Effects of Different Collagen Formulations on Knee Osteoarthritis

August 30, 2026 updated by: Cihangir Türemiş

Comparison of the Effects of Different Collagen Formulations on Pain, Function, and Quality of Life in Patients With Knee Osteoarthritis: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial

The purpose of this study is to evaluate and compare the effects of two different collagen supplement formulations on pain, physical function, and overall quality of life in adults with knee osteoarthritis.

Knee osteoarthritis is a common joint disease characterized by cartilage degeneration, which leads to chronic pain and reduced mobility. While collagen supplements are frequently used to support joint health, their clinical effectiveness is usually measured using traditional pain scales. However, osteoarthritis pain is complex and multidimensional, often involving different patterns (such as constant or intermittent pain) and central neurological sensitization. This study aims to use a holistic approach to understand how collagen supplements affect these complex pain experiences using comprehensive patient-reported outcome measures.

Participants in this study will be adults between the ages of 35 and 65 who have been diagnosed with unilateral knee osteoarthritis (Kellgren-Lawrence grade 2 or 3).

Participants will be randomly assigned to one of three groups:

Hydrolyzed Collagen Group: Participants will consume a daily sachet containing 10 grams of enzymatically hydrolyzed bovine collagen peptide.

Bioactive Collagen Peptide Group: Participants will consume a daily sachet containing 5 grams of lower molecular weight bovine collagen peptide mixed with 5 grams of maltodextrin.

Placebo Group: Participants will consume a daily sachet containing 10 grams of maltodextrin (with no active collagen or protein), matching the active supplements in taste, smell, and appearance.

All participants will take their assigned supplement once daily for 8 weeks. To ensure unbiased results, the study is double-blind, meaning neither the participants nor the research staff evaluating the outcomes will know which group a participant is in.

Researchers will assess the participants at the beginning of the study (baseline) and at the end of the 8-week intervention. Assessments will be conducted using various established questionnaires to measure joint stiffness, physical limitations, general quality of life, and specific pain patterns, including central sensitization.

The study will be conducted at the Orthopedics and Traumatology Clinic of Cesme Alper Cizgenakat State Hospital in Türkiye. By looking beyond traditional clinical scales, this research aims to provide a deeper understanding of how different collagen formulations can improve the daily lives and complex pain symptoms of patients living with knee osteoarthritis.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Background and Rationale Knee osteoarthritis (OA) is a prevalent joint disorder characterized by progressive cartilage degeneration, chronic pain, and loss of function. While conservative management often includes dietary supplements such as hydrolyzed collagen and bioactive collagen peptides to support joint biology, clinical evaluations of these supplements are typically limited to traditional, unidimensional pain and function scales. Recent literature, however, emphasizes that OA pain is highly complex, involving peripheral nociceptive mechanisms, constant and intermittent pain patterns, and central neurological sensitization. Addressing a significant methodological gap in the literature, this study extends beyond standard scales by incorporating comprehensive Patient-Reported Outcome Measures (PROMs) to capture the holistic pain experience, including central sensitization, in patients with knee OA.

Study Procedures and Blinding This is a single-center, randomized, double-blind, placebo-controlled, parallel-group clinical trial. Following the baseline clinical and radiographic evaluation (Kellgren-Lawrence grading performed by an experienced orthopedic surgeon), eligible participants will be randomly allocated to one of three intervention arms using computer-assisted block randomization.

To ensure strict quadruple blinding (participant, care provider, investigator, and outcomes assessor), allocation concealment will be achieved using independently coded, opaque packaging. The active interventions (two different collagen formulations) and the placebo (maltodextrin-based) will be formulated to be entirely identical in appearance, color, smell, taste, and volume.

Intervention Administration and Monitoring Participants will be instructed to consume their assigned single-use sachet once daily between 13:00 and 15:00 for the entire 8-week intervention period. Patients will be advised to maintain their habitual physical activity levels throughout the study. Rescue analgesics are permitted if necessary for severe pain; however, the use of these medications must be strictly suspended at least 48 hours prior to any clinical evaluation session to avoid masking the outcomes. Adherence to the supplement regimen, rescue medication usage, and any potential adverse events will be continuously monitored via daily follow-up cards filled out by the participants. A minimum adherence rate of 95% is mandatory; participants failing to meet this threshold will be excluded from the final analysis.

Sample Size and Statistical Analysis Plan An a priori power analysis was conducted using G*Power software to determine the required sample size. Based on a Mixed-Design ANOVA model (group × time interaction) aiming for a moderate effect size (Cohen's f = 0.25), an alpha level of 0.05, and 80% statistical power, a minimum of 42 participants was required. To account for potential dropouts, a total of 45 patients (15 per group) will be enrolled.

Statistical analyses will be executed using R software under a Per-Protocol (PP) framework. Data normality will be assessed using the Shapiro-Wilk test. A Mixed-Design ANOVA will be employed to evaluate the main effects and the group-by-time interactions. Significant interactions will be further analyzed with post-hoc pairwise comparisons utilizing the Bonferroni correction. Effect sizes will be reported using Cohen's d for pairwise comparisons and partial eta squared (reported as η²p) for variance analyses, along with corresponding lower and upper bounds (LB/UB). Statistical significance is set at p < 0.05.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
45

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

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

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Adults aged between 35 and 65 years.
  • Clinical and radiographic diagnosis of primary knee osteoarthritis according to the American College of Rheumatology (ACR) criteria.
  • Radiographic severity of Kellgren-Lawrence grade 2 or 3 in the affected knee.
  • Experiencing chronic knee pain for at least the last 3 months.
  • Willingness to refrain from starting any new dietary supplements or physical therapy programs during the 8-week study period.
  • Ability to read, understand, and provide written informed consent, as well as independently complete the patient-reported outcome questionnaires.

Exclusion Criteria:

  • Severe knee osteoarthritis (Kellgren-Lawrence grade 4) or mild/doubtful osteoarthritis (Kellgren-Lawrence grade 0-1).
  • History of intra-articular injections (corticosteroid, hyaluronic acid, PRP, stem cell, etc.) to the affected knee within the last 6 months.
  • Routine use of other joint health supplements (e.g., glucosamine, chondroitin, MSM, other collagen products) within the last 3 months.
  • History of major lower extremity surgery, major trauma, or previous ligament reconstruction (e.g., ACL reconstruction) on the affected knee.
  • Presence of systemic inflammatory joint diseases (e.g., rheumatoid arthritis, ankylosing spondylitis, gout).
  • Known allergy, hypersensitivity, or intolerance to bovine (beef) products or maltodextrin.
  • Current pregnancy or lactation.
  • Severe neurological, psychiatric, or cognitive disorders that would prevent accurate completion of the pain and central sensitization questionnaires.

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: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Hydrolyzed Collagen
Participants in this arm will receive a daily single-use sachet containing 10 grams of enzymatically hydrolyzed bovine collagen peptide. The supplement is to be dissolved in water and consumed once daily for 8 weeks.
Dietary supplement: 10g Hydrolyzed Collagen
A single-use sachet containing 10 grams of enzymatically hydrolyzed bovine collagen peptide. To be dissolved in water and taken orally once daily for 8 weeks.
Experimental: Bioactive Collagen Peptide
Participants in this arm will receive a daily single-use sachet containing 5 grams of lower molecular weight bovine collagen peptide mixed with 5 grams of maltodextrin. The supplement is to be dissolved in water and consumed once daily for 8 weeks.
Dietary supplement: 5g Bioactive Collagen Peptide
A single-use sachet containing 5 grams of lower molecular weight bovine collagen peptide mixed with 5 grams of maltodextrin. To be dissolved in water and taken orally once daily for 8 weeks.
Placebo Comparator: Placebo
Participants in this arm will receive a daily single-use sachet containing 10 grams of maltodextrin, with no active collagen or protein. The placebo is completely identical to the active supplements in appearance, color, smell, and taste. It is to be dissolved in water and consumed once daily for 8 weeks.
Other: Placebo (Maltodextrin)
A single-use sachet containing 10 grams of maltodextrin with no active ingredients, completely matching the active supplements in appearance, color, smell, and taste. To be taken orally once daily for 8 weeks.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Total Score
Time Frame: Baseline (Week 0) and End of Intervention (Week 8)
The WOMAC is a self-administered questionnaire used to evaluate pain, stiffness, and physical function in patients with knee osteoarthritis. It consists of 24 items divided into three subscales: Pain (5 items), Stiffness (2 items), and Physical Function (17 items). The total score ranges from 0 to 96. Higher scores indicate worse symptom severity, greater pain, and more physical disability. A decrease in the score indicates an improvement in the patient's condition.
Baseline (Week 0) and End of Intervention (Week 8)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change in Visual Analog Scale (VAS) for Pain
Time Frame: Baseline (Week 0) and End of Intervention (Week 8)
Pain intensity will be measured using a 10-cm Visual Analog Scale (VAS). The scale is anchored by "no pain" (score of 0) and "worst imaginable pain" (score of 10). Higher scores indicate greater pain severity. A decrease in the score indicates pain relief.
Baseline (Week 0) and End of Intervention (Week 8)
Change in Central Sensitization Inventory (CSI) Score
Time Frame: Baseline (Week 0) and End of Intervention (Week 8)
The CSI is a validated screening instrument used to identify and quantify symptoms related to central sensitization. It consists of 25 items scored on a 5-point Likert scale, with a total score ranging from 0 to 100. Higher scores indicate a higher degree of central sensitization symptom severity. A decrease in the score indicates an improvement.
Baseline (Week 0) and End of Intervention (Week 8)
Change in Intermittent and Constant Osteoarthritis Pain (ICOAP) Questionnaire Score
Time Frame: Baseline (Week 0) and End of Intervention (Week 8)
The ICOAP is an 11-item questionnaire designed to comprehensively evaluate both constant and intermittent pain experiences in osteoarthritis. It provides a constant pain subscale, an intermittent pain subscale, and a total pain score. Scores are normalized to range from 0 to 100. Higher scores represent more severe constant and intermittent pain. A decrease in the score indicates symptomatic improvement.
Baseline (Week 0) and End of Intervention (Week 8)

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Cihangir Türemiş

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Cihangir Türemiş, Dr., Cesme Alper Cizgenakat State Hospital, İzmir/Türkiye

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 (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 1, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
May 1, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 1, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 30, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 30, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 2, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 2, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 30, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • SNU6143

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

De-identified individual participant data (IPD) that underlie the results reported in this article will be made available upon reasonable request to the principal investigator, following the publication of the study. Data will be shared strictly for academic and non-commercial research purposes.

IPD Sharing Time Frame

Data and supporting information will become available beginning 6 months after the publication of the primary research article and ending 36 months following the publication date.

IPD Sharing Access Criteria

De-identified individual participant data, study protocol, statistical analysis plan, and analytic codes will be shared with researchers who provide a methodologically sound proposal for non-commercial academic research. Proposals should be directed to the Principal Investigator via email. To gain access, data requestors will need to sign a data access agreement. Data will be provided via a secure file transfer system upon approval of the request.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ANALYTIC_CODE

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

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.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings