Polymerized-type I collagen downregulates inflammation and improves clinical outcomes in patients with symptomatic knee osteoarthritis following arthroscopic lavage: a randomized, double-blind, and placebo-controlled clinical trial

Janette Furuzawa-Carballeda, Guadalupe Lima, Luis Llorente, Carlos Nuñez-Álvarez, Blanca H Ruiz-Ordaz, Santiago Echevarría-Zuno, Virgilio Hernández-Cuevas, Janette Furuzawa-Carballeda, Guadalupe Lima, Luis Llorente, Carlos Nuñez-Álvarez, Blanca H Ruiz-Ordaz, Santiago Echevarría-Zuno, Virgilio Hernández-Cuevas

Abstract

Objectives: Polymerized-type I collagen (polymerized collagen) is a downmodulator of inflammation and cartilage regenerator biodrug.

Aim: To evaluate the effect of intraarticular injections of polymerized collagen after arthroscopic lavage on inflammation and clinical improvement in patients with knee osteoarthritis (OA).

Methods: Patients (n = 19) were treated with 6 intraarticular injections of 2 mL of polymerized collagen (n = 10) or 2 mL of placebo (n = 9) during 3 months. Followup was 3 months. The primary endpoints included Lequesne index, pain on a visual analogue scale (VAS), WOMAC, analgesic usage, the number of Tregs and proinflammatory/anti-inflammatory cytokine-expressing peripheral cells. Secondary outcomes were Likert score and drug evaluation. Clinical and immunological improvement was determined if the decrease in pain exceeds 20 mm on a VAS, 20% of clinical outcomes, and inflammatory parameters from baseline. Urinary levels of C-terminal crosslinking telopeptide of collagen type II (CTXII) and erythrocyte sedimentation rate (ESR) were determined.

Results: Polymerized collagen was safe and well tolerated. Patients had a statistically significant improvement (P < 0.05) from baseline versus polymerized collagen and versus placebo at 6 months on Lequesne index, VAS, ESR, Tregs IL-1β, and IL-10 peripheral-expressing cells. Urinary levels of CTXII were decreased 44% in polymerized collagen versus placebo. No differences were found on incidence of adverse events between groups.

Conclusion: Polymerized collagen is safe and effective on downregulation of inflammation in patients with knee OA.

Figures

Figure 1
Figure 1
Primary and secondary measures of efficacy. Clinical evaluation was performed at baseline and every month during the study. The primary endpoints included (a) Lequesne index, (b) patient pain visual analogue scale (VAS), (c) physician pain visual analogue scale (VAS), (d) WOMAC pain subscale, (e) WOMAC stiffness subscale, (f) WOMAC disability subscale, (g) patient's and (h) physician's global assessment of disease activity on a 5-point rating scale, global assessment of change in disease activity at the end of the treatment (Likert score: 0 = very poor; 1 = poor; 2 = fair; 3 = well; 4 = very well), (i) consumption of NSAIDs tablets per month. Arrows depict the month in which the treatment reached a P < 0.05 compared to baseline, in black for placebo and in red for polymerized collagen group. Results represent mean ± SD. P values indicate statistical significant differences between treatment groups.
Figure 2
Figure 2
Percentage of CD14-derived proinflammatory cytokine in OA knee patients. (a) An electronic gate was made for CD4−/CD14+ single positive cells. (b) From the gate a CD4−/CD14+/IL-1β+ cells were determined. (c) Percentage of CD4−/CD14+/IL-1β+ peripheral blood cells was established at baseline, 3, and 6 months. (d) An electronic gate was made for CD4−/CD14+ single positive cells. (e) From the gate d CD4−/CD14+/TNF-α+ cells were determined. (f) Percentage of CD4−/CD14+/TNF-α+ peripheral blood cells was established at baseline, 3, and 6 months. (g) An electronic gate was made for CD4−/CD14+ single positive cells. (h) From the gate f CD4−/CD14+/IL-10+ cells were determined. (i) Percentage of CD4−/CD14+/IL-10+ peripheral blood cells was established at baseline, 3 and 6 months. (j) An electronic gate was made for CD4+/CD14− single positive cells. (k) From the gate j CD4+/CD14−/Foxp3+ cells were determined. (l) Percentage of CD4+/CD14−/Foxp3+ peripheral blood cells was established at baseline, 3, and 6 months. (m) An electronic gate was made for CD8+/CD28− single positive cells. (n) From the gate m CD8+/CD28−/Foxp3+ cells were determined. (o) Percentage of CD8+/CD28−/Foxp3+ peripheral blood cells was established at baseline, 3, and 6 months. The software employed was CellQuest (BD Biosciences). A total of 50,000 events were recorded for each sample. Results are expressed as mean ± SE. *P < 0.05.
Figure 3
Figure 3
Total cytokine- and Foxp3-expressing peripheral cells in patients with symptomatic knee OA under Polymerized-type I collagen or placebo at baseline, 3, and 6 months.

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