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

Primary Purpose

Knee Osteoarthritis, Intra-Articular Injection

Status
Completed
Phase
Not Applicable
Locations
Belgium
Study Type
Interventional
Intervention
Synvisc-One
Sponsored by
Pulsalys
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional supportive care trial for Knee Osteoarthritis focused on measuring Osteoarthritis, food supplement, SYNVISC, Synovial Fluid analysis

Eligibility Criteria

40 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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 macro-trauma (< 6 months) of the knee responsible of the symptomatic knee. Micro-trauma are allowed according the Investigator's discretion
    • 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

    • 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 anti-vitamin K (such as coumarinic) 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)

Sites / Locations

  • Centre Medical Chant d'Oiseau
  • Hopital Delta, CHIREC
  • Cliniques Universitaires Saint Luc - UCL

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

Injection of SYNVISC-ONE

Arm Description

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

Outcomes

Primary Outcome Measures

Detection of variation of the composition of Synovial Fluid after hyaluronic acid viscosupplementation in Osteoarthritis patients receiving SYNVISC-ONE® injection
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 Outcome Measures

Detection of Synovial fluid tribological properties through interferometry
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
Based on Raman spectroscopy
Detection of dried drops physicochemical index
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
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
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
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
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
Responder criteria for osteoarthritis clinical trials will be based on the questionnaires describe above.
Tolerance to the product
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

Full Information

First Posted
March 10, 2020
Last Updated
April 21, 2022
Sponsor
Pulsalys
Collaborators
Artialis
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1. Study Identification

Unique Protocol Identification Number
NCT04321668
Brief Title
Innovative Tool to Analyse Synovial Fluid of Patients With Knee Ostearthritis After IA Injection of Synvisc-one®
Acronym
RESYF
Official Title
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
Interventional

2. Study Status

Record Verification Date
April 2022
Overall Recruitment Status
Completed
Study Start Date
February 12, 2020 (Actual)
Primary Completion Date
October 1, 2021 (Actual)
Study Completion Date
February 15, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pulsalys
Collaborators
Artialis

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 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®.
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®.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Knee Osteoarthritis, Intra-Articular Injection
Keywords
Osteoarthritis, food supplement, SYNVISC, Synovial Fluid analysis

7. Study Design

Primary Purpose
Supportive Care
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Model Description
Proof of Concept (PoC), monocentric, non-comparative, interventional trial
Masking
None (Open Label)
Allocation
N/A
Enrollment
13 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Injection of SYNVISC-ONE
Arm Type
Other
Arm Description
Patients suffering from symptomatic knee osteoarthritis (OA), receiving intra-articular (IA) injection of SYNVISC-ONE® (Hylan G-F 20; 10 mL single-injection viscosupplement)
Intervention Type
Device
Intervention Name(s)
Synvisc-One
Other Intervention Name(s)
SYNVISC, Hylan G-F 20
Intervention Description
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
Primary Outcome Measure Information:
Title
Detection of variation of the composition of Synovial Fluid after hyaluronic acid viscosupplementation in Osteoarthritis patients receiving SYNVISC-ONE® injection
Description
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
Time Frame
6 months (between T0 and T6 visit)
Secondary Outcome Measure Information:
Title
Detection of Synovial fluid tribological properties through interferometry
Description
Topography measurement (3D tribological examination) will be performed using white light interferometry (smartWLI-microscope, GBS mbH, Germany) on the periphery of the drops.
Time Frame
6 months (between T0 and T6 visit)
Title
Detection of Synovial fluid molecular structural and chemical changes using a Raman confocal microscope
Description
Based on Raman spectroscopy
Time Frame
6 months (between T0 and T6 visit)
Title
Detection of dried drops physicochemical index
Description
Based on surface of dried drops and Raman ratios
Time Frame
6 months (between T0 and T6 visit)
Title
Variation of Visual Analogue Scale for the mean knee pain at rest and while walking over the last month
Description
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.
Time Frame
6 months (between T0 and T6 visit)
Title
Variation of Knee injury and Osteoarthritis Outcome Score using a self-administered questionnaire
Description
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.
Time Frame
6 months (between T0 and T6 visit)
Title
Variation of Visual Analogue Scale for patient global assessment of disease activity
Description
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.
Time Frame
6 months (between T0 and T6 visit)
Title
Determination of Semi-quantitative Whole ORgan Magnetic Imaging Score score of the joint
Description
MRI Imaging will be analyzed for WORMS by central reading in order to find correlation between the Imaging and the synovial fluid composition.
Time Frame
At baseline visit (T0)
Title
Responder rate to treatment defined as changes in knee pain and/or knee function and/or patients disease activity according to OMERACT OARSI criteria
Description
Responder criteria for osteoarthritis clinical trials will be based on the questionnaires describe above.
Time Frame
6 months (between T0 and T6 visit)
Title
Tolerance to the product
Description
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
Time Frame
6 months (between T0 and T6 visit)
Other Pre-specified Outcome Measures:
Title
Correlation at each timepoint between Synovial fluid composition and osteoarthritis biological markers (optional)
Description
Monitor the cartilage degeneration by determining the serum level of OA biomarkers through immunoassay (optional)
Time Frame
6 months (between T0 and T6 visit)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
40 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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: Related to the OA pathology Recent macro-trauma (< 6 months) of the knee responsible of the symptomatic knee. Micro-trauma are allowed according the Investigator's discretion 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 Related to treatment 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 anti-vitamin K (such as coumarinic) before injection 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 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 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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jean-Emile Dubuc, MD
Organizational Affiliation
Cliniques Universitaires Saint-Luc UCL
Official's Role
Principal Investigator
Facility Information:
Facility Name
Centre Medical Chant d'Oiseau
City
Woluwe-Saint-Pierre
State/Province
Bruxelles
ZIP/Postal Code
1150
Country
Belgium
Facility Name
Hopital Delta, CHIREC
City
Auderghem
ZIP/Postal Code
1160
Country
Belgium
Facility Name
Cliniques Universitaires Saint Luc - UCL
City
Woluwe-Saint-Pierre
Country
Belgium

12. IPD Sharing Statement

Plan to Share IPD
No

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

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