments are currently available, and since the symptom of xerostomia immensely reduces quality of life.

Conditions

Xerostomia Following Radiotherapy

Keywords

stem cell; Adipose derived stem cell

Outcome Measures

Primary Outcomes (1)

• Salivary gland function

  Change in salivary gland function measured by a 4 months change in unstimulated whole saliva flow rate in the group receiving ASCs compared with the group of participants receiving placebo (control group receiving injections of CryoStor10 (BiolifeSolutions), the freeze media for ASCs).

  4 month

Secondary Outcomes (14)

• Incidence of treatment-emergent adverse events

  4 month

• Patient-Reported Outcome of xerostomia

  4 month

• Patient-Reported Outcome of xerostomia

  4 month

• Salivary composition

  4 month

• Salivary composition

  4 month

Study Arms (2)

Stem cell group

EXPERIMENTAL

60 patients will be randomized to receive adipose-derived allogeneic stem cells

Biological: Stem cells

Placebo group

PLACEBO COMPARATOR

60 patients will receive placebo consisting of CryoStor10 (BiolifeSolutions), the freeze media for ASCs containing 10% Dimethyl sulfoxide (DMSO).

Biological: Placebo

Interventions

Stem cells BIOLOGICAL

Each participant will be double-blindly randomized to receive either adipose-derived allogeneic stem cells or placebo consisting of CryoStor10 (BiolifeSolutions), the freeze media for ASCs containing 10% Dimethyl sulfoxide (DMSO).

Stem cell group

Placebo BIOLOGICAL

Each participant will be double-blindly randomized to receive either adipose-derived allogeneic stem cells or placebo consisting of CryoStor10 (BiolifeSolutions), the freeze media for ASCs containing 10% Dimethyl sulfoxide (DMSO).

Placebo group

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age between 18-70 years
• Previous radiotherapy +/- chemotherapy for head and neck cancer 2 years' follow-up without recurrence
• Clinically reduced salivation and hyposalivation, evaluated by a screening
• Unstimulated salivary flow rate between 0.2 milliliter(mL)/minut (min) and 0.05 mL/min
• Grade 1-3 xerostomia as evaluated by the UKU side effect rating scale
• World Health organization (WHO) Performance status (PS) 0-1 59
• Informed consent

You may not qualify if:

• Any cancer in the previous 4 years (not including the head and neck cancer and basocellular carcinomas)
• Xerogenic medications
• Penicillin or Streptomycin allergy
• Any other diseases of the salivary glands, e.g. Sjögren's syndrome or sialolithiasis
• Previous submandibular gland surgery
• Previous treatment with any type of stem cells in the saliva glands
• Pregnancy or planned pregnancy within the four months study period
• Breastfeeding
• Smoking within the previous 6 months.
• Alcohol abuse (consumption must not exceed 7 units/week for women and 14 units/week for men (Danish National board health alcohol guidelines)

Sponsors & Collaborators

• Rigshospitalet, Denmark: lead
• Cardiology Stem Cell Centre, The Heart Centre, Rigshospitalet: collaborator
• Department of Oncology Herlev Hospital, Denmark: collaborator
• Department of Dentistry and Oral Health, Aarhus, Denmark: collaborator

Study Sites (1)

Christian von Buchwald, MD, DMSc, Professor

Copenhagen, 2100, Denmark

Location

Related Publications (2)

• Carlander AF, Jakobsen KK, Jersie-Christensen R, Hansen J, Bendtsen SK, Kastrup J, Belstrom D, Lynggard CD, Gronhoj C, von Buchwald C. 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. Trials. 2025 Nov 28;26(1):554. doi: 10.1186/s13063-025-09074-4.

  PMID: 41316394 DERIVED

• Jakobsen KK, Carlander AF, Gronhoj C, Todsen T, Melchiors J, Paaske N, Madsen AKO, Kastrup J, Ekblond A, Haack-Sorensen M, Farhadi M, Maare C, Friborg J, Lynggard CD, von Buchwald C. Effectiveness and safety of mesenchymal stem/stromal cell for radiation-induced hyposalivation and xerostomia in previous head and neck cancer patients (MESRIX-III): a study protocol for a single-centre, double-blinded, randomised, placebo-controlled, phase II study. Trials. 2023 Sep 1;24(1):567. doi: 10.1186/s13063-023-07594-5.

  PMID: 37658468 DERIVED

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: The sponsor, investigators, study staff (except for staff involved in stem cells preparation and staff involved in bioanalytical analyses) and patients will be blinded to treatment assignment and care will be taken to ensure the study team is kept blinded.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Doctor, investigator

Model Details: The study is a prospective, double-blinded, randomized, placebo-controlled trial

Study Record Dates

• First Submitted: January 21, 2021
• First Posted: March 1, 2021
• Study Start: February 9, 2021
• Primary Completion: March 1, 2024
• Study Completion: March 1, 2024
• Last Updated: September 14, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)