To Look at the Characteristics of Synovial Fluid and Cartilage Matrix in Osteoarthritic Knee After Hyaluronic Acid Injection

Quantifications of Biochemical Changes of Synovial Fluid and Cartilage Matrix in Osteoarthritic Knee After Hyaluronic Acid Injection Using Novel MRI (Magnetic Resonance Imaging) and NMR (Nuclear Magnetic Resonance) Techniques

The purpose of this study is to identify novel imaging markers for characterizing the biochemical profiles in synovial fluid and cartilage matrix in OA knee joints after intra-articular HA (Euflexxa) injection using high field NMR and MRI techniques.

We hypothesize that:

1. High-field HRMAS NMR spectroscopy will provide sensitive measures for biochemical changes within knee synovial fluid after HA injection;
2. Baseline HRMAS spectroscopy, in particular N-acetyl peaks, as well as early changes of glutamate will predict patient response of pain relief after HA injection;
3. MR cartilage T1p and T2 quantifications will provide sensitive measures for biochemical changes within knee cartilage matrix after HA injection. Specifically cartilage T1p and T2 will decrease in patients who respond to the treatment, indicating potential beneficial effects of HA injection to cartilage preservation.

Study Overview

• Status: Completed
• Conditions: Knee Osteoarthritis
• Intervention / Treatment: Drug: Euflexxa; Device: Magnetic Resonance Imaging (MRI)

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94107
      • UCSF - China Basin Imaging Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age 18 to 80 years
• Symptomatic knee OA as defined by the American College of Rheumatology criteria
• Kellgren-Lawrence grade I, II or III on prior x-rays (take within 6 months of screening visit)
• knee pain score >40 mm on a 100 mm visual analogue scale for > 15 days in the last month
• NSAIDs permitted if the dose has been stable for at least one month prior to baseline and stays stable during the study
• Have been recommended for Euflexxa treatment by physician
• Knee effusion based on clinical exam or imaging

Exclusion Criteria:

• Any contraindication to MRI (pregnancy, metallic fragments in the eyes, vascular clips, Pacemakers etc)
• History of knee replacement
• Known sensitivity or allergy to any component of Euflexxa
• Inflammatory arthritis
• Previously received viscosupplementation therapy within 6 months of study enrollment
• Intra-articular injection of corticosteroid to study joint within the past 3 months
• Arthroscopic or open surgery within the previous 12 months or planned surgery to the study joint
• Concomitant medications of oral/parenteral corticosteroids
• Morbid obesity defined as body mass index (BMI) >40 kg/m2
• Active malignancy; an active systemic infection; recent high impact or high energy trauma (clinically defined) to the study joint
• Large knee effusion based on clinical exam or imaging

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Euflexxa; EUFLEXXA® is a hyaluronate hydrogel produced from bacteria, in a phosphate-buffered saline solution. It is given as a three week treatment regimen. It involves injecting of 2cc or 20mg intra-articularly once per week.	Drug: Euflexxa; Euflexxa will be injected weekly for 3 consecutive weeks on the knee joint.; Other Names: hyaluronic acid injection; Device: Magnetic Resonance Imaging (MRI); MRI of the knee will be acquired during baseline (a week prior to the treatment), follow up visit 1 (1 week after treatment) and follow up visit 2 (3 months after treatment).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To Identify Imaging Markers for Characterizing the Biochemical Profiles in Synovial Fluid and Cartilage in Knee OA After HA Injection	The study will demonstrate the feasibility of using MRI and NMR techniques to quantify biochemical changes in synovial fluid and cartilage matrix in OA knees after HA injection.	3 months

Secondary Outcome Measures

Outcome Measure	Time Frame
To Quantify Synovial Fluid Biochemical Changes Using High Field HRMAS NMR Spectroscopy	3 months

Other Outcome Measures

Outcome Measure	Time Frame
To Quantify Cartilage Matrix Changes Using MR T1p ad T2 Mapping at 3T MRI	3 months

Collaborators and Investigators

• Sponsor: University of California, San Francisco
• Collaborators: Ferring Pharmaceuticals
• Investigators: Principal Investigator: Xiaojuan Li, PhD, University of California, San Francisco

Study record dates

Study Major Dates

• Study Start: August 1, 2013
• Primary Completion (Actual): November 1, 2016
• Study Completion (Actual): January 1, 2017

Study Registration Dates

• First Submitted: July 5, 2013
• First Submitted That Met QC Criteria: July 10, 2013
• First Posted (Estimate): July 11, 2013

Study Record Updates

• Last Update Posted (Actual): November 18, 2020
• Last Update Submitted That Met QC Criteria: October 26, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: knee osteoarthritis (OA); hyaluronic acid injection
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee; Physiological Effects of Drugs; Immunologic Factors; Protective Agents; Adjuvants, Immunologic; Viscosupplements; Hyaluronic Acid
• Other Study ID Numbers: Ferring-Euflexxa

Drug and device information, study documents

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