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

Emilio López-Vidriero, Ramón Olivé-Vilas, David López-Capapé, Luisa Varela-Sende, Rosa López-Vidriero, Luís Til-Pérez, Emilio López-Vidriero, Ramón Olivé-Vilas, David López-Capapé, Luisa Varela-Sende, Rosa López-Vidriero, Luís Til-Pérez

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 (ClinicalTrials.gov identifier).

Keywords: anterior cruciate ligament tears; chondroitin sulfate; collagen; dietary supplementations; hyaluronic acid; platelet-rich plasma; vitamin C.

Conflict of interest statement

One or more of the authors has declared the following potential conflict of interest or source of funding: OPKO Health Spain SL provided financial support for the conduct of the research. E.L.-V. and D.L.-C. have received financial support for attending symposia as well as research support from OPKO. R.O.-V. has received financial support for attending symposia from OPKO. L.V.-S. is a member of the Clinical Research Department of OPKO. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto.

Figures

Figure 1.
Figure 1.
Flow diagram of the patients included in the study. MRI, magnetic resonance imaging.
Figure 2.
Figure 2.
Efficacy assessments during the follow-up in the control and supplemented groups. (A) International Knee Documentation Committee score. (B) Visual analog scale pain score. *P < .05, between-group comparison.
Figure 3.
Figure 3.
Analgesic consumption during the follow-up in the control and supplemented groups.
Figure 4.
Figure 4.
Number of rehabilitation sessions needed for recovery in the control and supplemented groups. ***P < .001, between-group differences.
Figure 5.
Figure 5.
Perception of efficacy and tolerability in the control and supplemented groups throughout all follow-up visits (V2-V5). Perception of efficacy by (A) physicians and (B) patients. Perception of tolerability by (C) physicians and (D) patients. *P < .05, between-group differences.

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