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出境医 / 临床实验 / RElevance of UltraSonography for Assessing Salivary Gland Involvement in Systemic Sclerosis (SSc) (REUSSI-SSc)

RElevance of UltraSonography for Assessing Salivary Gland Involvement in Systemic Sclerosis (SSc) (REUSSI-SSc)

Study Description
Brief Summary:
As fibrosis of salivary glands is supposed to be the main mechanism involved in Systemic sclerosis (SSc)-associated sicca syndrome, Ultrasonography , biopsy and measuring gland elasticity (by ARFI (Acoustic Radiation Force Impulse)) in SSc patients could also constitute a relevant method to assess the potential alterations of echostructure of major salivary glands and the fibrosis of Salivary Glands in this disease.

Condition or disease Intervention/treatment Phase
Systemic Sclerosis Diagnostic Test: Minor Salivary gland Biopsy Diagnostic Test: ARFI Diagnostic Test: MSG US Not Applicable

Detailed Description:
Systemic sclerosis (SSc) is a rare autoimmune chronic disorder characterised by vascular hyper-reactivity and fibrosis of the skin as well as internal organs. Intimal hyperplasia, endothelial dysfunction and occlusive vasculopathy are the underlying basis of these chronic vascular damages. The expression of the vasculopathy especially includes Raynaud phenomenon (RP), digital ulcers (DUs), gastro-intestinal involvement and pulmonary arterial hypertension (PAH). Sicca syndrome is clinically characterised by dryness of the eyes (xerophthalmia) and mouth (xerostomia). The prevalence of sicca symptoms is up to 70% in prospective series of SSc patients. Sicca syndrome is supposed to be primarily related to glandular fibrosis. The prevalence of primary Sjögren Syndrome (pSS) among SSc patients, as defined by the American-European Consensus Group criteria is around 15%. Sicca syndrome is therefore a frequent feature in SSc and constitutes an important cause of quality of life's impairment in SSc If studies have already evaluated clinical and histological alterations of minor salivary glands secondary to sicca syndrome in SSc , only few studies used the recent ACR(American College of Rheumatology) 2013 classification criteria for SSc to select patients. SGUS(Salivary Gland UltraSonography) evaluation in SSc has never been assessed to date. Potential alterations of MSG (Major Salivary Gland) echostructure in SSc have never been described to date. The performances and reliability of SGUS to assessed MSG involvement in SSc are still to be determined. As fibrosis of salivary glands is supposed to be the main mechanism involved in SSc-associated sicca syndrome, measuring salivary-gland elasticity using ARFI-ultrasonography in SSc patients could also constitute a relevant method to assess the fibrosis of MSG in this disease. A cross-sectional pilot study is therefore needed to explore these relevant questions about sicca syndrome in SSc.
Study Design
Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 75 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: cross-sectionnal pilot study
Masking: Single (Outcomes Assessor)
Masking Description: The examiner performin the evaluation of ultrasound features of the main salivary glands will not have acess at the first part of patient evaluation.
Primary Purpose: Diagnostic
Official Title: RElevance of UltraSonography for Assessing Salivary Gland Involvement in Systemic Sclerosis (SSc)
Actual Study Start Date : December 2, 2019
Actual Primary Completion Date : December 2, 2019
Estimated Study Completion Date : December 30, 2022
Arms and Interventions
Arm Intervention/treatment
Experimental: Patients reporting subjective sicca symptoms
HAQ(Health Assessment Questionnaire) Score, bilateral schirmer 's test, unstimulated whole salivary flow rate, blood sample for immunologic evaluation
 Diagnostic Test: Minor Salivary gland Biopsy
Minor salivary gland biopsy with injection of lidocain

Diagnostic Test: ARFI
Acoustic Radiation Force Impulse on Major Salivary Glands

Diagnostic Test: MSG US
Ultrasonography of Major Salivary Glands
Experimental: Patients without subjective sicca symptoms
HAQ(Health Assessment Questionnaire) score, bilateral schirmer 's test, unstimulated whole salivary flow rate, blood sample for immunologic evaluation
 Diagnostic Test: ARFI
Acoustic Radiation Force Impulse on Major Salivary Glands

Diagnostic Test: MSG US
Ultrasonography of Major Salivary Glands
Outcome Measures
Primary Outcome Measures :
  1. Ultrasonography characteristics of major salivary glands [ Time Frame: up to six months (at evaluation visit) ]

    Ultrasonography characteristics of major salivary glands based on Salaffi's composite score.

    each MSG will be scored as followed:

    • grade 0 = normal homogeneous glands;
    • grade 1 = Homogenous borders, slightly heterogeneous parenchyma,
    • grade 2 = Homogenous borders, multiple hypoechogenic areas measuring < 2 mm,
    • grade 3 = multiple hypoechogenic areas measuring 2-6 mm or irregular borders or invisible posterior part of the gland;
    • grade 4 = unstructured glandular parenchyma with multiple hypoechogenic areas measuring >6 mm or calcifications with echogenic bands.

    In each patient, 4 grades can be obtained (1 grade per gland);

    the sum of these 4 grades (range 0-16) will be the Salaffi's score.

    A score of 0 has the best outcome, of 16 the worse


  2. Ultrasonography characteristics of major salivary glands [ Time Frame: up to six months (at evaluation visit) ]
    Ultrasonography characteristics of major salivary glands based on bilateral ARFI(Acoustic radiation force Impulse) elastometry


Secondary Outcome Measures :
  1. Variants of the Salaffi score [ Time Frame: up to six months (evaluation visit) ]

    Scores of Hocevar,based on the same ultrasound parameters but with a weighting different from that of Salaffi in the calculation of the score.

    Echostructure of the four salivary glands will be graded 0 to 12 ; the sum of these 4 grades (range 0-48) will be the Hocevar's score. A score of 0 has the best outcome, of 48 the worse.


  2. Variants of the Salaffi score [ Time Frame: up to six months (evaluation visit) ]

    Scores of Milic,based on the same ultrasound parameters but with a weighting different from that of Salaffi in the calculation of the score.

    Echostructure of the four salivary glands will be graded 0 to 3 ; the sum of these 4 grades (range 0-12) will be the Milic's score. A score of 0 has the best outcome, of 12 the worse.


  3. Variants of the Salaffi score [ Time Frame: up to six months (evaluation visit) ]

    Scores Jousse-Joulin / Cornec constituting , based on the same ultrasound parameters but with a weighting different from that of Salaffi in the calculation of the score.

    Echostructure of the four salivary glands will be graded 0 to 4 ; the sum of these 4 grades (range 0-16) will be the Jousse-Joulin/Cornec's score.

    A score of 0 has the best outcome, of 16 the worse.


  4. Biopsy of the minor salivary glands [ Time Frame: up to six months (evaluation visit) ]

    Biopsies of the minor salivary glands with standardized histological characterization of the Chisholm score.

    Chisholm'score will evaluate the number of lymphocytic foci/4mm2 grade 1 : none or slight, grade 2 : less than 50 lymphocytes and histocytes, grade 3 : one focus with at least 50 lymphocytes, grade 4 : More than one focus with at least 50 lymphocytes,

    Grade 1 has the best outcome, grade 4 the worse.


  5. Biopsy of the minor salivary glands [ Time Frame: up to six months (evaluation visit) ]

    Biopsies of the minor salivary glands with standardized characterization of the focus score.

    Focus score : the number of mononuclear cell infiltrates containing at least 50 inflammatory cells in a 4 mm2 glandular section,

    Focus score 0 = no mononuclear cell infiltrate containing at least 50 inflammatory cells in a 4 mm2 glandular section,

    Focus score =1 or >1 : one or more mononuclear cell infiltrates containing at least 50 inflammatory cells in a 4 mm2 glandular section,

    Focus score 0 has the best outcome Focus score =1 or >1 has the worse outcome


  6. Biopsy of the minor salivary glands [ Time Frame: up to six months (evaluation visit) ]
    Biopsies of the minor salivary glands with evaluation of fibrosis assessed from F1 to F4

  7. Evaluation of the presence or absence of objective criteria of Sjogren [ Time Frame: up to six months (evaluation visit) ]
    Evaluation of the presence or absence of objective criteria of Sjogren according to salivary flow test

  8. Evaluation of the presence or absence of objective criteria of Sjogren [ Time Frame: up to six months (evaluation visit) ]
    Evaluation of the presence or absence of objective criteria of Sjogren according to Schirmer test.

  9. Clinical evaluation of systemic scleroderma lesions [ Time Frame: up to six months (evaluation visit) ]
    forms of the disease

  10. Clinical evaluation of systemic scleroderma lesions [ Time Frame: up to six months (evaluation visit) ]
    duration of evolution of the disease

  11. Clinical evaluation of systemic scleroderma lesions [ Time Frame: up to six months (evaluation visit) ]
    visceral damage : Presence or absence of pulmonary involvement on CT scan, Presence or absence of pulmonary arterial hypertension on echocardiography.

  12. Clinical evaluation of systemic scleroderma lesions [ Time Frame: up to six months (evaluation visit) ]

    immunological data : Positivity of : Anti SSA(Anti Sjögren Syndrom A) antibodies,Anti SSb(Anti Sjögren syndrom B) antibodies,Anti Topoisomerase antibodies, Anti Centromere antibodies, Anti RNA polymerase III antibodies

    Using Indirect ImmunoFluorescence (IFI) ( as binary parameter (positive or negative)



Eligibility Criteria
Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients over eighteen years old;
  • Fulfilling 2013 ACR classification criteria for Systemic sclerosis (Van den Hoogen et al. 2013);
  • 60 patients with subjective sicca symptoms reported by a standardised questionnaire (Vitali C et al. 2002);
  • 15 patients without sicca symptoms;
  • Who has signed an informed consent
  • Benefiting from a social security scheme

Exclusion Criteria:

  • Treatment: current (or in the past 6 months) immunosuppressive treatment by rituximab or cyclophosphamide (representing less than 5% of SSc patients in the investigator's centres);
  • Current (or in the past 6 months) treatment with drugs with anti-cholinergic properties (Selective Serotonin Reuptake Inhibitors and anti-histaminic inhibitors (hydroxyzine));
  • Current treatment with antiplatelet aggregates
  • Anti-vitamin K treatment (increasing risk of bleeding during minor salivary gland biopsy); and oral anti-coagulant
  • Known abnormal coagulation (prolonged aPPT(activated partial thromboplastin time) and / or PT (Prothrombin time ( <70%)), or known thrombocytopenia (<150,000 platelets / mm3)
  • Known secondary sicca symptoms : history of head-and-neck radiotherapy, hepatitis C infection, AIDS, sarcoidosis, amyloidosis, graft-vs-host disease and IgG4(Isotype's immunoGlobulin G4)-related disease;
  • Pregnancy or breastfeeding mothers;
  • Known intolerance/allergy to xylocain injection;
  • Adults legally protected (under judicial protection, guardianship, or supervision), inability to consent.
Contacts and Locations

Contacts
Layout table for location contacts
Contact: Patrick JEGO, MD 02 99 26 71 28 patrick.jego@chu-rennes.fr
Contact: Alain Lescoat 02 99 26 71 28 alain.lescoat@chu-rennes.fr

Locations
Layout table for location information
France
CHU Brest Service de Rhumatologie Recruiting
Brest, France, 29000
Contact: Sandrine Jousse-Joulin, MD       sandrine.joulin@chu-brest.fr   
CHU rennes Recruiting
Rennes, France, 35000
Contact: Alain Lescoat, MD       alain.lescoat@chu-rennes.fr   
Contact: Patrick JEGO, MD       patrick.jego@chu-rennes.fr   
CHU Tours, Service de médecine interne Recruiting
Tours, France, 37000
Contact: Elisabeth DIOT, MD       elisabeth.diot@chu-tours.fr   
Sponsors and Collaborators
Rennes University Hospital
Investigators
Layout table for investigator information
Principal Investigator: Patrick JEGO, MD University Hospital of Rennes
Tracking Information
First Submitted Date  ICMJE April 1, 2019
First Posted Date  ICMJE June 28, 2019
Last Update Posted Date April 15, 2021
Actual Study Start Date  ICMJE December 2, 2019
Actual Primary Completion Date December 2, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 1, 2019)
  • Ultrasonography characteristics of major salivary glands [ Time Frame: up to six months (at evaluation visit) ]
    Ultrasonography characteristics of major salivary glands based on Salaffi's composite score. each MSG will be scored as followed:
    • grade 0 = normal homogeneous glands;
    • grade 1 = Homogenous borders, slightly heterogeneous parenchyma,
    • grade 2 = Homogenous borders, multiple hypoechogenic areas measuring < 2 mm,
    • grade 3 = multiple hypoechogenic areas measuring 2-6 mm or irregular borders or invisible posterior part of the gland;
    • grade 4 = unstructured glandular parenchyma with multiple hypoechogenic areas measuring >6 mm or calcifications with echogenic bands.
    In each patient, 4 grades can be obtained (1 grade per gland); the sum of these 4 grades (range 0-16) will be the Salaffi's score. A score of 0 has the best outcome, of 16 the worse
  • Ultrasonography characteristics of major salivary glands [ Time Frame: up to six months (at evaluation visit) ]
    Ultrasonography characteristics of major salivary glands based on bilateral ARFI(Acoustic radiation force Impulse) elastometry
Original Primary Outcome Measures  ICMJE
 (submitted: June 25, 2019)
  • Ultrasonography characteristics of major salivary glands [ Time Frame: up to six months (at evaluation visit) ]
    Ultrasonography characteristics of major salivary glands based on Salaffi's composite score. each MSG will be scored as followed:
    • grade 0 = normal homogeneous glands;
    • grade 1 = Homogenous borders, slightly heterogeneous parenchyma,
    • grade 2 = Homogenous borders, multiple hypoechogenic areas measuring < 2 mm,
    • grade 3 = multiple hypoechogenic areas measuring 2-6 mm or irregular borders or invisible posterior part of the gland;
    • grade 4 = destructured glandular parenchylma with multiple hypoechogenic areas measuring >6 mm or calcifications with echogenic bands.
    In each patient, 4 grades can be obtained (1 grade per gland); the sum of these 4 grades (range 0-16) will be the Salaffi's score. A score of 0 has the best outcome, of 16 the worse
  • Ultrasonography characteristics of major salivary glands [ Time Frame: up to six months (at evaluation visit) ]
    Ultrasonography characteristics of major salivary glands based on bilateral ARFI elastometry
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 1, 2019)
  • Variants of the Salaffi score [ Time Frame: up to six months (evaluation visit) ]
    Scores of Hocevar,based on the same ultrasound parameters but with a weighting different from that of Salaffi in the calculation of the score. Echostructure of the four salivary glands will be graded 0 to 12 ; the sum of these 4 grades (range 0-48) will be the Hocevar's score. A score of 0 has the best outcome, of 48 the worse.
  • Variants of the Salaffi score [ Time Frame: up to six months (evaluation visit) ]
    Scores of Milic,based on the same ultrasound parameters but with a weighting different from that of Salaffi in the calculation of the score. Echostructure of the four salivary glands will be graded 0 to 3 ; the sum of these 4 grades (range 0-12) will be the Milic's score. A score of 0 has the best outcome, of 12 the worse.
  • Variants of the Salaffi score [ Time Frame: up to six months (evaluation visit) ]
    Scores Jousse-Joulin / Cornec constituting , based on the same ultrasound parameters but with a weighting different from that of Salaffi in the calculation of the score. Echostructure of the four salivary glands will be graded 0 to 4 ; the sum of these 4 grades (range 0-16) will be the Jousse-Joulin/Cornec's score. A score of 0 has the best outcome, of 16 the worse.
  • Biopsy of the minor salivary glands [ Time Frame: up to six months (evaluation visit) ]
    Biopsies of the minor salivary glands with standardized histological characterization of the Chisholm score. Chisholm'score will evaluate the number of lymphocytic foci/4mm2 grade 1 : none or slight, grade 2 : less than 50 lymphocytes and histocytes, grade 3 : one focus with at least 50 lymphocytes, grade 4 : More than one focus with at least 50 lymphocytes, Grade 1 has the best outcome, grade 4 the worse.
  • Biopsy of the minor salivary glands [ Time Frame: up to six months (evaluation visit) ]
    Biopsies of the minor salivary glands with standardized characterization of the focus score. Focus score : the number of mononuclear cell infiltrates containing at least 50 inflammatory cells in a 4 mm2 glandular section, Focus score 0 = no mononuclear cell infiltrate containing at least 50 inflammatory cells in a 4 mm2 glandular section, Focus score =1 or >1 : one or more mononuclear cell infiltrates containing at least 50 inflammatory cells in a 4 mm2 glandular section, Focus score 0 has the best outcome Focus score =1 or >1 has the worse outcome
  • Biopsy of the minor salivary glands [ Time Frame: up to six months (evaluation visit) ]
    Biopsies of the minor salivary glands with evaluation of fibrosis assessed from F1 to F4
  • Evaluation of the presence or absence of objective criteria of Sjogren [ Time Frame: up to six months (evaluation visit) ]
    Evaluation of the presence or absence of objective criteria of Sjogren according to salivary flow test
  • Evaluation of the presence or absence of objective criteria of Sjogren [ Time Frame: up to six months (evaluation visit) ]
    Evaluation of the presence or absence of objective criteria of Sjogren according to Schirmer test.
  • Clinical evaluation of systemic scleroderma lesions [ Time Frame: up to six months (evaluation visit) ]
    forms of the disease
  • Clinical evaluation of systemic scleroderma lesions [ Time Frame: up to six months (evaluation visit) ]
    duration of evolution of the disease
  • Clinical evaluation of systemic scleroderma lesions [ Time Frame: up to six months (evaluation visit) ]
    visceral damage : Presence or absence of pulmonary involvement on CT scan, Presence or absence of pulmonary arterial hypertension on echocardiography.
  • Clinical evaluation of systemic scleroderma lesions [ Time Frame: up to six months (evaluation visit) ]
    immunological data : Positivity of : Anti SSA(Anti Sjögren Syndrom A) antibodies,Anti SSb(Anti Sjögren syndrom B) antibodies,Anti Topoisomerase antibodies, Anti Centromere antibodies, Anti RNA polymerase III antibodies Using Indirect ImmunoFluorescence (IFI) ( as binary parameter (positive or negative)
Original Secondary Outcome Measures  ICMJE
 (submitted: June 25, 2019)
  • Variants of the Salaffi score [ Time Frame: up to six months (evaluation visit) ]
    Scores of Hocevar,based on the same ultrasound parameters but with a weighting different from that of Salaffi in the calculation of the score. Echostructure of the four salivary glands will be graded 0 to 12 ; the sum of these 4 grades (range 0-48) will be the Hocevar's score. A score of 0 has the best outcome, of 48 the worse.
  • Variants of the Salaffi score [ Time Frame: up to six months (evaluation visit) ]
    Scores of Milic,based on the same ultrasound parameters but with a weighting different from that of Salaffi in the calculation of the score. Echostructure of the four salivary glands will be graded 0 to 3 ; the sum of these 4 grades (range 0-12) will be the Milic's score. A score of 0 has the best outcome, of 12 the worse.
  • Variants of the Salaffi score [ Time Frame: up to six months (evaluation visit) ]
    Scores Jousse-Joulin / Cornec constituting , based on the same ultrasound parameters but with a weighting different from that of Salaffi in the calculation of the score. Echostructure of the four salivary glands will be graded 0 to 4 ; the sum of these 4 grades (range 0-16) will be the Jousse-Joulin/Cornec's score. A score of 0 has the best outcome, of 16 the worse.
  • Biopsy of the minor salivary glands [ Time Frame: up to six months (evaluation visit) ]
    Biopsies of the minor salivary glands with standardized histological characterization of the Chisholm score. Chisholm'score will evaluate the number of lymphocityc foci/4mm2 grade 1 : none or slight, grade 2 : less than 50 lymphoctyes and histocytes, grade 3 : one focus with at least 50 lymphocytes, grade 4 : More than one focus with at least 50 lymphocytes, Grade 1 has the best outcome, grade 4 the worse.
  • Biopsy of the minor salivary glands [ Time Frame: up to six months (evaluation visit) ]
    Biopsies of the minor salivary glands with standardized characterization of the focus score. Focus score : the number of mononuclear cell infiltrates containing at least 50 inflammatory cells in a 4 mm2 glandular section, Focus score 0 = no mononuclear cell infiltrate containing at least 50 inflammatory cells in a 4 mm2 glandular section, Focus score =1 or >1 : one or more mononuclear cell infiltrates containing at least 50 inflammatory cells in a 4 mm2 glandular section, Focus score 0 has the best outcome Focus score =1 or >1 has the worse outcome
  • Biopsy of the minor salivary glands [ Time Frame: up to six months (evaluation visit) ]
    Biopsies of the minor salivary glands with evaluation of fibrosis assessed from F1 to F4
  • Evaluation of the presence or absence of objective criteria of Sjogren [ Time Frame: up to six months (evaluation visit) ]
    Evaluation of the presence or absence of objective criteria of Sjogren according to salivary flow test
  • Evaluation of the presence or absence of objective criteria of Sjogren [ Time Frame: up to six months (evaluation visit) ]
    Evaluation of the presence or absence of objective criteria of Sjogren according to Schirmer test.
  • Clinical evaluation of systemic scleroderma lesions [ Time Frame: up to six months (evaluation visit) ]
    forms of the disease
  • Clinical evaluation of systemic scleroderma lesions [ Time Frame: up to six months (evaluation visit) ]
    duration of evolution of the disease
  • Clinical evaluation of systemic scleroderma lesions [ Time Frame: up to six months (evaluation visit) ]
    visceral damage : Presence or absence of pulmonary invovlement on CT scan, Presence or absence of pulmonary arterial hypertension on echocardiography.
  • Clinical evaluation of systemic scleroderma lesions [ Time Frame: up to six months (evaluation visit) ]
    immunological data : Positivity of : Anti SSA antibodies,Anti SSb antibodies,Anti Topoismerase antibodies, Anti Centromère antibodies, Anti RNA polymerase III antibodies Using IFI as binary parameter (positive or negative)
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE RElevance of UltraSonography for Assessing Salivary Gland Involvement in Systemic Sclerosis (SSc)
Official Title  ICMJE RElevance of UltraSonography for Assessing Salivary Gland Involvement in Systemic Sclerosis (SSc)
Brief Summary As fibrosis of salivary glands is supposed to be the main mechanism involved in Systemic sclerosis (SSc)-associated sicca syndrome, Ultrasonography , biopsy and measuring gland elasticity (by ARFI (Acoustic Radiation Force Impulse)) in SSc patients could also constitute a relevant method to assess the potential alterations of echostructure of major salivary glands and the fibrosis of Salivary Glands in this disease.
Detailed Description Systemic sclerosis (SSc) is a rare autoimmune chronic disorder characterised by vascular hyper-reactivity and fibrosis of the skin as well as internal organs. Intimal hyperplasia, endothelial dysfunction and occlusive vasculopathy are the underlying basis of these chronic vascular damages. The expression of the vasculopathy especially includes Raynaud phenomenon (RP), digital ulcers (DUs), gastro-intestinal involvement and pulmonary arterial hypertension (PAH). Sicca syndrome is clinically characterised by dryness of the eyes (xerophthalmia) and mouth (xerostomia). The prevalence of sicca symptoms is up to 70% in prospective series of SSc patients. Sicca syndrome is supposed to be primarily related to glandular fibrosis. The prevalence of primary Sjögren Syndrome (pSS) among SSc patients, as defined by the American-European Consensus Group criteria is around 15%. Sicca syndrome is therefore a frequent feature in SSc and constitutes an important cause of quality of life's impairment in SSc If studies have already evaluated clinical and histological alterations of minor salivary glands secondary to sicca syndrome in SSc , only few studies used the recent ACR(American College of Rheumatology) 2013 classification criteria for SSc to select patients. SGUS(Salivary Gland UltraSonography) evaluation in SSc has never been assessed to date. Potential alterations of MSG (Major Salivary Gland) echostructure in SSc have never been described to date. The performances and reliability of SGUS to assessed MSG involvement in SSc are still to be determined. As fibrosis of salivary glands is supposed to be the main mechanism involved in SSc-associated sicca syndrome, measuring salivary-gland elasticity using ARFI-ultrasonography in SSc patients could also constitute a relevant method to assess the fibrosis of MSG in this disease. A cross-sectional pilot study is therefore needed to explore these relevant questions about sicca syndrome in SSc.
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
cross-sectionnal pilot study
Masking: Single (Outcomes Assessor)
Masking Description:
The examiner performin the evaluation of ultrasound features of the main salivary glands will not have acess at the first part of patient evaluation.
Primary Purpose: Diagnostic
Condition  ICMJE Systemic Sclerosis
Intervention  ICMJE
  • Diagnostic Test: Minor Salivary gland Biopsy
    Minor salivary gland biopsy with injection of lidocain
  • Diagnostic Test: ARFI
    Acoustic Radiation Force Impulse on Major Salivary Glands
  • Diagnostic Test: MSG US
    Ultrasonography of Major Salivary Glands
Study Arms  ICMJE
  • Experimental: Patients reporting subjective sicca symptoms
    HAQ(Health Assessment Questionnaire) Score, bilateral schirmer 's test, unstimulated whole salivary flow rate, blood sample for immunologic evaluation
    Interventions:
    • Diagnostic Test: Minor Salivary gland Biopsy
    • Diagnostic Test: ARFI
    • Diagnostic Test: MSG US
  • Experimental: Patients without subjective sicca symptoms
    HAQ(Health Assessment Questionnaire) score, bilateral schirmer 's test, unstimulated whole salivary flow rate, blood sample for immunologic evaluation
    Interventions:
    • Diagnostic Test: ARFI
    • Diagnostic Test: MSG US
Publications *
  • Salaffi F, Argalia G, Carotti M, Giannini FB, Palombi C. Salivary gland ultrasonography in the evaluation of primary Sjögren's syndrome. Comparison with minor salivary gland biopsy. J Rheumatol. 2000 May;27(5):1229-36.
  • Hocevar A, Ambrozic A, Rozman B, Kveder T, Tomsic M. Ultrasonographic changes of major salivary glands in primary Sjogren's syndrome. Diagnostic value of a novel scoring system. Rheumatology (Oxford). 2005 Jun;44(6):768-72. Epub 2005 Mar 1.
  • Milic VD, Petrovic RR, Boricic IV, Radunovic GL, Pejnovic NN, Soldatovic I, Damjanov NS. Major salivary gland sonography in Sjögren's syndrome: diagnostic value of a novel ultrasonography score (0-12) for parenchymal inhomogeneity. Scand J Rheumatol. 2010 Mar;39(2):160-6. doi: 10.3109/03009740903270623.
  • Jousse-Joulin S, Milic V, Jonsson MV, Plagou A, Theander E, Luciano N, Rachele P, Baldini C, Bootsma H, Vissink A, Hocevar A, De Vita S, Tzioufas AG, Alavi Z, Bowman SJ, Devauchelle-Pensec V; US-pSS Study Group. Is salivary gland ultrasonography a useful tool in Sjögren's syndrome? A systematic review. Rheumatology (Oxford). 2016 May;55(5):789-800. doi: 10.1093/rheumatology/kev385. Epub 2015 Dec 14. Review.
  • Cornec D, Jousse-Joulin S, Pers JO, Marhadour T, Cochener B, Boisramé-Gastrin S, Nowak E, Youinou P, Saraux A, Devauchelle-Pensec V. Contribution of salivary gland ultrasonography to the diagnosis of Sjögren's syndrome: toward new diagnostic criteria? Arthritis Rheum. 2013 Jan;65(1):216-25. doi: 10.1002/art.37698.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 25, 2019) 		75
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 30, 2022
Actual Primary Completion Date December 2, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Patients over eighteen years old;
  • Fulfilling 2013 ACR classification criteria for Systemic sclerosis (Van den Hoogen et al. 2013);
  • 60 patients with subjective sicca symptoms reported by a standardised questionnaire (Vitali C et al. 2002);
  • 15 patients without sicca symptoms;
  • Who has signed an informed consent
  • Benefiting from a social security scheme

Exclusion Criteria:

  • Treatment: current (or in the past 6 months) immunosuppressive treatment by rituximab or cyclophosphamide (representing less than 5% of SSc patients in the investigator's centres);
  • Current (or in the past 6 months) treatment with drugs with anti-cholinergic properties (Selective Serotonin Reuptake Inhibitors and anti-histaminic inhibitors (hydroxyzine));
  • Current treatment with antiplatelet aggregates
  • Anti-vitamin K treatment (increasing risk of bleeding during minor salivary gland biopsy); and oral anti-coagulant
  • Known abnormal coagulation (prolonged aPPT(activated partial thromboplastin time) and / or PT (Prothrombin time ( <70%)), or known thrombocytopenia (<150,000 platelets / mm3)
  • Known secondary sicca symptoms : history of head-and-neck radiotherapy, hepatitis C infection, AIDS, sarcoidosis, amyloidosis, graft-vs-host disease and IgG4(Isotype's immunoGlobulin G4)-related disease;
  • Pregnancy or breastfeeding mothers;
  • Known intolerance/allergy to xylocain injection;
  • Adults legally protected (under judicial protection, guardianship, or supervision), inability to consent.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Patrick JEGO, MD 02 99 26 71 28 patrick.jego@chu-rennes.fr
Contact: Alain Lescoat 02 99 26 71 28 alain.lescoat@chu-rennes.fr
Listed Location Countries  ICMJE France
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04001556
Other Study ID Numbers  ICMJE 35RC18_9905
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Rennes University Hospital
Study Sponsor  ICMJE Rennes University Hospital
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Patrick JEGO, MD University Hospital of Rennes
PRS Account Rennes University Hospital
Verification Date April 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

治疗医院

新药特效药

前沿医讯