Effect of Zilretta Injection

May 18, 2022 updated by: University of North Carolina, Chapel Hill

Effect of ZILRETTA Injection on Neuromuscular Function, Gait Biomechanics and Physical Performance

The purpose of this study is to examine the pre-post effects of a single ZILRETTA knee injection on physiological measures of self-reported pain and disability, physical performance, and physical activity in individuals with knee osteoarthritis (OA). The investigators will recruit 35 symptomatic knee OA patients for this study. All data will be collected prior to injection (baseline), as well as at 4 (post 1) and 8-week follow-ups (post 2).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Individuals with knee osteoarthritis (OA) demonstrate significant physical disability which leads to diminished physical activity, a lesser quality of life, as well as a higher risk of inactivity related comorbidities including mortality. This is thought to be caused by an inability to voluntarily activate your quadriceps muscle due, in part, to knee joint swelling and joint-related pain. Incomplete muscle activation causes quadriceps weakness.

Individuals with quadriceps weakness exhibit changes in their walking biomechanics which is associated with diminished physical function and lesser physical activity in those with knee OA. Therefore, it is critical to develop interventions that target mechanisms causing decreased quadriceps activation in order to restore optimal walking biomechanics and improve physical activity.

The ZILRETTA knee injection is an FDA approved, extended release corticosteroid for in patients with knee osteoarthritis and has been shown to reduced knee pain for 3 months in approximately 70% of patients. Currently, there are no studies that have examined ZILRETTA's objective effectiveness on physical activity, biomechanics, and performance tests in patients who have received an injection.

The overall purpose of the current study is to examine the effect of a ZILRETTA knee injection on functional and performance tests including quadriceps neuromuscular activation, quadriceps strength, walking gait biomechanics, and a battery of physical performance outcomes at 4 and 8-weeks following injection in 35 individuals with knee OA.

Study Type

Interventional

Enrollment (Actual)

35

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27516
        • MOTION Science Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

40 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Full Inclusion Criteria:

  • Male or female between the ages of 40 and 75 years old who:
  • Exhibit symptomatic knee OA, defined as a normalized WOMAC function subscale score >31(out of 100 points, indicating highest degree of dysfunction)
  • Have radiographic evidence of tibiofemoral OA (2-4 on the Kellgren-Lawrence scale)
  • Provide written informed consent and the ability to comply with the requirements of the study.

  • Be willing to abstain from use of the following protocol-restricted medications during the study:

    • Corticosteroid injections into the knee or any lower extremity joint will be restricted for 3 months prior to the screening visit (based on the drug half-life) and throughout the entirety of the study period including the 8-week follow-up test. Information about when the latest corticosteroid injection occurred for each participant prior to screening in order to determine when each participant can attend the screening visit.
    • Hyaluronic acid injections into the knee or any lower extremity joint will be restricted for 6 months prior to the screening visit (based on the drug half-life) and throughout the entirety of the study period including the 8-week follow-up test. Information about when the latest hyaluronic acid injection occurred for each participant prior to screening in order to determine when each participant can attend the screening visit.
    • Prescription Depressants (Examples: opiates and opioids, barbiturates, tranquilizers and benzodiazepines) will be restricted 4-weeks prior to screening and throughout the study period as these medications may affect the neuromuscular function.
    • Prescription Stimulants (Example: amphetamines) will be restricted 4-weeks prior to screening and throughout the study period as these medications may affect the neuromuscular function
    • Non-steroidal anti-inflammatory drugs (NSAIDs) will be restricted 24 hours prior to screening or follow-up testing sessions. NSAID use will be tracked and patients instructed not to change their NSAIDs usage during the 8-weeks of the study.
    • Acetaminophen will be restricted 24 hours prior to screening or follow-up testing sessions. Acetaminophen use will be tracked and patients instructed not to change their Acetaminophen usage during the 8-weeks of the study.

Full Exclusion Criteria:

Potential participants meeting any of the following criteria (based on the electronic medical record or in laboratory screening) will be excluded if they:

  • Are hypersensitive to triamcinolone acetonide, corticosteroids or any components of the product
  • Have other intra-articular investigational drug/biologic use in the previous 6-months
  • Have been diagnosed with a cardiovascular condition restricting exercise
  • Have had a corticosteroid injection in the involved knee in the previous 3-months or hyaluronic acid injection in the involved knee in the previous 6-months
  • Have a pacemaker
  • Have a neurodegenerative condition
  • Have rheumatoid arthritis
  • Have diabetes
  • Have cancer
  • Have a neural sensory dysfunction over the knee
  • Have a body mass index (BMI) over 35
  • Have a history of lower extremity orthopaedic surgery in the past year
  • Have a history of a traumatic knee injury in the past 6 months
  • Have any history of total knee arthroplasty in either extremity
  • Have a diagnosed, non-reconstructed knee ligament tear
  • Need an assistive device to walk
  • Are currently pregnant or planning to become pregnant while enrolled in the study
  • Are taking medications that can react harmfully with injected corticosteroids

NOTE: Individuals that have bilateral knee OA will not be excluded unless they meet another exclusion criteria. In case a patient needs an injection in both knees, they will be excluded. Only one knee will be injected for this study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: ZILRETTA Injection
All patients upon enrolling in the study will receive a single 5 mL injection of 32 mg ZILRETTA into the affected knee joint.
Drug: Triamcinolone Acetonide Extended-Release Injectable Suspension
A single ZILRETTA® (triamcinolone acetonide extended-release injectable suspension) intra-articular knee injection.
Other Names:
  • Zilretta Injectable Product

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage Change in Mean Maximal Quadriceps Strength as Measured by the Maximal Isometric Voluntary Contractions Normalized to Body Weight from Baseline to the 8-week follow-up.
Time Frame: Baseline and 8-week follow-up
Quadriceps strength was measured in Newton Meters normalized to body weight of the individuals. Strength was assessed in 90 degrees of knee flexion.
Baseline and 8-week follow-up
Percentage Change in Mean Voluntary Quadriceps Activation as Measured by the Central Activation Ratio Expressed as a Percent of Full Activation from Baseline to the 8-week follow-up.
Time Frame: Baseline and 8-week follow-up
The investigators assessed voluntary quadriceps central activation ratio as a representative variable of lower extremity neuromuscular activation using the supra imposition technique. Quadriceps central activation ratio has been demonstrated to be significantly decreased in knee osteoarthritis (OA) compared to healthy, matched controls, and the investigators have reported acceptable measurement reliability (ICC2,k = 0.85)
Baseline and 8-week follow-up
Percentage Change in Mean Knee Flexion Angle During Walking Gait Measured in Degrees of Knee Flexion from Baseline to the 8-week follow-up.
Time Frame: Baseline and 8-week follow-up
The peak Knee Flexion Angle was calculated using using inverse dynamics calculations in the first 50% of the stance phase of gait and during self selected gait speed.
Baseline and 8-week follow-up
Percentage Change in Mean Internal Knee Extension Moment During Walking Gait Measured in Nm/ Body Weight*m from Baseline to the 8-week follow-up.
Time Frame: Baseline and 8-week follow-up
The peak internal knee extension moment was calculated using using inverse dynamics calculations in the first 50% of the stance phase of gait and normalized to the Body Weight* height (m) of the individual during self selected gait speed.
Baseline and 8-week follow-up
Percentage Change in Mean of Self-reported Disability Score as Measured by the Western Ontario and McMasters Universities Index from Baseline to the 8-week follow-up.
Time Frame: Baseline and 8-week follow-up
The Western Ontario and McMasters Universities Index is reliable and valid measure of self reported disability. The physical function consists of 17 items and asks about the magnitude of difficulty when ascending and descending stairs, rising from sitting, standing, bending, walking, getting in / out of a car, shopping, putting on and taking off socks, rising from bed, lying in bed, getting in and out of the bath, sitting, getting on and off the toilet, completing heavy household duties, and completing light household duties. Each item is presented in a 5 point Likert-type format and uses the following descriptors for possible answer choices none, mild moderate, severe, and extreme. Each descriptor corresponds to an ordinal scale of 0-4. The scores are summed for the items in each subscale, with total possible ranges as 0-68. Higher scores on the WOMAC indicate greater amounts of functional limitations.
Baseline and 8-week follow-up
Percentage Change in mean of self-reported Disability Score as Measured by the Knee Injury and Osteoarthritis Outcome Score from Baseline to the 8-week follow-up.
Time Frame: Baseline and 8-week follow-up
The Knee Injury and Osteoarthritis Outcomes Score (KOOS) consists of five subscales: Pain (9 items), Symptoms (7 items), Function in Activities of Daily Living (17 items), Function in Sport and Recreation (5 items) and Knee Related Quality of Life (4 items). Each item is presented in a 5 point Likert-type format that ranges from 0 (no problems) to 4 (extreme problems). Totals from each subscale are transformed to a 0-100 score. Lower scores on the KOOS indicate greater amounts of functional limitations.
Baseline and 8-week follow-up
Percentage Change in Physical Activity Scale for the Elderly from baseline to the 8-week follow-up.
Time Frame: Baseline and 8-week follow-up
Physical Activity Scale for the Elderly (PASE) scores are calculated from weights and frequency values for each of 12 types of activity. Responses to the first question about sitting activities are not scored. The scale is continuous with higher scores indicating greater physical activity.
Baseline and 8-week follow-up
Percentage Change in 30-s chair-stand test from Baseline to the 8-week follow-up.
Time Frame: Baseline and 8-week follow-up
The number of times that an individual can sit and stand in 30 seconds.
Baseline and 8-week follow-up
Percentage Change in 20 meter fast-paced walk test from Baseline to the 8-week follow-up.
Time Frame: Baseline and 8-week follow-up
The investigators will time the amount of seconds it takes to walk 20 meters.
Baseline and 8-week follow-up
Percentage Change in Stair-climb test from Baseline to the 8-week follow-up.
Time Frame: Baseline and 8-week follow-up
The investigators will time the amount of seconds it takes to walk up and down a flight of stairs.
Baseline and 8-week follow-up
The percentage change in steps per day from Baseline to the 8-week follow-up.
Time Frame: Baseline and 8-week follow-up
Physical activity will be measured in the form of steps per day using an ActiGraph accelerometer. Participants will wear the ActiGraph for 7 days following each testing session.
Baseline and 8-week follow-up

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of North Carolina, Chapel Hill

Collaborators

Flexion Therapeutics, Inc.

Investigators

  • Principal Investigator: Brian Pietrosimone, PhD, ATC, University of North Carolina, Chapel Hill

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 1, 2020

Primary Completion (Actual)

January 10, 2022

Study Completion (Actual)

January 10, 2022

Study Registration Dates

First Submitted

February 5, 2020

First Submitted That Met QC Criteria

February 5, 2020

First Posted (Actual)

February 7, 2020

Study Record Updates

Last Update Posted (Actual)

May 20, 2022

Last Update Submitted That Met QC Criteria

May 18, 2022

Last Verified

March 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 19-3562

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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