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

Rigshospitalet

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Sjorgren's Syndrome

Treatments: Drug: Saline Water (Control); Drug: MSC

Study type: Interventional

Funder types: Other

Identifiers

NCT06805448

2024-516715-25-00 (EU Trial (CTIS) Number)

EU CT: 2024-516715-25-00

Details and patient eligibility

About

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.

Enrollment: 40 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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40 participants in 2 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

Isotone sterile saline water

Treatment:

Drug: Saline Water (Control)

MSC

Experimental group

Description:

Allogeneic adipose-derived stem / stromal cells in 10% DMSO

Treatment:

Drug: MSC