Innovative Tool to Analyse Synovial Fluid of Patients With Knee Ostearthritis After IA Injection of Synvisc-one®

Overview

The objective of this trial is to assess the clinical pertinence of an innovative analytical tool (SYNODIAG) to analyze the Synovial Fluid (SF) composition and guide the patient treatment in a Proof of Concept (PoC) study using OA patients receiving IA injection of SYNVISC ONE®.

Full Title of Study: “A Proof of Concept Study in Patients Suffering of Knee Osteoarthritis (OA) and Receiving Intra-articular (IA) Injection of Synvisc-one® to Assess the Clinical Pertinence of a New Analytical Tool of Synovial Fluid”

Study Type

  • Study Type: Interventional
  • Study Design
    • Intervention Model: Single Group Assignment
    • Primary Purpose: Supportive Care
    • Masking: None (Open Label)
  • Study Primary Completion Date: October 26, 2020

Detailed Description

In a recent study on animal model (results not yet published), the use of drop deposition combined to Raman spectroscopy provided for the first time the Raman spectral signature of healthy SF. Tribological analysis of simple dried drops of SF showed the potentiality to observe physical and chemical changes due to OA process. HA concentration was correlated with the dried drop area and the increase of protein content was correlated with the height of the peripheral rim. Spectral acquisitions detailed/specified these observations as degradation of cartilage and bone tissues was measured using specific Raman band ratios. These results suggested that DDRS could be an innovative tool in OA clinical research. In this context, the Sponsor would like to assess the clinical pertinence of this innovative analytical tool in a PoC study using OA patients receiving IA injection of SYNVISC ONE®.

Interventions

  • Device: Synvisc-One
    • SYNVISC-ONE® (Hylan G-F 20), 10 mL single-injection viscosupplement Status : CE marked (CE 0086) class III Medical Device The IP is used according to its usual dosage, administration and indication

Arms, Groups and Cohorts

  • Other: Injection of SYNVISC-ONE
    • Patients suffering from symptomatic knee osteoarthritis (OA), receiving intra-articular (IA) injection of SYNVISC-ONE® (Hylan G-F 20; 10 mL single-injection viscosupplement)

Clinical Trial Outcome Measures

Primary Measures

  • Detection of variation of the composition of Synovial Fluid after hyaluronic acid viscosupplementation in Osteoarthritis patients receiving SYNVISC-ONE® injection
    • Time Frame: 6 months (between T0 and T6 visit)
    • Tribological properties (i.e. the dried drop surface and the peripheral height profile) of the synovial fluid will be analyzed through optical microscopy (2D morphological examinations) in OA patients receiving SYNVISC-ONE® injection

Secondary Measures

  • Detection of Synovial fluid tribological properties through interferometry
    • Time Frame: 6 months (between T0 and T6 visit)
    • Topography measurement (3D tribological examination) will be performed using white light interferometry (smartWLI-microscope, GBS mbH, Germany) on the periphery of the drops.
  • Detection of Synovial fluid molecular structural and chemical changes using a Raman confocal microscope
    • Time Frame: 6 months (between T0 and T6 visit)
    • Based on Raman spectroscopy
  • Detection of dried drops physicochemical index
    • Time Frame: 6 months (between T0 and T6 visit)
    • Based on surface of dried drops and Raman ratios
  • Variation of Visual Analogue Scale for the mean knee pain at rest and while walking over the last month
    • Time Frame: 6 months (between T0 and T6 visit)
    • The pain Visual Analogue scale (VAS) is a continuous scale comprised of a horizontal line, usually 10 centimeters in length, anchored by 2 verbal descriptors, one for each symptom extreme.
  • Variation of Knee injury and Osteoarthritis Outcome Score using a self-administered questionnaire
    • Time Frame: 6 months (between T0 and T6 visit)
    • The KOOS outcome score is a 42-item self-administrated questionnaire comprising 5 subscales: Pain, Symptoms, Activities of Daily Living, Sports and Recreation function, and Quality Of Life. A separate score ranging from 0 to 100, where 100 represents the best result, will be calculated for each subscale. A global score will be calculated by summing the score of each subscale.
  • Variation of Visual Analogue Scale for patient global assessment of disease activity
    • Time Frame: 6 months (between T0 and T6 visit)
    • The Visual Analogue Scale (VAS) is a continuous scale comprised of a horizontal line, usually 10 centimeters in length, anchored by one verbal descriptors for Global Assessment of disease activity.
  • Determination of Semi-quantitative Whole ORgan Magnetic Imaging Score score of the joint
    • Time Frame: At baseline visit (T0)
    • MRI Imaging will be analyzed for WORMS by central reading in order to find correlation between the Imaging and the synovial fluid composition.
  • Responder rate to treatment defined as changes in knee pain and/or knee function and/or patients disease activity according to OMERACT OARSI criteria
    • Time Frame: 6 months (between T0 and T6 visit)
    • Responder criteria for osteoarthritis clinical trials will be based on the questionnaires describe above.
  • Tolerance to the product
    • Time Frame: 6 months (between T0 and T6 visit)
    • Number of Adverse events (AE or Adverse Device Effect or Device Deficiency; will be coded in terms of SOC and LLT using the last version of MedDRA) and drop offs

Participating in This Clinical Trial

Inclusion Criteria

  • Male or female ≥ 40 years of age with BMI ≤ 35 kg/m2
  • Femorotibial knee OA (Uni- or bilateral):
  • Responding to clinical and radiological criteria of American College of Rheumatology (ACR)
  • Symptomatic for more than 6 months in the most painful knee
  • Moderate-to-severe knee pain: knee pain score evaluated on VAS (0-100) ≥ 40 over the last month at the inclusion visit (the most painful knee is considered)
  • Eligible for knee viscosupplementation using SYNVISC-ONE®
  • Knee swelling justifying SF aspiration at baseline – Able to follow the instructions of the study
  • Having signed an informed consent

Exclusion Criteria

1. Related to the OA pathology:

  • Recent trauma (< 6 months) of the knee responsible of the symptomatic knee Concurrent articular disease interfering with the evaluation of OA and/or pain such as but not limited to articular dysplasia, aseptic osteonecrosis, acromegaly, Paget's disease, hemophilia, hemochromatosis, chondromatosis, villonodular synovitis of the knee, seronegative spondyloarthropathy, rheumatoid arthritis, gouty arthritis, infectious arthritis, radiculalgia in the lower limbs, arteritis, chondrocalcinosis x-rays diagnosed and Calcium PyroPhosphate Dihydrate crystal deposition disease (CPPD)
  • Hemarthrosis
  • Prosthesis in the target knee

2. Related to treatment:

  • Analgesics to manage knee pain 24h before inclusion visit
  • Corticosteroids injection in the target knee in the last 3 months before injection (excepted for low dose injection following SF aspiration at V1 as recommended by standard treatment guidelines)
  • Hyaluronan injection in the target knee in the last 6 months before injection
  • Arthroscopy in the last 3 months before injection
  • Oral corticotherapy ≥ 5mg/day (in Prednisolone equivalent) in the last 3 months before injection
  • Change in the dosage regimen of symptomatic slow-acting drugs for osteoarthritis (SYSADOA) or dietary supplement, i.e., curcuma extract, chondroitin, glucosamine, diacerein or avocado-soya unsaponifiables in the last 3 months before injection
  • An anticipated need for any forbidden OA treatments during the trial
  • Contraindications to SYNVISC-ONE®: hypersensitivity or allergy to the product components and infections or skin diseases in the area of the injection site
  • Anticoagulant (such as coumarinic) and heparin before injection

3. Related to associated diseases:

  • Severe and uncontrolled diseases (type I diabetes, liver failure, renal failure, lung/heart disease, progressive malignant neoplasia or in remission for less than 5 years, HIV
  • Malignancy or history of malignancy, or other major disease (e.g., systemic fungal infection) or other severe uncontrolled conditions (e.g., drug or alcohol abuse), that are significant and/or that may pose a health risk to the subject in the study or may have an impact on the study assessments
  • High risk of hemorrhage and risk of infection at the site of injection
  • Anticipated need for any surgical or other invasive procedure during the trial including prosthesis in the target knee

4. Related to patients:

  • Close collaborators to the Sponsor, the study coordinator or the Investigator
  • Participation in a clinical trial in the last 3 months before injection
  • Patient under guardianship or judicial protection
  • Pregnancy, breastfeeding, planned conception, or premenopausal women without effective contraception (pill, patch, ring, diaphragm, implant and intrauterine device), tubal ligation or hysterectomy

5. Related to MRI counter-indication:

  • Risk groups for MRI scanning due to magnetic field: metal in body: pacemaker/AICD/ICD (coronary defibrillator), nervus vagus stimulator, artificial heart valve (depending on type), metal clips on cerebral arteries or veins, metal particles in eye, port-a-cath, metal stents, hydrocephalic pump/insuline pump, metal implants; f/e screws, prostheses, piercings
  • Claustrophobia or serious mobility problem (uncontrolled Parkinson, tremors)

Gender Eligibility: All

Minimum Age: 40 Years

Maximum Age: 80 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Pulsalys
  • Collaborator
    • Artialis
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Charles CHAPELLE, MD, Principal Investigator, Centre Medical Chant d’Oiseau
  • Overall Contact(s)
    • Bérénice Costes, PhD, 003242427706, berenice.costes@artialis.com

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