Clinical trial NCT04998188: Hydrolyzed Collagen Formulation vs Placebo in Knee Osteoarthritis
Official title: Hydrolyzed Collagen Formulation Versus Placebo in the Treatment of Degenerative Knee Cartilage Injuries
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Knee Osteoarthritis
Keywords: knee
knee osteoarthritis
collagen
collagen injection
osteoarthritis
placebo
Randomized controlled trial
double-blinded
Lead sponsor: Istituto Ortopedico Rizzoli
Sponsor class: OTHER
First posted: 2021-08-10
Enrollment: 204
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention 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
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: KOOS-Pain Score
timeFrame: 6 months follow-up
Secondary outcomes:
measure: IKDC-Subjective Score
timeFrame: baseline, 1 month, 3 months, 6 months follow-up
measure: KOOS Score
timeFrame: baseline, 1 month, 3 months, 6 months follow-up
measure: WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) score
timeFrame: baseline, 1 month, 3 months, 6 and 12 months follow-up
measure: VAS-pain (Visual Analogue Scale)
timeFrame: baseline, 1 month, 3 months, 6 months follow-up
measure: EQ-VAS
timeFrame: baseline, 1 month, 3 months, 6 months follow-up
measure: EQ-5D (EuroQoL) Current Health Assessment
timeFrame: baseline, 1 month, 3 months, 6 months follow-up
measure: TegnerActivity Level Scale
timeFrame: baseline, 1 month, 3 months, 6 months follow-up
measure: Patient Acceptable Symptom State (PASS)
timeFrame: baseline, 1 month, 3 months, 6 months follow-up
measure: Objective parameters -Range of motion
timeFrame: baseline, 1 month, 3 months, 6 months follow-up
measure: Final treatment opinion
timeFrame: 6 months follow-up
measure: Ultrasound assessment
timeFrame: Baseline
measure: Thermographic evaluation of the inflammatory status of the knee joint
timeFrame: baseline, 1 month, 3 months, 6 months follow-up
measure: Objective parameters - Circumferences
timeFrame: baseline, 1 month, 3 months, 6 months follow-up
Other outcomes:
Locations:
city: Bologna
country: Italy
facility: Istituto Ortopedico Rizzoli
Study officials:
affiliation: Istituto Ortopedico Rizzoli
name: Alessandro Di Martino, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
citation: 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.
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.
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.
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.