1.
Clinical effects of the three CFTR potentiator treatments curcumin, genistein and ivacaftor in patients with the CFTR-S1251N gating mutation.
Berkers, G, van der Meer, R, van Mourik, P, Vonk, AM, Kruisselbrink, E, Suen, SW, Heijerman, HG, Majoor, CJ, Koppelman, GH, Roukema, J, et al
Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society. 2020;(6):955-961
Abstract
BACKGROUND The natural food supplements curcumin and genistein, and the drug ivacaftor were found effective as CFTR potentiators in the organoids of individuals carrying a S1251N gating mutation, possibly in a synergistic fashion. Based on these in vitro findings, we evaluated the clinical efficacy of a treatment with curcumin, genistein and ivacaftor, in different combinations. METHODS In three multi-center trials people with CF carrying the S1251N mutation were treated for 8 weeks with curcumin+genistein, ivacaftor and ivacaftor+genistein. We evaluated change in lung function, sweat chloride concentration, CFQ-r, BMI and fecal elastase to determine the clinical effect. We evaluated the pharmacokinetic properties of the compounds by evaluating the concentration in plasma collected after treatment and the effect of the same plasma on the intestinal organoids. RESULTS A clear clinical effect of treatment with ivacaftor was observed, evidenced by a significant improvement in clinical parameters. In contrast we observed no clear clinical effect of curcumin and/or genistein, except for a small but significant reduction in sweat chloride and airway resistance. Plasma concentrations of the food supplements were low, as was the response of the organoids to this plasma. CONCLUSIONS We observed a clear clinical effect of treatment with ivacaftor, which is in line with the high responsiveness of the intestinal organoids to this drug. No clear clinical effect was observed of the treatment with curcumin and/or genistein, the low plasma concentration of these compounds emphasizes that pharmacokinetic properties of a compound have to be considered when in vitro experiments are performed.
2.
The efficacy and safety of a combination of glucosamine hydrochloride, chondroitin sulfate and bio-curcumin with exercise in the treatment of knee osteoarthritis: a randomized, double-blind, placebo-controlled study.
Sterzi, S, Giordani, L, Morrone, M, Lena, E, Magrone, G, Scarpini, C, Milighetti, S, Pellicciari, L, Bravi, M, Panni, I, et al
European journal of physical and rehabilitation medicine. 2016;(3):321-30
Abstract
BACKGROUND Knee osteoarthritis (OA) conservative treatment aims to delay cartilage degeneration; chondroprotective agents are a valid approach in this sense. A commercially available dietary supplement, CartiJoint Forte, containing glucosamine hydrochloride (GH), chondroitin sulfate (CS) and Bio-Curcumin BCM-95®, was used in this trial. AIM: The aim of this study was to assess efficacy and safety of CartiJoint Forte combined with physical therapy in treating subjects with knee OA. DESIGN A multicenter, prospective, randomized, double blind, placebo-controlled clinical trial. SETTING Outpatients referred to the Rehabilitation Departments of two University Hospitals. POPULATION Fifty-three patients were randomly assigned to an experimental group (N=26) or a control group (N.=27). Experimental subjects received two tablets of CartiJoint Forte each day for 8 weeks, while those in the control group were provided with a placebo. Three subjects dropped out during the course of the study. METHODS The two groups both received 20 sessions of physical therapy during the course of the trial. Primary outcome was pain intensity, measured both at motion and at rest, using the Visual Analogue Scale (VAS). A secondary outcome was an assessment of knee function by Western Ontario and McMaster Universities Arthritis Index and Lequesne Index, knee ROM, and two inflammation markers (C-reactive protein and erythrocyte sedimentation rate). Each assessment was carried out at baseline (T0), at 8 weeks (T1) and at 12 weeks (T2). RESULTS VAS at rest was found to be reduced between T0 and T1, as well as between T0 and T2 (F=13.712; P=0.0001), with no differences between groups (F=1.724; P=0.191). VAS at motion revealed a significant "group × time-check" interaction (F=2.491; P=0.032), with increasing effect of time on VAS reduction (F=17.748; P=0.0001). This was most pronounced in the experimental group at 8 weeks (F=3.437; P=0.045). The Lequesne Index showed reductions at T1 and T2 compared to T0 (F=9.535; P=0.0001), along with group effect, since the experimental group presented a lower score at T2 (F=7.091; P=0.009). No significant changes were found in the knee ROM and inflammation markers. CONCLUSION CartiJoint Forte, added to physical therapy, may ameliorate pain and help to improve algofunctional score in knee OA patients. CLINICAL REHABILITATION IMPACT Treatment of knee OA with curcuminoids plus glycosaminoglycans, added to physical therapy, improves VAS at motion and Lequesne Index scores.