Rubus idaeus extract improves symptoms in knee osteoarthritis patients: results from a phase II double-blind randomized controlled trial

Yves Henrotin, Romain Le Cozannet, Pascale Fança-Berthon, Romain Truillet, Martine Cohen-Solhal, Gillian DunnGalvin, Jean-Marie Grouin, Andrea Doolan, Yves Henrotin, Romain Le Cozannet, Pascale Fança-Berthon, Romain Truillet, Martine Cohen-Solhal, Gillian DunnGalvin, Jean-Marie Grouin, Andrea Doolan

Abstract

Background: Osteoarthritis (OA) is the most frequent cause of disability in elderly people. In daily practice, the main objective of the physician is to reduce patient symptoms using treatments without adverse effects. However, the most prescribed treatment to manage OA symptoms remains nonsteroidal anti-inflammatory drugs which are associated with severe adverse effects. Therefore, we need a safe alternative to managing OA. One candidate is Rubus idaeus leaf extracts known to inhibit inflammatory responses.

Objective: This study aimed to evaluate the effects of a 12-weeks intervention with an ethanolic extract from Rubus idaeus leaf on symptoms of knee osteoarthritis.

Method: The study was a randomized, double-blind, placebo-controlled, monocentric trial of 198 participants with femorotibial osteoarthritis. Participants were randomized equally to receive one daily during 3 months either 1 capsule of Rubus idaeus leaf extract 400 mg, 1 capsule of Rubus idaeus leaf extract 200 mg, or 1 capsule of placebo. The participants were assessed at baseline and after one and three months of treatment. The primary endpoint was an absolute change of the Western Ontario McMaster osteoarthritis index (WOMAC) pain subscale. The secondary endpoints were WOMAC global score, stiffness and function sub-scales, knee pain VAS score at walking, the Short Form (SF)-36, the Short Physical Performance Battery (SPPB), the 20-m walk test, and the International Physical Activity Questionnaire (IPAQ) and Outcome Measures in Rheumatology Clinical Trials and Osteoarthritis Research Society International (OMERACT-OARSI) responders rate. Statistical analyses were conducted on the intent-to-treat (ITT) population.

Results: In the Intention-to-treat population, WOMAC pain was not significantly modified by Rubus idaeus leaf extract compared to placebo. In contrast, Rubus idaeus leaf extract 400 mg after 12 weeks of treatment significantly reduced pain measured by the VAS. The mean pain decrease induced by Rubus ideaus leaf extract was over -7 mm which is clinically relevant and reached a clinically statistical difference compared to placebo with the highest dose. Rubus Ideaus was not significantly more efficient than the placebo on WOMAC global score, stiffness, and physical function subscores, IPAQ, SF-36, walking distance in treadmill test, SPPB, and evaluation of associated treatments needed to manage OA.

Conclusion: Rubus idaeus leaf extract was well tolerated and effective to relieve pain in a patient with knee osteoarthritis.

Trial registration: NCT03703024 (11/10/2018).

Keywords: Clinical trial; Knee; Osteoarthritis; Pain; Rubus idaeus.

Conflict of interest statement

YH received consulting fees from Naturex and is the founder and president of Artialis SA. RT from Atlanstats and JMG supported statistical analysis. RLC and PB are employees of Naturex. GDG and AD are employees of Atlantia. MCS has no disclosed conflicts of interest.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
Flow diagram of RUBUS study
Fig. 2
Fig. 2
Time evolution of the VAS pain score in ITT population. * = significant effect of RIE 400 mg compared to placebo
Fig. 3
Fig. 3
Time evolution of VAS pain in the participant of the ITT population with a Body Mass Index (BMI) > to 25. * = significant effect of RIE compared to placebo
Fig. 4
Fig. 4
Percentage of participants of the ITT population responding to treatment according to OMERACT-OARSI criteria. * = significant effect of RIE compared to placebo

References

    1. FDA . Administration. Osteoarthritis: structural endpoints for the development of drugs, devices, and biological products for treatment guidance for industry- Services USDoHaH. 2018.
    1. Bannuru RR, Osani MC, Vaysbrot EE, Arden NK, Bennell K, Bierma-Zeinstra SMA, Kraus VB, Lohmander LS, Abbott JH, Bhandari M, Blanco FJ, Espinosa R, Haugen IK, Lin J, Mandl LA, Moilanen E, Nakamura N, Snyder-Mackler L, Trojian T, Underwood M, McAlindon TE. OARSI guidelines for the non-surgical management of knee, hip, and polyarticular osteoarthritis. Osteoarthritis Cartilage. 2019;27(11):1578–1589. doi: 10.1016/j.joca.2019.06.011.
    1. Liu X, Machado GC, Eyles JP, Ravi V, Hunter DJ. Dietary supplements for treating osteoarthritis: a systematic review and meta-analysis. Br J Sports Med. 2018;52(3):167–175. doi: 10.1136/bjsports-2016-097333.
    1. Bourmaud M, Zarka M, Le Cozannet R, Fança-Berthon P, Hay E, Cohen-Solal M. Effect of Rubus idaeus Extracts in Murine Chondrocytes and Explants. Biomolecules. 2021;11(2):245. 10.3390/biom11020245.
    1. Kim HR, Jeong DH, Kim S, Lee SW, Sin HS, Yu KY, Jeong SI, Kim SY. Fermentation of Blackberry with L. plantarum JBMI F5 Enhance the Protection Effect on UVB-Mediated Photoaging in Human Foreskin Fibroblast and Hairless Mice through Regulation of MAPK/NF-κB Signaling. Nutrients. 2019;11(10):PII:E2429. doi: 10.3390/nu11102429.
    1. Jean-Gilles D, Li L, Ma H, Yuan T, Chichester CO, 3rd, Seeram NP. Anti-inflammatory effects of polyphenolic-enriched red raspberry extract in an antigen-induced arthritis rat model. J Agric Food Chem. 2012;60(23):5755–5762. doi: 10.1021/jf203456w.
    1. Lecozannet R, Fanca-Berthon P, Falcao L, Tenon M, Bily A, Roller M, Feuillere N, Birtic, Simona. US2020222486A1.
    1. Belcaro G, Cesarone MR, Dugall M, Pellegrini L, Ledda A, Grossi MG, Togni S, Appendino G. Efficacy and safety of Meriva®, a curcumin-phosphatidylcholine complex, during extended administration in osteoarthritis patients. Altern Med Rev. 2010;15(4):337–344.
    1. Farid R, Rezaieyazdi Z, Mirfeizi Z, Hatef MR, Mirheidari M, Mansouri H, Esmaelli H, Bentley G, Lu Y, Foo Y, Watson RR. Oral intake of purple passion fruit peel extract reduces pain and stiffness and improves physical function in adult patients with knee osteoarthritis. Nutr Res. 2010;30(9):601–606. doi: 10.1016/j.nutres.2010.08.010.
    1. Bannuru RR, Schmid CH, Kent DM, Vaysbrot EE, Wong JB, McAlindon TE. Comparative effectiveness of pharmacologic interventions for knee osteoarthritis: a systematic review and network meta-analysis. Ann Intern Med. 2015;162(1):46–54. doi: 10.7326/M14-1231.
    1. Henrotin Y, Malaise M, Wittoek R, de Vlam K, Brasseur JP, Luyten FP, Jiangang Q, Van den Berghe M, Uhoda R, Bentin J, De Vroey T, Erpicum L, Donneau AF, Dierckxsens Y. Bio-optimized Curcuma longa extract is efficient on knee osteoarthritis pain: a double-blind multicenter randomized placebo-controlled three-arm study. Arthritis Res Ther. 2019;21(1):179–190. doi: 10.1186/s13075-019-1960-5.
    1. Ludwig IA, Mena P, Calani L, Borges G, Pereira-Caro G, Bresciani L, Del Rio D, Lean ME, Crozier A. New insights into the bioavailability of red raspberry anthocyanins and ellagitannins. Free Radic Biol Med. 2015;89:758–769. doi: 10.1016/j.freeradbiomed.2015.10.400.

Source: PubMed

스폰서 및 공동 작업자

건강 상태

약물 개입

3
구독하다