Efficacy and Tolerability of Progen, a Nutritional Supplement Based on Innovative Plasma Proteins, in ACL Reconstruction: A Multicenter Randomized Controlled Trial

Abstract

Background: New biologic strategies are arising to enhance healing and improve the clinical outcome of anterior cruciate ligament (ACL) reconstruction. Purpose: To evaluate the efficacy of a new oral nutritional supplement (Progen) that contains hydrolyzed collagen peptides and plasma proteins, a hyaluronic acid–chondroitin sulfate complex, and vitamin C. Study Design: Randomized controlled trial; Level of evidence, 2. Methods: The study included patients who underwent ACL reconstruction with hamstring autografts using the same fixation method. All patients received the same analgesia and physical therapy (PT) protocol and were randomized to receive either the nutritional supplement (supplemented group) or no additional therapy (control group). Patients were followed up at days 7, 30, 60, and 90. Pain was assessed by use of a visual analog scale (VAS) and by analgesic consumption. Clinical outcome was assessed via International Knee Documentation Committee (IKDC) score and the number of PT sessions. Perceived efficacy and tolerability were rated on a 5-point Likert scale. Graft maturation was assessed by a blinded musculoskeletal radiologist using magnetic resonance imaging. The number of adverse events (AEs) was recorded. Results: The intention-to-treat analysis included 72 patients, 36 allocated to the supplemented group and 36 to the control group, with no significant differences regarding demographic and preoperative characteristics. Both groups showed significant improvement in pain and function (measured by VAS and IKDC scores) during the 90-day follow-up period ( P < .001 for both), without significant differences between groups. The supplemented group had fewer patients that needed analgesics (8.5% vs 50.0%; P < .05) and attended fewer PT sessions (38.0 vs 48.4 sessions; P < .001) at 90 days and had a higher IKDC score at 60 days (62.5 vs 55.5; P = .029) compared with the control group. Patient- and physician-perceived efficacy was considered significantly higher in the supplemented group at 60 and 90 days ( P < .05). Perceived tolerability of the overall intervention was better in the supplemented group at 30, 60, and 90 days ( P < .05). Graft maturation showed more advanced degrees (grades 3 and 4) in the supplemented group at 90 days (61.8% vs 38.2%; P < .01). No intolerance or AEs associated with the nutritional supplement treatment were reported. Conclusion: The combination of the nutritional supplement and PT after ACL reconstruction improved pain, clinical outcome, and graft maturation. Nutritional supplementation showed higher efficacy during the second month of recovery, without causing AEs. Registration: NCT03355651 ( ...

Influence of platelet-rich plasma (PRP) analogues on healing and clinical outcomes following anterior cruciate ligament (ACL) reconstructive surgery: a systematic review

“…Whilst the results of Lopez-Vidriero et al [12] and Seijas et al [28] are in agreement, it should be highlighted that the comparison of these results proves difficult due to different forms of PRP being used; Lopez-Vidriero et al [12] provided oral supplementation of PRP, Seijas et al [28] using simple injectable PRP and Valenti Nin et al [22] using PDGF gel. On the other hand, the use of different preparations of PRP may help in determining which form is most suited in improving ligamentization rates.…”

“…No significant difference was found beyond 6 months. Seven studies [11,12,[15][16][17][18]22] evaluated knee function, two of which found PRP to improve overall knee function [11,12]. No significant difference was found beyond 12 months.…”

“…Five studies recorded platelet levels within PRP; de Almeida et al [ 15 ] (1,185,166/mm 3 ± 404,472/mm 3 ), Vogrin et al [ 14 ] (average: 962 G/l range: 552–1326), Valenti Nin et al [ 22 ] (average: 837 × 10 3 /mm 3 ), Walters et al [ 18 ] (2–3 × above baseline) and M. Mahdi and Halwas Jhale [ 16 ] (5.0–7.0 platelets per preparation). Lopez-Vidriero et al [ 12 ] stated the contents of the supplement sachets; 2500 mg of chondroitin sulphate, 300 mg of porcine PRP, 50 mg hyaluronic acid and 40 mg Vitamin C. The remaining studies did not report platelet levels within PRP.…”

“…The methods used were peritendon and fat pad sutures, suturing PRP into the internal aspect of graft and no use of arthroscopic fluid. Only Lopez-Vidriero et al [ 12 ] trialled multiple applications of intervention, with oral supplementation provided once daily for a 90-day period (Table 3 ).…”

“…There were a number of studies displaying deficits in aspects of their methodology. Four studies: Cerevellin et al [ 11 ], Lopez-Vidriero et al [ 12 ], Mirzatolooei et al [ 13 ] and Vogrin et al [ 14 ] did not blind all participants and study personnel to treatment. A further three studies; de Almeida et al [ 15 ], Mahdi and Halwas Jhale [ 16 ] and Vadala et al [ 17 ] did not state whether all study personnel and participants were blinded.…”