The short-term effect of glucosamine-sulfate, nonanimal chondroitin-sulfate, and S-adenosylmethionine combination on ultrasonography findings, inflammation, pain, and functionality in patients with knee osteoarthritis: A pilot, double-blind, randomized, placebo-controlled clinical trial

Abstract

Objectives: This study aimed to investigate the efficacy of glucosamine-sulfate (GS), nonanimal chondroitin-sulfate (naCS), and S-adenosylmethionine (SAMe) combination on ultrasound findings, inflammation, pain, and functionality in knee osteoarthritis.

Patients and methods: In the prospective, randomized, double-blind, placebo-controlled pilot study conducted between August 2019 and November 2019, 120 participants (28 males, 92 females; mean age: 66.4±7.9 years; range, 42.4 to 74.5 years) were randomized at a 1:1:1 ratio to the placebo group, the first experimental group (a combination of GS, naCS, and SAMe was administered to the experimental groups. The first experimental group received 375 mg of GS, 300 mg of naCS, and 100 mg of SAMe, whereas the second experimental group received 750 mg of GS, 600 mg of naCS, and 200 mg of SAMe). Laboratory (erythrocyte sedimentation rate, C-reactive protein, tumor necrosis factor alpha, interleukin [IL]-1β, IL-6, IL-17), clinical (Visual Analog Scale [VAS], short form health survey [SF-36], the Western Ontario and McMaster Universities Arthritis Index [WOMAC], and the Tegner Lysholm Knee Scoring Scale [TLKS]), and musculoskeletal ultrasound (MSUS) assessments were performed at baseline and after three and six months.

Results: A minor increase was observed in the second experimental group after six months using ultrasonography to evaluate articular cartilage thickness (p<0.05). The investigational product's superiority in reducing osteoarthritis ultrasonographic findings was not proven. A moderately negative association was found between cartilage thickness and VAS scores at baseline (ρ=-0.36, p<0.01), while the presence of massive osteophytes on MSUS showed a low to moderate association with all clinical outcomes. There was no difference in the delta changes between groups for the VAS, TLKS, WOMAC, and SF-36. The only serum inflammatory marker outside the reference range was IL-1β, but no significant changes were observed after six months.

Conclusion: According to the results of our investigation, treatment for knee osteoarthritis should be evaluated using more objective outcomes. The most important conclusion of our study is that IP may result in a slight increase in articular cartilage thickness, which was associated with a decrease in pain intensity at baseline. Clarification of the potential influence of this combination on radiographic progression and laboratory markers of inflammation requires further exploration.

†These authors made equal contributions.

Citation: Veličković Z, Dolijanović SP, Stojanović N, Janjić S, Kovačević L, Soldatović I, et al. The short-term effect of glucosaminesulfate, nonanimal chondroitin-sulfate, and S-adenosylmethionine combination on ultrasonography findings, inflammation, pain, and functionality in patients with knee osteoarthritis: A pilot, double-blind, randomized, placebo-controlled clinical trial. ArchRheumatol2023;38(4):521-541.doi:10.46497/ ArchRheumatol.2023.9994.

The study protocol was approved by the Institute of Rheumatology (Belgrade, Serbia) Ethics Committee (date: 03.07.2019, no: 29/1-21). The study was conducted in accordance with the principles of the Declaration of Helsinki.

Each participant who took part in the study signed a consent to publish form. They receive informations about the security protocol for protecting personal data.

Idea/concept: G.R., Z.V.; Design: G.R., Z.V., S.M.; Control/supervision: G.R.; Data collection and/or processing: Z.V., N.S., S.J., L.K., I.S., B.S., T.Ž.R., V.B.; Analysis and/or interpretation: G.R., Z.V., S.P.D., I.S.; Literature review: G.R., Z.V., S.P.D.; Writing the article: G.R., Z.V., S.P.D., N.S., S.J., L.K., I.S.; Critical review: G.R., Z.V., S.P.D.; References and Funding: G. R., Z.V., S.M.; Materials: S.M.

Company supplied study site with study drug and placebo for all patients. This is the first random-ized trial to evaluate efficacy of CS+naGS+SAMe. Company didn’t interfere with study results and they agreed to accept all conclusions about efficacy of their product.
Dr Saša Janjić received fee as investigators for patient reqruitment and patients’ study visits. Dr Ljiljana Kovačević received fee for laboratory analysis. Dr Ivan Soldatović received fee for protocol design and statistical analysis. Dr Zoran Veličković, Dr Slavica Pavlov Dolijanović, Dr Nikola Stojanović and Dr Goran Radu-nović declare no conflict of interest.

Study and investigational products were sponsored by the pharmaceutical company Abela pharm (Belgrade, Serbia).

The authors confirm that the data supporting the findings of this study are available within the article and/or its supplementary materials. Raw data were generated at Institute of Rheumatology. Derived data supporting the findings of this study are available from the corresponding author (G.R., Z.V.) on request.