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Safety and Potential Effect of Innovative Cell-based Therapy Using Adipose-derived Stromal Vascular Fraction in Patients With Autoimmune Xerostomia (XEROCELL)

Primary Purpose

Xerostomia

Status
Not yet recruiting
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
lipoaspiration
Injection of the autologous adipose-derived stromal vascular fraction (AD-SVF)
Sponsored by
Assistance Publique Hopitaux De Marseille
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Xerostomia

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Patients from 18 to 65 years. Patients suffering from xerostomia and autoimmune disease including : Gougerot-Sjögren disease according to AC/EULAR criteria and Secondary Gougerot-Sjögren syndrome related to systemic diseases (sclerodermia, rheumatoid arthritis, systemic lupus erythematosus...) Xerostomia visual scale (6-item visual analogue scale questionnaire) for assessment of salivary dysfunction : score ≥ 30/60 Informed consent to participate (with signature) Negative β -HCG test and effective contraception for women being able to get pregnant Affiliation to the social security system Exclusion Criteria: Medical history of head and neck neoplasia Recent (<3 months) medication inducing and aggravating xerostomia : Standard treatment with tricyclic antidepressant and/or antipsychotics Body Mass Index < 18 Active smoking (> 5 cigarettes a day) Active infectious disease and/or active viral serologies (HIV, HCV, HBV, HTLV I/II, TPHA/VDRL) Coagulation disorders including anticoagulant and antiplatelet treatment Any temporary or definitive contraindication due to any medical or surgical unstable condition Allergy to local anesthesia and/or albumin Pregnant or breastfeeding women Adult protected by the law (tutorship and curatorship) Patients already enrolled in another study Patients under 18 years of age Person deprived of liberty Patient non-affiliated to the social security

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    Adult patients suffering from xerostomia and autoimmune disease

    Arm Description

    Xerostomia treatment consist of 3 steps (including 2 surgical steps) in the Hospital de la Conception of Marseille, in the same ward : The plastic/maxillofacial surgeon : collects the adipose tissue, and transfers it to the cell therapy unit; The cell therapy unit processes and controls the experimental product (adipose-derived stromal vascular fraction; AD-SVF) from the harvested adipose tissue. The AD-SVF batch is nominatively transported to the surgeon; The maxillofacial surgeon injects the AD-SVF without delay under local anesthesia.

    Outcomes

    Primary Outcome Measures

    Intensity of adverse reactions at the injection site at day 1
    1 day after ADSVF injection, a subjective evaluation will be done by the patient of lip sensibility, pain, oedema or ecchymosis bleeding or haematoma, bleeding or haematoma, other event through an adapted report form with phone assessment
    Intensity of adverse reactions at the injection site at day 3
    3 days after ADSVF injection, a subjective evaluation will be done by the patient of lip sensibility, pain, oedema or ecchymosis bleeding or haematoma, bleeding or haematoma, other event through an adapted report form with phone assessment.
    Intensity of adverse reactions at the injection site at day 7
    7 days after ADSVF injection, a subjective evaluation will be done by the patient of lip sensibility, pain, oedema or ecchymosis bleeding or haematoma, bleeding or haematoma, other event through an adapted report form with clinical assessment.
    Intensity of adverse reactions at the injection site at day 14
    14 days after ADSVF injection, a subjective evaluation will be done by the patient of lip sensibility, pain, oedema or ecchymosis bleeding or haematoma, bleeding or haematoma, other event through an adapted report form with clinical assessment.
    Intensity of adverse reactions at the harvesting site at day 1
    1 day after ADSVF injection, a subjective evaluation will be done by the patient of pain, oedema or ecchymosis bleeding or haematoma, inflammation or infection, other event through an adapted report form with phone assessment.
    Intensity of adverse reactions at the harvesting site at day 3
    3 days after ADSVF injection, a subjective evaluation will be done by the patient of pain, oedema or ecchymosis bleeding or haematoma, inflammation or infection, other event, through an adapted report form with phone assessment.
    Intensity of adverse reactions at the harvesting site at day 7
    7 days after ADSVF injection, a subjective evaluation will be done by the patient of pain, oedema or ecchymosis bleeding or haematoma, inflammation or infection, other event, through an adapted report form with clinical assessment.
    Intensity of adverse reactions at the harvesting site at day 14
    14 days after ADSVF injection, a subjective evaluation will be done by the patient of pain, oedema or ecchymosis bleeding or haematoma, inflammation or infection, other event through an adapted report form with clinical assessment.

    Secondary Outcome Measures

    Intensity of adverse reactions at the injection site at day 15
    15 days after ADSVF injection, a subjective evaluation will be done by the patient of lip sensibility, pain, oedema or ecchymosis bleeding or haematoma, bleeding or haematoma, other event through an adapted report form with clinical assessment.
    Intensity of adverse reactions at the injection site at month 1
    1 month after ADSVF injection, a subjective evaluation will be done by the patient of lip sensibility, pain, oedema or ecchymosis bleeding or haematoma, bleeding or haematoma, other event through an adapted report form with clinical assessment.
    Intensity of adverse reactions at the injection site at month 3
    3 months after ADSVF injection, a subjective evaluation will be done by the patient of lip sensibility, pain, oedema or ecchymosis bleeding or haematoma, bleeding or haematoma, other event through an adapted report form with clinical assessment.
    Intensity of adverse reactions at the injection site at month 6
    6 months after ADSVF injection, a subjective evaluation will be done by the patient of lip sensibility, pain, oedema or ecchymosis bleeding or haematoma, bleeding or haematoma, other event through an adapted report form with clinical assessment.
    Intensity of adverse reactions at the injection site at month 7
    7 months after ADSVF injection, a subjective evaluation will be done by the patient of lip sensibility, pain, oedema or ecchymosis bleeding or haematoma, bleeding or haematoma, other event through an adapted report form with clinical assessment.
    Intensity of adverse reactions at the harvesting site at day 15
    15 days after ADSVF injection, a subjective evaluation will be done by the patient of pain, oedema or ecchymosis bleeding or haematoma, inflammation or infection, other event through an adapted report form with clinical assessment.
    Intensity of adverse reactions at the harvesting site at month 1
    1 month after ADSVF injection, a subjective evaluation will be done by the patient of pain, oedema or ecchymosis bleeding or haematoma, inflammation or infection, other event through an adapted report form with clinical assessment.
    Intensity of adverse reactions at the harvesting site at month 3
    3 months after ADSVF injection, a subjective evaluation will be done by the patient of pain, oedema or ecchymosis bleeding or haematoma, inflammation or infection, other event through an adapted report form with clinical assessment.
    Intensity of adverse reactions at the harvesting site at month 6
    6 months after ADSVF injection, a subjective evaluation will be done by the patient of pain, oedema or ecchymosis bleeding or haematoma, inflammation or infection, other event through an adapted report form with clinical assessment.
    Intensity of adverse reactions at the harvesting site at month 7
    7 months after ADSVF injection, a subjective evaluation will be done by the patient of pain, oedema or ecchymosis bleeding or haematoma, inflammation or infection, other event through an adapted report form with clinical assessment.
    primary efficiency of AD-SVF iin term of glands reparation process/repair (Minor salivary gland biopsy)
    A minor salivary gland biopsy will be done under local anaesthesia 6 months after the injection. Then, an Histological analysis (4 grades Chilson-Mason score) of minor salivary gland biopsy will be performed.
    efficacy of AD-SVF at month 1
    Salivary flow will be collected after stimulation 1 month after the injection. It is expressed in milliliter by minutes after 5 minutes of collect, and oligoptyalism isdefined by a salivary flow < 0.1 mL/mn at rest, and < 0.7 ml/mn after stimulation.
    efficacy of AD-SVF at month 3
    Salivary flow will be collected after stimulation 3 months after the injection. It is expressed in milliliter by minutes after 5 minutes of collect, and oligoptyalism isdefined by a salivary flow < 0.1 mL/mn at rest, and < 0.7 ml/mn after stimulation.
    efficacy of AD-SVF at month 6
    Salivary flow will be collected after stimulation 6 months after the injection. It is expressed in milliliter by minutes after 5 minutes of collect, and oligoptyalism isdefined by a salivary flow < 0.1 mL/mn at rest, and < 0.7 ml/mn after stimulation.
    Change in dryness of oral mucosa
    Change in dryness of oral mucosa will be assessed from Clinical Oral Dryness Score (CODS) based on 10 items realized before and, 3 and 6 months after the injection.
    Change in xerostomia Visual Analogic Scale (VAS)
    Change in VAS will be assessed from a 6-items questionnaire scored from 0 to 10 (increasing gravity) according to Likert scale.

    Full Information

    First Posted
    April 14, 2023
    Last Updated
    May 22, 2023
    Sponsor
    Assistance Publique Hopitaux De Marseille
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05857358
    Brief Title
    Safety and Potential Effect of Innovative Cell-based Therapy Using Adipose-derived Stromal Vascular Fraction in Patients With Autoimmune Xerostomia
    Acronym
    XEROCELL
    Official Title
    Safety and Potential Effect of Innovative Cell-based Therapy Using Adipose-derived Stromal Vascular Fraction in Patients With Autoimmune Xerostomia (XEROCELL)
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    April 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    September 2023 (Anticipated)
    Primary Completion Date
    October 2026 (Anticipated)
    Study Completion Date
    April 2027 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Assistance Publique Hopitaux De Marseille

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    The main objective of this study is to evaluate the tolerance and safety of autologous adipose-derived stromal vascular fraction injected in accessory salivary glands for treatment of autoimmune xerostomia in terms of adverse reactions through day 14 (D14).
    Detailed Description
    Autoimmune xerostomia is a disabling condition affecting mostly patients suffering from Sjögren's disease, systemic lupus erythematosus, rheumatoid arthritis and systemic xerostomia. Local therapies and systemic drug treatments (picarpine) remain the gold standards but have limited effects upon salivary flow action and many adverse effects. Stem cell therapies and notably adipose tissue-derived stromal cells have shown promising potential for tissue repair. Autologous uncultured adipose-derived stromal vascular fraction (AD-SVF) is recognized as an easily accessible (by a standard lipoaspiration to obtain adipose tissue, from which AD-SVF are isolated by centrifugation), safe and well tolerated source of cells with angiogenic, anti-inflammatory, immunomodulatory and regenerative properties. The purpose of our AD-SVF phase I trial is to evaluate, first the tolerance of autologous AD-SVF cells locally injected in the oral cavity and second their capability to improve the salivary function.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Xerostomia

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 1, Phase 2
    Interventional Study Model
    Single Group Assignment
    Masking
    None (Open Label)
    Allocation
    N/A
    Enrollment
    18 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Adult patients suffering from xerostomia and autoimmune disease
    Arm Type
    Experimental
    Arm Description
    Xerostomia treatment consist of 3 steps (including 2 surgical steps) in the Hospital de la Conception of Marseille, in the same ward : The plastic/maxillofacial surgeon : collects the adipose tissue, and transfers it to the cell therapy unit; The cell therapy unit processes and controls the experimental product (adipose-derived stromal vascular fraction; AD-SVF) from the harvested adipose tissue. The AD-SVF batch is nominatively transported to the surgeon; The maxillofacial surgeon injects the AD-SVF without delay under local anesthesia.
    Intervention Type
    Procedure
    Intervention Name(s)
    lipoaspiration
    Intervention Description
    Adipose tissue harvest will be conducted by a surgeon under under local and intra-veinous sedation anesthesia. Once the patient is asleep and just before the laying of the operating drapes, the skin will be thoroughly disinfected, in order to avoid bacteriological contamination. Each entry point will be disinfected with betadine before and regularly during the procedure and will receive local anesthesia. The lipoaspiration sites will be infiltrated using a closed system, thanks to a Khoury canula. Adipose tissue will be harvested after waiting at least 5 minutes, in order to limit hematoma and excessive blood harvesting. A 3mm incision will be made then the tissue collection will be performed using a canula, manually, by gentle aspirations into a syringe then directly transferred into a connected sterile bag. The incision will be closed with 1 stitch of 6-0 absorbable and a paraffin gauze dressing. Then, patient will be awaken and transported to the recovery room.
    Intervention Type
    Drug
    Intervention Name(s)
    Injection of the autologous adipose-derived stromal vascular fraction (AD-SVF)
    Intervention Description
    Autologous uncultured (AD-SVF) will be isolated by digestion and centrifugation of adipose tissue from lipoaspiration. Then, AD-SVF will be injected in 6 sites : 2 for the accessory labial glands (0.5mL in the upper lip and 0.5mL in the lower lip) 2 for the sublingual glands (0.5mL for each gland) 2 for the inner face of cheeks (0.5mL for each side) The volume of injection will be of 3 mL containing 30 millions of AD-SVF viable nucleated cells for the total safety dose.
    Primary Outcome Measure Information:
    Title
    Intensity of adverse reactions at the injection site at day 1
    Description
    1 day after ADSVF injection, a subjective evaluation will be done by the patient of lip sensibility, pain, oedema or ecchymosis bleeding or haematoma, bleeding or haematoma, other event through an adapted report form with phone assessment
    Time Frame
    1 day
    Title
    Intensity of adverse reactions at the injection site at day 3
    Description
    3 days after ADSVF injection, a subjective evaluation will be done by the patient of lip sensibility, pain, oedema or ecchymosis bleeding or haematoma, bleeding or haematoma, other event through an adapted report form with phone assessment.
    Time Frame
    3 days
    Title
    Intensity of adverse reactions at the injection site at day 7
    Description
    7 days after ADSVF injection, a subjective evaluation will be done by the patient of lip sensibility, pain, oedema or ecchymosis bleeding or haematoma, bleeding or haematoma, other event through an adapted report form with clinical assessment.
    Time Frame
    7 days
    Title
    Intensity of adverse reactions at the injection site at day 14
    Description
    14 days after ADSVF injection, a subjective evaluation will be done by the patient of lip sensibility, pain, oedema or ecchymosis bleeding or haematoma, bleeding or haematoma, other event through an adapted report form with clinical assessment.
    Time Frame
    14 days
    Title
    Intensity of adverse reactions at the harvesting site at day 1
    Description
    1 day after ADSVF injection, a subjective evaluation will be done by the patient of pain, oedema or ecchymosis bleeding or haematoma, inflammation or infection, other event through an adapted report form with phone assessment.
    Time Frame
    1 day
    Title
    Intensity of adverse reactions at the harvesting site at day 3
    Description
    3 days after ADSVF injection, a subjective evaluation will be done by the patient of pain, oedema or ecchymosis bleeding or haematoma, inflammation or infection, other event, through an adapted report form with phone assessment.
    Time Frame
    3 days
    Title
    Intensity of adverse reactions at the harvesting site at day 7
    Description
    7 days after ADSVF injection, a subjective evaluation will be done by the patient of pain, oedema or ecchymosis bleeding or haematoma, inflammation or infection, other event, through an adapted report form with clinical assessment.
    Time Frame
    7 days
    Title
    Intensity of adverse reactions at the harvesting site at day 14
    Description
    14 days after ADSVF injection, a subjective evaluation will be done by the patient of pain, oedema or ecchymosis bleeding or haematoma, inflammation or infection, other event through an adapted report form with clinical assessment.
    Time Frame
    14 days
    Secondary Outcome Measure Information:
    Title
    Intensity of adverse reactions at the injection site at day 15
    Description
    15 days after ADSVF injection, a subjective evaluation will be done by the patient of lip sensibility, pain, oedema or ecchymosis bleeding or haematoma, bleeding or haematoma, other event through an adapted report form with clinical assessment.
    Time Frame
    15 days
    Title
    Intensity of adverse reactions at the injection site at month 1
    Description
    1 month after ADSVF injection, a subjective evaluation will be done by the patient of lip sensibility, pain, oedema or ecchymosis bleeding or haematoma, bleeding or haematoma, other event through an adapted report form with clinical assessment.
    Time Frame
    1 month
    Title
    Intensity of adverse reactions at the injection site at month 3
    Description
    3 months after ADSVF injection, a subjective evaluation will be done by the patient of lip sensibility, pain, oedema or ecchymosis bleeding or haematoma, bleeding or haematoma, other event through an adapted report form with clinical assessment.
    Time Frame
    3 months
    Title
    Intensity of adverse reactions at the injection site at month 6
    Description
    6 months after ADSVF injection, a subjective evaluation will be done by the patient of lip sensibility, pain, oedema or ecchymosis bleeding or haematoma, bleeding or haematoma, other event through an adapted report form with clinical assessment.
    Time Frame
    6 months
    Title
    Intensity of adverse reactions at the injection site at month 7
    Description
    7 months after ADSVF injection, a subjective evaluation will be done by the patient of lip sensibility, pain, oedema or ecchymosis bleeding or haematoma, bleeding or haematoma, other event through an adapted report form with clinical assessment.
    Time Frame
    7 months
    Title
    Intensity of adverse reactions at the harvesting site at day 15
    Description
    15 days after ADSVF injection, a subjective evaluation will be done by the patient of pain, oedema or ecchymosis bleeding or haematoma, inflammation or infection, other event through an adapted report form with clinical assessment.
    Time Frame
    15 days
    Title
    Intensity of adverse reactions at the harvesting site at month 1
    Description
    1 month after ADSVF injection, a subjective evaluation will be done by the patient of pain, oedema or ecchymosis bleeding or haematoma, inflammation or infection, other event through an adapted report form with clinical assessment.
    Time Frame
    1 month
    Title
    Intensity of adverse reactions at the harvesting site at month 3
    Description
    3 months after ADSVF injection, a subjective evaluation will be done by the patient of pain, oedema or ecchymosis bleeding or haematoma, inflammation or infection, other event through an adapted report form with clinical assessment.
    Time Frame
    3 months
    Title
    Intensity of adverse reactions at the harvesting site at month 6
    Description
    6 months after ADSVF injection, a subjective evaluation will be done by the patient of pain, oedema or ecchymosis bleeding or haematoma, inflammation or infection, other event through an adapted report form with clinical assessment.
    Time Frame
    6 months
    Title
    Intensity of adverse reactions at the harvesting site at month 7
    Description
    7 months after ADSVF injection, a subjective evaluation will be done by the patient of pain, oedema or ecchymosis bleeding or haematoma, inflammation or infection, other event through an adapted report form with clinical assessment.
    Time Frame
    7 months
    Title
    primary efficiency of AD-SVF iin term of glands reparation process/repair (Minor salivary gland biopsy)
    Description
    A minor salivary gland biopsy will be done under local anaesthesia 6 months after the injection. Then, an Histological analysis (4 grades Chilson-Mason score) of minor salivary gland biopsy will be performed.
    Time Frame
    6 months
    Title
    efficacy of AD-SVF at month 1
    Description
    Salivary flow will be collected after stimulation 1 month after the injection. It is expressed in milliliter by minutes after 5 minutes of collect, and oligoptyalism isdefined by a salivary flow < 0.1 mL/mn at rest, and < 0.7 ml/mn after stimulation.
    Time Frame
    1 month
    Title
    efficacy of AD-SVF at month 3
    Description
    Salivary flow will be collected after stimulation 3 months after the injection. It is expressed in milliliter by minutes after 5 minutes of collect, and oligoptyalism isdefined by a salivary flow < 0.1 mL/mn at rest, and < 0.7 ml/mn after stimulation.
    Time Frame
    3 months
    Title
    efficacy of AD-SVF at month 6
    Description
    Salivary flow will be collected after stimulation 6 months after the injection. It is expressed in milliliter by minutes after 5 minutes of collect, and oligoptyalism isdefined by a salivary flow < 0.1 mL/mn at rest, and < 0.7 ml/mn after stimulation.
    Time Frame
    6 months
    Title
    Change in dryness of oral mucosa
    Description
    Change in dryness of oral mucosa will be assessed from Clinical Oral Dryness Score (CODS) based on 10 items realized before and, 3 and 6 months after the injection.
    Time Frame
    3 months
    Title
    Change in xerostomia Visual Analogic Scale (VAS)
    Description
    Change in VAS will be assessed from a 6-items questionnaire scored from 0 to 10 (increasing gravity) according to Likert scale.
    Time Frame
    6 months

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    65 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Patients from 18 to 65 years. Patients suffering from xerostomia and autoimmune disease including : Gougerot-Sjögren disease according to AC/EULAR criteria and Secondary Gougerot-Sjögren syndrome related to systemic diseases (sclerodermia, rheumatoid arthritis, systemic lupus erythematosus...) Xerostomia visual scale (6-item visual analogue scale questionnaire) for assessment of salivary dysfunction : score ≥ 30/60 Informed consent to participate (with signature) Negative β -HCG test and effective contraception for women being able to get pregnant Affiliation to the social security system Exclusion Criteria: Medical history of head and neck neoplasia Recent (<3 months) medication inducing and aggravating xerostomia : Standard treatment with tricyclic antidepressant and/or antipsychotics Body Mass Index < 18 Active smoking (> 5 cigarettes a day) Active infectious disease and/or active viral serologies (HIV, HCV, HBV, HTLV I/II, TPHA/VDRL) Coagulation disorders including anticoagulant and antiplatelet treatment Any temporary or definitive contraindication due to any medical or surgical unstable condition Allergy to local anesthesia and/or albumin Pregnant or breastfeeding women Adult protected by the law (tutorship and curatorship) Patients already enrolled in another study Patients under 18 years of age Person deprived of liberty Patient non-affiliated to the social security
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Laurent Guyot, Pr
    Phone
    04 91 43 63 13
    Email
    Laurent.guyot@ap-hm.fr
    First Name & Middle Initial & Last Name or Official Title & Degree
    Alexandra Giuliani
    Phone
    0491382870
    Email
    alexandra.giuliani@ap-hm.fr

    12. IPD Sharing Statement

    Plan to Share IPD
    No

    Learn more about this trial

    Safety and Potential Effect of Innovative Cell-based Therapy Using Adipose-derived Stromal Vascular Fraction in Patients With Autoimmune Xerostomia

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