Knee OsteoarthritisNCT04998188
Hydrolyzed Collagen Formulation vs Placebo in Knee Osteoarthritis
A study testing Collagen in people with Knee Osteoarthritis, run by Istituto Ortopedico Rizzoli at 1 site in Italy.
Trial summary
The aim of the study is to compare the 6 months clinical outcome of the treatment with a single intra-articular collagen injection versus a single placebo (saline solution) infiltration in the infiltrative treatment of knee osteoarthritis. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Knee Osteoarthritis
- What is being tested?
- Collagen
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 204 participants
- Where
- 1 siteItaly
- Study dates
- 16 Feb 2022to Dec 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Unilateral involvement;
- Signs and symptoms of degenerative pathology of knee cartilage;
- Radiographic and MRI signs of degenerative pathology of the knee cartilage (Kellgren-Lawrence 1-4 grades);
- Failure, defined as the persistence of symptoms, after at least one course of conservative treatment (pharmacological, physiotherapeutic or infiltrative treatment);
- Ability and consent of patients to actively participate in clinical follow-up;
Who cannot join
- Patients who have undergone intra-articular injections of another substance in the previous 6 months;
- Patients undergoing knee surgery within the previous 12 months;
- Patients with malignant neoplasms;
- Patients with rheumatic diseases;
- Patients with diabetes;
- Patients with hematologic diseases (coagulopathies);
Show all 13Show fewer
- Patients on anticoagulant therapy;
- Patients with metabolic disorders of the thyroid gland;
- Patients abusing alcoholic beverages, drugs or medications;
- Body Mass Index > 35;
- Pregnant or lactating women.
- Patients with established hypersensitivity to bovine collagen or vitamin C.
- Patients with joint or peri-articular infections, emarto, erythema, or psoriatic patches in the knee joint area
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Alessandro Di Martino, MD contact
Italy1 site, 1 recruiting
- Recruiting
Istituto Ortopedico Rizzoli
Bologna, 40136
Alessandro Di Martino, MD, 6366567 ext. 051, alessandro.dimartino@ior.it
Roberta Licciardi, MSc, 6366567 ext. 051, roberta.licciardi@ior.it
About this study
Official title: Hydrolyzed Collagen Formulation Versus Placebo in the Treatment of Degenerative Knee Cartilage Injuries
The aim of the study is to compare the 6 months clinical outcome of the treatment with a single intra-articular collagen injection versus a single placebo (saline solution) infiltration in the infiltrative treatment of knee osteoarthritis. The evaluation will be performed through clinical, subjective and objective assessments.
Read the detailed description
204 patients affected by knee osteoarthritis will be included in a double-blinded randomized controlled trial. Patients in the experimental group will be treated with a single intra-articular injection of collagen (solution of low molecular weight peptides derived from hydrolyzed collagen) instead patients in the control arm, will be treated with a single intra-articular injection of placebo (saline solution). All patients will be evaluated by clinical examination before the infiltrative procedure and they will follow-up at 1,3,6 months. During the follow-up visits ,will be evaluated the inflammatory status of the knee by thermographic assessment and questionnaires, filled out by patients, will be utilized for clinical evaluations. After 6 months, patients in the control arm (saline solution injection), have the possibility to cross-over into the treatment arm (collagen) in which case they will be followed for an additional 6 months.
- Conditions
- Knee Osteoarthritis
- Being tested
- Collagen, Placebo (saline solution)
- Keywords
- knee, knee osteoarthritis, collagen, collagen injection, osteoarthritis, placebo, Randomized controlled trial, double-blinded
- Medical subject headings
- Osteoarthritis, Knee, Osteoarthritis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CollagenProcedure or surgery
Patients will be treated with a single injection of collagen (2 ml) in the knee joint affected by osteoarthritis
Placebo (saline solution)Procedure or surgery
Patients will be treated with a single injections of saline solution (2 ml) in the knee joint affected by osteoarthritis
| Study group | Role | What they receive |
|---|---|---|
| Collagen Injection | Experimental | This group of patients will be treated with single intra-articular injection of collagen. Receives: Procedure: Collagen |
| Placebo (saline solution) | Placebo comparator | This group of patients will be treated with single intra-articular injection of saline solution (placebo). At the 6-month follow-up visit, patients will be informed about the treatment received. Patients of this group can cross-over to the treatment arm after 6 months. Receives: Procedure: Placebo (saline solution) |
What is being measured
The primary outcome is the main question the study is designed to answer.
KOOS-Pain Score
KOOS-Pain Score is referred to a subscale of pain composed by 9 items. The score range considerate is 0-100.The score uses a 5-point Likert scale and each question is assigned a score from 0 to 4, where 0 indicates "no pain" and 4 "severe level of pain"
Measured: 6 months follow-up
Secondary outcomes (13)
IKDC-Subjective Score
This is a subjective, knee-specific rating scale that is considered one of the most reliable assessment tools in the evaluation of knee pathologies. All questions examines 3 categories: symptoms, sports activity, and knee function
Measured: baseline, 1 month, 3 months, 6 months follow-up
KOOS Score
KOOS SCORE consists of 5 subscales and covers: pain (9 items), symptoms (7 items, two of which are related to stiffness), functions and activities of daily living (17 items), physical function, sports and leisure activities (5 items) and quality of life in relation to the knee (4 items).
Each question is scored from 0 to 4, where 0 indicates "no difficulty" and 4 "severe difficulty. Score range 0-100 for each subscale
Measured: baseline, 1 month, 3 months, 6 months follow-up
WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) score
It's a standardized questionnaire to assess the condition of patients affected by knee osteoarthritis and includes assessment of pain, stiffness and physical functioning of the joints. It measures 5 items for pain (range 0-20), two for stiffness (range 0-8) and 17 for functional limitation (range 0-68) that relate mainly to activities of daily living. The score is normalized on a 0-100 scale. Higher values indicate a worse outcome.
Measured: baseline, 1 month, 3 months, 6 and 12 months follow-up
VAS-pain (Visual Analogue Scale)
VAS is a visual analogue scale consisting of a range scale (10 cm length), the ends of which correspond to "no pain" and "the strongest pain imaginable".
Measured: baseline, 1 month, 3 months, 6 months follow-up
EQ-VAS
EQ-VAS Is a visual analog scale that has a range of scores from 0 (worst imaginable health condition) to 100 (best imaginable health condition).
Measured: baseline, 1 month, 3 months, 6 months follow-up
EQ-5D (EuroQoL) Current Health Assessment
The EQ-5D profile, asks patients to classify their health based on self-assessed levels of problems ("no", "some", "extreme") on five dimensions.
Measured: baseline, 1 month, 3 months, 6 months follow-up
TegnerActivity Level Scale
Tegner activity level scale allows to know the level of physical activity carried out by the patients. Tegner's activity scale classifies the activity according to work and sports activities on a scale from 0 to 10. Zero represents disability because of knee problems and 10 represents soccer a national or international level
Measured: baseline, 1 month, 3 months, 6 months follow-up
Patient Acceptable Symptom State (PASS)
A tool to assess patient satisfaction in consideration of their current degree of pain, function, and daily activity. Patients can express if their state of health will be satisfying, answering "yes" or "no".
Measured: baseline, 1 month, 3 months, 6 months follow-up
Objective parameters -Range of motion
Evaluation of the Range of Motion for comparative analysis.
Measured: baseline, 1 month, 3 months, 6 months follow-up
Final treatment opinion
The patient should indicate satisfaction and relative degree with treatment at the end of the clinical trial (24 months follow-up). All patients will be able to indicate their health condition by choosing from this answers; "Full recovery", "much better", "somewhat better", "no change", "a little worse", "much worse".
Measured: 6 months follow-up
Ultrasound assessment
This examination is useful to do an initial assessment of possible meniscal extrusion in the interested knee joint.
Measured: Baseline
Thermographic evaluation of the inflammatory status of the knee joint
The evaluation will be performed through the use of a thermal imaging camera. The thermal camera will allow to detect even small variation of knee temperature thus comparing and recording any thermographic changes in the inflammatory state of the joint before and after treatment.
Measured: baseline, 1 month, 3 months, 6 months follow-up
Objective parameters - Circumferences
Bilateral trans- and supra- patellar circumferences measurement for comparative analysis
Measured: baseline, 1 month, 3 months, 6 months follow-up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Aug 2021
- Study start16 Feb 2022
- Primary completionDec 2027 (estimated)
- Study completionDec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Knee OsteoarthritisStudies of the same condition, open and under way.
- More trials run by Istituto Ortopedico RizzoliThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- The study is a double-blinded RCT with possibility ,after 6 months, to cross-over from control arm (saline solution ) to the treatment arm (collagen). After 6 months, patients in the control arm have the possibility to cross-over into the treatment arm, in which case they will be followed for an additional 6 months
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 204 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Istituto Ortopedico Rizzoli
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Alessandro Di Martino, MD, Principal investigator, Istituto Ortopedico Rizzoli
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04998188
- Sponsor's protocol ID
- COLL-OA
- Status last verified
- Jan 2026
- First submitted
- 17 May 2021
- Last updated
- 3 Feb 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Filardo G, Kon E, Longo UG, Madry H, Marchettini P, Marmotti A, Van Assche D, Zanon G, Peretti GM. Non-surgical treatments for the management of early osteoarthritis. Knee Surg Sports Traumatol Arthrosc. 2016 Jun;24(6):1775-85. doi: 10.1007/s00167-016-4089-y. Epub 2016 Apr 4.
PubMed 27043347Volpi P, Zini R, Erschbaumer F, Beggio M, Busilacchi A, Carimati G. Effectiveness of a novel hydrolyzed collagen formulation in treating patients with symptomatic knee osteoarthritis: a multicentric retrospective clinical study. Int Orthop. 2021 Feb;45(2):375-380. doi: 10.1007/s00264-020-04616-8. Epub 2020 May 23.
PubMed 32447428De Luca P, Colombini A, Carimati G, Beggio M, de Girolamo L, Volpi P. Intra-Articular Injection of Hydrolyzed Collagen to Treat Symptoms of Knee Osteoarthritis. A Functional In Vitro Investigation and a Pilot Retrospective Clinical Study. J Clin Med. 2019 Jul 4;8(7):975. doi: 10.3390/jcm8070975.
PubMed 31277508Farr J, Gomoll AH, Yanke AB, Strauss EJ, Mowry KC; ASA Study Group. A Randomized Controlled Single-Blind Study Demonstrating Superiority of Amniotic Suspension Allograft Injection Over Hyaluronic Acid and Saline Control for Modification of Knee Osteoarthritis Symptoms. J Knee Surg. 2019 Nov;32(11):1143-1154. doi: 10.1055/s-0039-1696672. Epub 2019 Sep 18.
PubMed 31533151Furuzawa-Carballeda J, Munoz-Chable OA, Barrios-Payan J, Hernandez-Pando R. Effect of polymerized-type I collagen in knee osteoarthritis. I. In vitro study. Eur J Clin Invest. 2009 Jul;39(7):591-7. doi: 10.1111/j.1365-2362.2009.02154.x.
PubMed 19453649Vucic K, Jelicic Kadic A, Puljak L. Survey of Cochrane protocols found methods for data extraction from figures not mentioned or unclear. J Clin Epidemiol. 2015 Oct;68(10):1161-4. doi: 10.1016/j.jclinepi.2014.11.016. Epub 2014 Dec 18.
PubMed 25577327
Study at a glance
From the registry record, last updated by the sponsor on 3 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Hydrolyzed Collagen Formulation Versus Placebo in the Treatment of Degenerative Knee Cartilage Injuries
- ClinicalTrials.gov ID
- NCT04998188
- Acronym / sponsor ID
- COLL-OA
- Conditions
- Knee Osteoarthritis
- Keywords
- knee, knee osteoarthritis, collagen, collagen injection, osteoarthritis, placebo, Randomized controlled trial, double-blinded
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 204 participants (estimated)
- Lead sponsor
- Istituto Ortopedico RizzoliUniversity, hospital or other
- Study start
- 16 Feb 2022 (actual)
- Primary completion
- Dec 2027 (estimated)
- Study completion
- Dec 2027 (estimated)
- First posted
- 10 Aug 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The aim of the study is to compare the 6 months clinical outcome of the treatment with a single intra-articular collagen injection versus a single placebo (saline solution) infiltration in the infiltrative treatment of knee osteoarthritis. The evaluation will be performed through clinical, subjective and objective assessments.
Detailed description
204 patients affected by knee osteoarthritis will be included in a double-blinded randomized controlled trial. Patients in the experimental group will be treated with a single intra-articular injection of collagen (solution of low molecular weight peptides derived from hydrolyzed collagen) instead patients in the control arm, will be treated with a single intra-articular injection of placebo (saline solution). All patients will be evaluated by clinical examination before the infiltrative procedure and they will follow-up at 1,3,6 months. During the follow-up visits ,will be evaluated the inflammatory status of the knee by thermographic assessment and questionnaires, filled out by patients, will be utilized for clinical evaluations. After 6 months, patients in the control arm (saline solution injection), have the possibility to cross-over into the treatment arm (collagen) in which case they will be followed for an additional 6 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
- Model description
- The study is a double-blinded RCT with possibility ,after 6 months, to cross-over from control arm (saline solution ) to the treatment arm (collagen). After 6 months, patients in the control arm have the possibility to cross-over into the treatment arm, in which case they will be followed for an additional 6 months
| Arm | Type | Receives |
|---|---|---|
| Collagen Injection | Experimental | Procedure: CollagenThis group of patients will be treated with single intra-articular injection of collagen. |
| Placebo (saline solution) | Placebo comparator | Procedure: Placebo (saline solution)This group of patients will be treated with single intra-articular injection of saline solution (placebo). At the 6-month follow-up visit, patients will be informed about the treatment received. Patients of this group can cross-over to the treatment arm after 6 months. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Unilateral involvement;
- Signs and symptoms of degenerative pathology of knee cartilage;
- Radiographic and MRI signs of degenerative pathology of the knee cartilage (Kellgren-Lawrence 1-4 grades);
- Failure, defined as the persistence of symptoms, after at least one course of conservative treatment (pharmacological, physiotherapeutic or infiltrative treatment);
- Ability and consent of patients to actively participate in clinical follow-up;
Key exclusion criteria (13 listed)
- Patients who have undergone intra-articular injections of another substance in the previous 6 months;
- Patients undergoing knee surgery within the previous 12 months;
- Patients with malignant neoplasms;
- Patients with rheumatic diseases;
- Patients with diabetes;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CollagenPatients will be treated with a single injection of collagen (2 ml) in the knee joint affected by osteoarthritis | Procedure or surgery | Collagen Injection |
| Placebo (saline solution)Patients will be treated with a single injections of saline solution (2 ml) in the knee joint affected by osteoarthritis | Procedure or surgery | Placebo (saline solution) |
Primary outcome
KOOS-Pain Score
Time frame: 6 months follow-up
KOOS-Pain Score is referred to a subscale of pain composed by 9 items. The score range considerate is 0-100.The score uses a 5-point Likert scale and each question is assigned a score from 0 to 4, where 0 indicates "no pain" and 4 "severe level of pain"
13 secondary outcomes
IKDC-Subjective Score
Time frame: baseline, 1 month, 3 months, 6 months follow-up
KOOS Score
Time frame: baseline, 1 month, 3 months, 6 months follow-up
WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) score
Time frame: baseline, 1 month, 3 months, 6 and 12 months follow-up
VAS-pain (Visual Analogue Scale)
Time frame: baseline, 1 month, 3 months, 6 months follow-up
EQ-VAS
Time frame: baseline, 1 month, 3 months, 6 months follow-up
EQ-5D (EuroQoL) Current Health Assessment
Time frame: baseline, 1 month, 3 months, 6 months follow-up
TegnerActivity Level Scale
Time frame: baseline, 1 month, 3 months, 6 months follow-up
Patient Acceptable Symptom State (PASS)
Time frame: baseline, 1 month, 3 months, 6 months follow-up
Objective parameters -Range of motion
Time frame: baseline, 1 month, 3 months, 6 months follow-up
Final treatment opinion
Time frame: 6 months follow-up
Ultrasound assessment
Time frame: Baseline
Thermographic evaluation of the inflammatory status of the knee joint
Time frame: baseline, 1 month, 3 months, 6 months follow-up
Objective parameters - Circumferences
Time frame: baseline, 1 month, 3 months, 6 months follow-up
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Feb 2026.
- Background: PubMed 27043347Filardo G, Kon E, Longo UG, Madry H, Marchettini P, Marmotti A, Van Assche D, Zanon G, Peretti GM. Non-surgical treatments for the management of early osteoarthritis. Knee Surg Sports Traumatol Arthrosc. 2016 Jun;24(6):1775-85. doi: 10.1007/s00167-016-4089-y. Epub 2016 Apr 4.
- Background: PubMed 32447428Volpi P, Zini R, Erschbaumer F, Beggio M, Busilacchi A, Carimati G. Effectiveness of a novel hydrolyzed collagen formulation in treating patients with symptomatic knee osteoarthritis: a multicentric retrospective clinical study. Int Orthop. 2021 Feb;45(2):375-380. doi: 10.1007/s00264-020-04616-8. Epub 2020 May 23.
- Background: PubMed 31277508De Luca P, Colombini A, Carimati G, Beggio M, de Girolamo L, Volpi P. Intra-Articular Injection of Hydrolyzed Collagen to Treat Symptoms of Knee Osteoarthritis. A Functional In Vitro Investigation and a Pilot Retrospective Clinical Study. J Clin Med. 2019 Jul 4;8(7):975. doi: 10.3390/jcm8070975.
- Background: PubMed 31533151Farr J, Gomoll AH, Yanke AB, Strauss EJ, Mowry KC; ASA Study Group. A Randomized Controlled Single-Blind Study Demonstrating Superiority of Amniotic Suspension Allograft Injection Over Hyaluronic Acid and Saline Control for Modification of Knee Osteoarthritis Symptoms. J Knee Surg. 2019 Nov;32(11):1143-1154. doi: 10.1055/s-0039-1696672. Epub 2019 Sep 18.
- Background: PubMed 19453649Furuzawa-Carballeda J, Munoz-Chable OA, Barrios-Payan J, Hernandez-Pando R. Effect of polymerized-type I collagen in knee osteoarthritis. I. In vitro study. Eur J Clin Invest. 2009 Jul;39(7):591-7. doi: 10.1111/j.1365-2362.2009.02154.x.
- Background: PubMed 25577327Vucic K, Jelicic Kadic A, Puljak L. Survey of Cochrane protocols found methods for data extraction from figures not mentioned or unclear. J Clin Epidemiol. 2015 Oct;68(10):1161-4. doi: 10.1016/j.jclinepi.2014.11.016. Epub 2014 Dec 18.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Alessandro Di Martino, MD contact
Alessandro Di Martino, MD principal investigator
Istituto Ortopedico Rizzoli
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Collagen in people with Knee Osteoarthritis, run by Istituto Ortopedico Rizzoli at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 3 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Roberta Licciardi, Msc (0516366567, roberta.licciardi@ior.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
KOOS-Pain Score (time frame: 6 months follow-up). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04998188, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Feb 2026.