Intraglandular Treatment with Adipose-derived Mesenchymal Stem Cells in Patients with Xerostomia Due to Sjögren's Disease (ASSIX)

Intraglandular Treatment with Adipose-derived Mesenchymal Stem Cells in Patients with Xerostomia Due to Sjögrens Disease

Living with dry mouth significantly impacts daily life, causing constant discomfort. It makes it harder to talk, eat solid food (increasing the risk of malnutrition), swallow, and sleep well. It also raises the risk of tooth decay. One common cause of dry mouth is Sjögren's Syndrome.

Sjögren's Syndrome is a common chronic autoimmune disease. In this disease, the immune system attacks the body's own saliva glands, reducing saliva production and leading to severe dry mouth and its associated symptoms.

Current treatments for dry mouth are temporary and only last a short time (from a few minutes to a few hours). Therefore, new treatment options are needed.

Research has shown that mesenchymal stem cells can be used to treat dry mouth with promising results. These stem cells can be injected into a vein or directly into the saliva glands. Although the exact mechanism is not fully understood, studies suggest that stem cells can positively affect the immune system, reduce inflammation, regenerate tissue, and reverse scarring.

This research group has been studying stem cell treatment for dry mouth for over 10 years and is internationally recognized. The group have conducted three studies where we injected stem cells into the saliva glands of patients with dry mouth due to radiation therapy for head or neck cancer. Results showed a 30%-50% increase in saliva production and a significant reduction in dry mouth symptoms. No studies have yet investigated injecting stem cells into the saliva glands of patients with dry mouth due to Sjögren's Syndrome. One study did inject stem cells into tear glands with promising results. Therefore, this study aim to investigate injecting stem cells into the saliva glands of patients with dry mouth due to Sjögren's Syndrome.

For this study, mesenchymal stem cells harvested from the fat tissue of healthy adult donors is used. This type of stem cell is better at reversing scarring and forming new blood vessels. The procedure is quick and has few side effects, and donors benefit from the fat removal. The fat is typically taken from the abdominal area. Donors are tested for various diseases to ensure they are healthy. Previous studies have shown that the treatment is safe with only a few temporary side effects.

The hypothesis is that injecting stem cells into the saliva glands of patients with dry mouth due to Sjögren's Syndrome will improve saliva production and reduce dry mouth symptoms. The study aims to determine if this treatment increases saliva production and reduces symptoms caused by dry mouth.

To test these hypotheses, the study will include:

1. The treatment itself with either stem cells or a placebo (sterile saline).
2. Multiple saliva tests to measure saliva production.
3. Saliva samples stored for later analysis to see if the saliva's ability to protect teeth and aid digestion changes after stem cell treatment.
4. A blood test to examine the immune system's response to the stem cell treatment.
5. A clinical examination to see if the stem cell treatment affects Sjögren's Syndrome symptoms elsewhere in the body.
6. Questionnaires to assess participants' perceptions of changes in dry mouth symptoms after treatment.

The treatment involves injecting either stem cells or a placebo into the two saliva glands near the jaw, guided by an ultrasound scan. The procedure takes 10 minutes.

Although stem cell treatment has been shown to be safe, safety will be monitored in this study. At all three visits, participants will be asked about any side effects, which will be categorized as serious or mild, and as treatment-related or not. Follow-up and treatment plans will be made for any side effects. Participants will also always have direct access to the treating doctor.

The study will be monitored by the Danish Medicines Agency and the GCP unit, which ensures that all rules and laws are followed.

Study Overview

• Status: Recruiting
• Conditions: Sjorgren's Syndrome
• Intervention / Treatment: Drug: Saline Water (Control); Drug: MSC

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 2; Phase 1

Contacts and Locations

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

Study Locations

• Denmark
  • Copenhagen, Denmark, 2100
    • Recruiting
    • Rigshospitalet
    • Contact: Joachim Hansen, M.D PhD-fellow; Phone Number: +4523312552; Email: joachim.hansen.01@regionh.dk
    • Contact: Joachim Hansen, M.D PhD-fellow

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Patients diagnosed with SS according to the American College of Rheumatology/European League Against Rheumatism (ACR-EULAR) classification criteria for primary SjD (2)
2. Age equal or above 18 years
3. Persistent xerostomia for at least 3 months
4. Unstimulated whole saliva flow rate (UWS) of minimum 0.05 ml/min and maximum 3.0 ml/min
5. Capable and willing to receive proper information and to give written informed consent.

Exclusion Criteria:

1. Current intake of xerogenic medications such as anticholinergics, tricyclic antidepressants, opioids, and certain antihypertensive agents (23)
2. Presence of any other diseases of the salivary glands, e.g. xerostomia due to radiation
3. Previous submandibular gland surgery
4. Previous treatment with any type of stem cells in the salivary glands
5. Pregnancy or planned pregnancy within the 12 months study period
6. Breastfeeding
7. Tobacco smoking within the previous 6 months from screening visit
8. Have a current alcohol abuse (consumption must not exceed 10 units per week (Danish National board health alcohol guidelines (24))
9. Any other disease/condition judged by the investigator to be grounds for exclusion

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
Placebo Comparator: Placebo; Isotone sterile saline water	Drug: Saline Water (Control); Isotonic sterile saline water
Experimental: MSC; Allogeneic adipose-derived stem / stromal cells in 10% DMSO	Drug: MSC; Allogeneic adipose-derived mesenchymal stromal / stem cells in 10% DMSO

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in unstimulated whole saliva flow rate by sialometry	From baseline to 4 months after treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in stimulated whole saliva flow rate by sialometri		From baseline to 4 and 12 months after treatment
• Safety evaluated by number of serious adverse events (SAE), adverse advents (AE), and deaths		From baseline to 4 and 12 months after treatment
Quality of the whole saliva measured as changes in percentages in the concentration of electrolytes, total protein, alpha-amylase, and salivary IgA with Elisa assays	The concentrations of the specific electrolyte, total protein and IgA will be compared to reference values.	From baseline to 4 and 12 months after treatment
Immune response measured by the development of donor specific antibodies	Serum will be frozen until the end of the trial and all samples will be analyzed together. The blood samples will be analyzed for HLA class I and class II antibodies with the Luminex platform (Luminex 200 system or LABScan3D) and will be reported as HLA antibodies present/not present in the samples.	From baseline to 4 and 12 months after treatment
Lacrimal secretion measured by the Schirmers Test		From baseline to 4 and 12 months after treatment
• Changes in the gland morphology as assessed by ultrasound	Measured as changes in the OMERACT US system	From baseline to 4 and 12 months after treatment
• Changes in ESSDAI		From baseline to 4 and 12 months after treatment
• Changes in ESSPRI		From baseline to 4 and 12 months after treatment
PROM: Xerostomia Questionnaire	This PROM will be compared by converting to summary-scores ranging from 0-100.	From baseline to 4 and 12 months after treatment
PROM:Clinical Oral Dryness score.	This outcome will be compared by converting to summary-scores ranging from 0-100	From baseline to 4 and 12 months after treatment
PROM: Summated Xerostomia Inventory.	This outcome will be compared by converting to summary-scores ranging from 0-100	From baseline to 4 and 12 months after treatment

Collaborators and Investigators

• Sponsor: Rigshospitalet, Denmark

Study record dates

Study Major Dates

• Study Start (Actual): January 21, 2025
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: January 21, 2025
• First Submitted That Met QC Criteria: January 27, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 27, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: MSC; Sjogren's syndrome; xerostomia; dry mouth; Sjogren's disease; Mesenchymal stem/stromal cell; randomized clinical trial (RCT); Advanced Therapy Medicinal Product (ATMP),
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Mouth Diseases; Stomatognathic Diseases; 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; Sjogren's Syndrome; Xerostomia
• Other Study ID Numbers: EU CT: 2024-516715-25-00; 2024-516715-25-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Access to participant level-data and statistical code can be granted through a reasonable request to the corresponding author and subsequent approval from the relevant authorities.

IPD Sharing Time Frame

Full protocol in available through CTIS (https://euclinicaltrials.eu/).

IPD will be available after last patient's last visit

• IPD Sharing Access Criteria: Access to participant level-data and statistical code can be granted through a reasonable request to the corresponding author and subsequent approval from the relevant authorities.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Study Data/Documents

1. Study Protocol
   Information identifier: 2024-516715-25-00

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No