Cross-linked Hyaluronic Acid in Knee Osteoarthritis

February 24, 2026 updated by: Seyda Ersahan, DDS, PhD, Istanbul Medipol University Hospital

Clinical Superiority of Cross-linked Hyaluronic Acid in Knee Osteoarthritis: Sustained Efficacy on Pain and Function

Knee Osteoarthritis (Knee OA) leads to pain and loss of function, especially in recreational athletes. While hyaluronic acid (HA) injections are a common part of conservative treatment, comparative data on the efficacy of straight-chain (ST-HA) versus cross-linked (CL-HA) formulations remain limited. Therefore, the aim of this study was to compare the 6-month efficacy of a single dose of CL-HA versus two doses of ST-HA regarding pain, stiffness, and joint function in recreational athletes aged 50-70 with Kellgren-Lawrence grade 2-3 Knee OA refractory to pharmacological treatment.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This retrospective observational study included 88 recreational athletes (CL-HA: n=44, ST-HA: n=44). All participants received either a single dose of CL-HA or two doses of ST-HA administered 4 weeks apart. Patients were comparatively evaluated pre-treatment and at 1, 3, and 6 months post-treatment using the WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) and VAS scores.

Study Type

Observational

Enrollment (Actual)

88

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

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

  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Sampling Method

Non-Probability Sample

Study Population

This retrospective observational study was conducted in a multicenter manner and included recreational athletes aged between 50 and 70 years who applied to Medipol Esenler Hospital and Republic of Turkey Ministry of Health Erenköy Physical Therapy and Rehabilitation Hospital due to knee pain and were diagnosed with gonarthrosis between January 2021 and December 2024.

Description

Inclusion Criteria: Inclusion criteria: Recreational athletes aged 50-70 years; participants must not have received any injections or undergone physical therapy or rehabilitation in the last 3 months; and symptomatic cases of Kellgren-Lawrence stage 2-3 knee osteoarthritis and failure of pharmacological treatment.

Exclusion Criteria: Inflammatory disease, active rheumatic disease, malignancy, bleeding diathesis, peripheral neuropathy, BMI >30, grade 4 gonarthrosis, regular NSAID use, previous knee surgery, local infection at the procedure site, corticosteroid injection at the procedure site within the last 3 months, systemic corticosteroid use within the last 2 weeks, immunosuppressant use or immunodeficiency within the last 6 weeks, and any local or systemic osteoarthritis-related treatments (therapeutic exercises, physical therapy, other injections, NSAIDs, etc.) within the last 6 months.

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Patients were comparatively evaluated pre-treatment and at 1, 3, and 6 months post-treatment using the WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) score.
Time Frame: Patients were comparatively evaluated pre-treatment and at 1, 3, and 6 months post-treatment
Minimal value is 0, while maximum value is 96.
Patients were comparatively evaluated pre-treatment and at 1, 3, and 6 months post-treatment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Patients were comparatively evaluated pre-treatment and at 1, 3, and 6 months post-treatment using the VAS score.
Time Frame: Patients were comparatively evaluated pre-treatment and at 1, 3, and 6 months post-treatment
Minimal value is 0, while maximum value is 10.
Patients were comparatively evaluated pre-treatment and at 1, 3, and 6 months post-treatment

Collaborators and Investigators

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

Sponsor

Istanbul Medipol University Hospital

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)

January 2, 2021

Primary Completion (Actual)

December 31, 2024

Study Completion (Actual)

May 31, 2025

Study Registration Dates

First Submitted

November 17, 2025

First Submitted That Met QC Criteria

November 17, 2025

First Posted (Actual)

November 21, 2025

Study Record Updates

Last Update Posted (Actual)

February 27, 2026

Last Update Submitted That Met QC Criteria

February 24, 2026

Last Verified

February 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • E-10840098-202.3.02-5817

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

After publication in a journal, I will share all IPD that underlie results in a publication

IPD Sharing Time Frame

Beginning immediately after publicaiton

IPD Sharing Access Criteria

I will consider review requests for IPD sharing and how they will be reviewed.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

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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