Hydrolyzed Collagen Formulation vs Placebo in Knee Osteoarthritis

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Knee Osteoarthritis

Intervention / Treatment
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* Procedure: Collagen
* Procedure: Placebo (saline solution)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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; Exclusion Criteria: 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); 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional 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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Collagen Injection<br>This group of patients will be treated with single intra-articular injection of collagen. | Procedure: Collagen<br>* Patients will be treated with a single injection of collagen (2 ml) in the knee joint affected by osteoarthritis<br>|
| Placebo Comparator: Placebo (saline solution)<br>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. | Procedure: Placebo (saline solution)<br>* Patients will be treated with a single injections of saline solution (2 ml) in the knee joint affected by osteoarthritis<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| Objective parameters -Range of motion | Evaluation of the Range of Motion for comparative analysis. | 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. | 6 months follow-up | 
| Ultrasound assessment | This examination is useful to do an initial assessment of possible meniscal extrusion in the interested knee joint. | 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. | baseline, 1 month, 3 months, 6 months follow-up | 
| Objective parameters - Circumferences | Bilateral trans- and supra- patellar circumferences measurement for comparative analysis | baseline, 1 month, 3 months, 6 months follow-up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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knee, knee osteoarthritis, collagen injection, osteoarthritis, placebo, Randomized controlled trial, double-blinded, collagen