Hydrolyzed Collagen Formulation vs Placebo in Knee Osteoarthritis

Knee Osteoarthritis Clinical Trial

Official title:

Hydrolyzed Collagen Formulation Versus Placebo in the Treatment of Degenerative Knee Cartilage Injuries

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04998188
• Other study ID #: COLL-OA
• Status: Recruiting
• Phase: N/A
• Start date: February 16, 2022
• Est. completion date: December 2025

Study information

• Verified date: September 2023
• Source: Istituto Ortopedico Rizzoli
• Contact: Roberta Licciardi, Msc
• Phone: 0516366567
• Email: roberta.licciardi[@]ior.it
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. The evaluation will be performed through clinical, subjective and objective assessments.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 204
• Est. completion date: December 2025
• Est. primary completion date: August 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Unilateral involvement;

2. Signs and symptoms of degenerative pathology of knee cartilage;

3. Radiographic and MRI signs of degenerative pathology of the knee cartilage (Kellgren-Lawrence 1-4 grades);

4. Failure, defined as the persistence of symptoms, after at least one course of conservative treatment (pharmacological, physiotherapeutic or infiltrative treatment);

5. Ability and consent of patients to actively participate in clinical follow-up;

Exclusion Criteria:

1. Patients who have undergone intra-articular injections of another substance in the previous 6 months;

2. Patients undergoing knee surgery within the previous 12 months;

3. Patients with malignant neoplasms;

4. Patients with rheumatic diseases;

5. Patients with diabetes;

6. Patients with hematologic diseases (coagulopathies);

7. Patients on anticoagulant therapy;

8. Patients with metabolic disorders of the thyroid gland;

9. Patients abusing alcoholic beverages, drugs or medications;

10. Body Mass Index > 35;

11. Pregnant or lactating women.

12. Patients with established hypersensitivity to bovine collagen or vitamin C.

13. Patients with joint or peri-articular infections, emarto, erythema, or psoriatic patches in the knee joint area

Related Conditions & MeSH terms

• Knee Osteoarthritis
• Osteoarthritis
• Osteoarthritis, Knee

Intervention

Procedure:
• Collagen
Patients will be treated with a single injection of collagen (2 ml) in the knee joint affected by osteoarthritis
• Placebo (saline solution)
Patients will be treated with a single injections of saline solution (2 ml) in the knee joint affected by osteoarthritis

Locations

Country	Name	City	State
Italy	Istituto Ortopedico Rizzoli	Bologna

Sponsors (1)

Lead Sponsor	Collaborator
Istituto Ortopedico Rizzoli

Country where clinical trial is conducted

Italy, 

References & Publications (6)

De 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. — View Citation

Farr 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. Erratum In: J Knee Surg. 2019 Nov;32(11):e2. — View Citation

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. — View Citation

Furuzawa-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. — View Citation

Volpi 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. — View Citation

Vucic 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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"	6 months follow-up
Secondary	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	baseline, 1 month, 3 months, 6 months follow-up
Secondary	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	baseline, 1 month, 3 months, 6 months follow-up
Secondary	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.	baseline, 1 month, 3 months, 6 and 12 months follow-up
Secondary	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".	baseline, 1 month, 3 months, 6 months follow-up
Secondary	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).	baseline, 1 month, 3 months, 6 months follow-up
Secondary	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.	baseline, 1 month, 3 months, 6 months follow-up
Secondary	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	baseline, 1 month, 3 months, 6 months follow-up
Secondary	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".	baseline, 1 month, 3 months, 6 months follow-up
Secondary	Objective parameters -Range of motion	Evaluation of the Range of Motion for comparative analysis.	baseline, 1 month, 3 months, 6 months follow-up
Secondary	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".	6 months follow-up
Secondary	Ultrasound assessment	This examination is useful to do an initial assessment of possible meniscal extrusion in the interested knee joint.	Baseline
Secondary	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.	baseline, 1 month, 3 months, 6 months follow-up
Secondary	Objective parameters - Circumferences	Bilateral trans- and supra- patellar circumferences measurement for comparative analysis	baseline, 1 month, 3 months, 6 months follow-up