Efficacy and Safety of Allogenic Cultured Adipose-derived Mesenchymal Stromal Cell Injections on MoUth Fibrosis and Handicap in Patients With Systemic sclEroderma (A-MUSE)

Orofacial manifestations and microstomia are a frequent complication in systemic sclerosis (SSc) with a major impact on oral hygiene, dental care and quality of life. Peri-oral injection of allogeneic cultured adipose-derived stromal cells constitutes a promising approach to treat scleroderma-induced mouth fibrosis where no alternative therapy is validated. The aim of this phase 2 study is to compare efficacy and safety of perioral injection of allogeneic cultured adipose-derived stromal cells (AdMSC) versus placebo to improve oro-facial fibrosis in patients with systemic sclerosis.

Study Overview

• Status: Not yet recruiting
• Conditions: Systemic Scleroderma
• Intervention / Treatment: Drug: AdMSC; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Gregory PUGNET, MD, PHD; Phone Number: 0561323954; Email: pugnet.g@chu-toulouse.fr
• Study Contact Backup: Name: Charline DAGUZAN; Phone Number: 0561778490; Email: daguzan.c@chu-toulouse.fr

Study Locations

• France
  • Bordeaux, France
    • Bordeaux Hospital
    • Principal Investigator: Marie-Elise TRUCHETET
    • Contact: Marie-Elise TRUCHETET; Phone Number: 0556794919; Email: marie-elise.truchetet@chu-bordeaux.fr
  • Dijon, France
    • Dijon Hospital
    • Contact: Martin NIVET; Phone Number: 04380293432; Email: martin.nivet@chu-dijon.fr
    • Principal Investigator: Martin NIVET
  • Montpellier, France
    • Montpellier Hospital
    • Contact: Alexandre MARIA; Phone Number: 0467336733; Email: a-maria@chu-montpellier.fr
    • Principal Investigator: Alexandre MARIA
  • Nantes, France
    • Nantes Hospital
    • Contact: Christian AGARD; Phone Number: 0240083379; Email: christian.agard@chu-nantes.fr
    • Principal Investigator: Christian AGARD
  • Toulouse, France
    • Toulouse Hospital
    • Principal Investigator: Gregory Pugnet
    • Contact: Gregory PUGNET; Phone Number: 0561322077; Email: pugnet.g@chu-toulouse.fr

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Male or female patient ≥18 years of age,
• Patient with systemic scleroderma according to the 2013 ACR/EULAR classification criteria,
• Mouth Handicap in Systemic Sclerosis Scale (MHISS) score more than or equal to 20 (0-48),
• Rodnan skin score on the face more than or equal to 1,
• Maximal mouth opening of less than 40 mm (distance between the dental arches)
• Patient must have provided written informed consent prior to enrolment,
• Patient must be able to understand their requirements of participating in the protocol.
• Patient affiliated to a social security system.

Exclusion Criteria:

• Patient participating in a clinical trial or having participated in a clinical trial within the previous 3 months,
• Injection of botulinum toxin within 4 weeks prior to "inclusion visit",
• Patient who underwent autologous hematopoietic stem cell transplantation (HSCT) within less than 1 year,
• Local active labial herpes virus within 1 week prior to "inclusion visit",
• Patients with an indication for intensification by autologous HSCT (according to EBMT guidelines and national MATHEC-SFGMTC guidelines),
• History of cancer in the last five years, except for successfully excised basal cell/squamous cell carcinoma, or successfully excised early melanoma of the skin. Subjects, who had a successful tumor resection or radiation or chemotherapy more than 5 years prior to inclusion and no recurrence, may be enrolled in the study,
• Radio- or chemotherapy in progress,
• Females who are pregnant or breastfeeding or plan to be or do so during the course of this study,
• Women of childbearing potential (WOCBP) who are sexually active and unwilling to use an adequate birth control method,
• Vulnerable patient (persons deprived of their liberty by judicial or administrative decision, persons undergoing psychiatric treatment, persons admitted to a health or social establishment for purposes other than research) according to article L1121-6 of the Public Health Code

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
Experimental: AdMSC; Patients will be standard of care (physiotherapy and daily self-administered exercises) and receive allogeneic AdMSC injection in the perioral (lips) region.	Drug: AdMSC; At day 0, patients will have AdMSC injections in perioral region. Patients will be followed-up for 24 weeks
Placebo Comparator: Placebo; Patients will be standard of care (physiotherapy and daily self-administered exercises) and receive placebo injections in the perioral (lips) region	Drug: Placebo; At day 0, patients will have placebo injections in perioral region. Patients will be followed-up for 24 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in the Mouth Handicap in Systemic Sclerosis scale (MHISS)	the change in the Mouth Handicap in Systemic Sclerosis scale (MHISS) between baseline and week 12. An improvement of at least 5 points will be considered clinically significant	Day 0, 12 weeks after injection

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety of treatment	The safety throughout the course of the study (until week 24 since baseline) will be assessed by monitoring adverse events, serious adverse events and injection site reactions.	Day 0, 4, 12 and 24 weeks after injection
Efficacy on oral function by facial scanners	Efficacy on oral function is a composite measure derived from the change in maximum interincisal distance and mouth perimeter by facial scanners with digital acquisition of the patient's face in just a few seconds	Day 0, 4, 12 and 24 weeks after injection
Efficacy on orofacial handicap	Efficacy on orofacial handicap is a composite measure derived from change in Opening, Dryness and Aesthetic the 3 subscales of the MHISS	Day 0, 4, 12 and 24 weeks after injection
Patient satisfaction	the patients will be asked to fill in a simple questionnaire where their degree of satisfaction could be expressed by a composite measure derived by a semiquantitative score (unsatisfied, mildly/moderately satisfied, rather satisfied, and very satisfied), Scleroderma Health Assessment Questionnaire (sHAQ), Oral Health Assessment Tool (OHAT), Burden of Face Affected questionnaire (BOFA) and EQ-5D-5L	Day 0, 4, 12 and 24 weeks after injection
Oral habits and hygiene	Change in oral habits and hygiene is a composite measure derived from oral health and hygiene questionnaire	Day 0 and 24 weeks after injection
oral microbiota	Change in oral microbiota mesuared in unstimulated saliva	Day 0, 12 and 24 weeks after injection
Plaque index	Change in Plaque index (reflecting the ability to maintain oral hygiene)	Day 0, 12 and 24 weeks after injection
Change in decayed missing filled teeth	Change in decayed missing filled teeth (DMFT) index : a commonly used index validated by the WHO to assess oral status and the examinator simply counts the number of decayed, missing (due to caries or periodontal disease) and restored/filled teeth.	Day 0 and 24 weeks after injection
Change in mandibular tracking	Change Mandibular tracking is a composite measure derived from mandibular tracking and articular and neuro-muscular activity. Mandibular tracking and neuro-muscular activity will be measured with electrodes positioned in order to assess muscular activity at rest, muscle activity during mouth closure as well as during extreme movement of mouth opening and closing, mandibular propulsion and deduction. Muscle contraction synchronism and contraction efficacy will also be measured as well as the 3-dimensional innoclusion space and mandibular movement during swallowing	Day 0, 4, 12 and 24 weeks after injection
Posture by stabilometry	Change posture by stabilometry	Day 0, 12 and 24 weeks after injection
psycho-social aspects and oro-facial pains	Change in psycho-social aspects and oro-facial pains is a composite measure derived from EDAS21, Epworth and Combadazou-Destruhaut questionnaire	Day 0, 4, 12 and 24 weeks after injection
Rodnan skin score	Change in modified Rodnan skin score	Day 0, 12 and 24 weekds after injection
Dry mouth syndrome	Change in dry mouth syndrome is a composite measure derived from the change in Xerostomia Inventory questionnaire , in salivary flow, in the salivary pH and Salivary pH	Day 0, 4, 12 and 24 weeks after injection
Efficacy on aesthetics	the efficacy on aesthetics assessed by Standardized two-dimensional photographs or face scan	Day 0, 4 , 12 and 24 weeks after injection
Immunomonitoring of vascular and antifibrotic biomarkers	Immunomonitoring of vascular and antifibrotic biomarkers (V5. Endothelin-1, Endostatin, Endogline, Angiotensin I and II, Tie 1 and 2, VEGF, sICAM-1, sVCAM, E-selectin, CXCL4) measured in blood samples	Day 0 and 12 weekds after injection

Collaborators and Investigators

• Sponsor: University Hospital, Toulouse

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2026
• Primary Completion (Estimated): April 30, 2028
• Study Completion (Estimated): July 31, 2028

Study Registration Dates

• First Submitted: December 4, 2025
• First Submitted That Met QC Criteria: December 23, 2025
• First Posted (Actual): January 8, 2026

Study Record Updates

• Last Update Posted (Actual): January 8, 2026
• Last Update Submitted That Met QC Criteria: December 23, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: regenerative medicine; Systemic Scleroderma; oral pathology; microstomia; oral health-related quality of life; allogenic cultured adipose-derived stromal cells
• Additional Relevant MeSH Terms: Mouth Diseases; Stomatognathic Diseases; Connective Tissue Diseases; Skin Diseases; Stomatognathic System Abnormalities; Congenital Abnormalities; Mouth Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Skin and Connective Tissue Diseases; Scleroderma, Systemic; Microstomia
• Other Study ID Numbers: RC31/22/0258; 2024-518516-39-00 (Ctis)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No