Efficacy and safety of nitazoxanide and escitalopram as adjuvant therapies in patients with rheumatoid arthritis: a randomized controlled study Tarek M. Mostafa, Abeer A. El-Sayed, Abdel Moaty A. Afifi, Dalia R. El-Afify European Journal of Clinical Pharmacology, 2025 Objective This research aimed at evaluating the effectiveness and safety of nitazoxanide and escitalopram as adjuvant therapies in patients with rheumatoid arthritis (RA). Methods In this randomized controlled parallel study, 90 patients with active RA were randomized into three groups; group 1 (control group; n = 30) which received traditional therapy, group 2 (Nitazoxanide group; n = 30) which received traditional therapy plus 1 gm/day oral nitazoxanide, and group 3 (Escitalopram group; n = 30) which received traditional therapy plus 10 mg/day oral escitalopram for three months. At baseline and 3 months after treatment, clinical and functional assessments were done through the 28-joint count disease activity score using C-reactive protein (DAS28-CRP), the health assessment questionnaire-disability index (HAQ-DI), and the patient’s global assessment (PGA). Also, serum levels of high-sensitivity C-reactive protein (hs-CRP), signal transducer and activator of transcription-3 (STAT-3), Janus kinase-2 (JAK-2), toll-like receptors 4 (TLR-4), interleukin-1 beta (IL-1β), and malondialdehyde (MDA) were assessed. Data were analyzed using paired t-test and one-way analysis of variance, followed by Tukey’s HDS test. Results Three months after treatment and as compared to the control group, the nitazoxanide group showed a significant decline in PGA (P = 0.042), and serum levels of STAT-3 (P < 0.001), JAK-2 (P < 0.001), TLR-4 (P < 0.001), and IL-1β (P < 0.001). On the other hand, the escitalopram group produced a significant decrease in DAS28-CRP score (P = 0.029), HAQ-DI score (P = 0.001), and serum levels of JAK-2 (P = 0.001), TLR-4 (P < 0.001), IL-1β (P < 0.001), and MDA (P < 0.001). As compared to nitazoxanide group, the escitalopram group produced a significant decline in fatigue score (P < 0.001) and serum levels of both IL-1β (P = 0.023) and MDA (P < 0.001). Both medications were safe; however, chromaturia was the only significant nitazoxanide-related adverse effect. Conclusion Nitazoxanide and escitalopram could serve as potential adjuvant therapies for patients with RA based on their effectiveness and safety data.
Randomized controlled trial evaluating synbiotic supplementation as an adjuvant therapy in the treatment of Parkinson’s disease Mohamed E. Ramadan, Tarek M. Mostafa, Azza A. Ghali, Dalia R. El-Afify Inflammopharmacology, 2025 Background and aim Neuroinflammatory mechanisms have been closely related to the microbiota-gut-brain axis and could lead to degeneration of dopaminergic neurons with subsequent development and progression of Parkinson’s disease (PD). Targeting this pathway for the treatment of PD has sparked a lot of interest. Hence, this study investigates the therapeutic potential of a synbiotic supplement, in conjunction with l-dopa for the management of PD. Methods This randomized controlled trial enrolled 66 Parkinson's disease patients, who were randomly assigned to two groups: a control group (n = 33) receiving standard l-dopa/carbidopa (100/25 mg) therapy three times daily for three months, and a synbiotic group (n = 33) receiving the same l-dopa/carbidopa regimen with two sachets of the synbiotic supplement daily for three months. The outcome measures included assessment of Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) and serum levels of tumor necrosis factor-alpha (TNF-α), malondialdehyde (MDA), brain-derived neurotrophic factor (BDNF), and α-synuclein (α-Syn). Blood samples were collected from all patients for biomarker analysis in serum. Results Three months after intervention, the synbiotic group demonstrated significantly greater improvement in motor and non-motor symptoms compared to the control group evidenced by the change in the scores of each part of the MDS-UPDRS. Concurrently, the synbiotic group exhibited significantly lower serum levels of pro-inflammatory marker TNF-α and oxidative stress marker MDA, and significantly higher levels of the neuroprotective factor BDNF. Conclusion Supplementing with synbiotics exhibits promising neuroprotective and therapeutic effects in the treatment of Parkinson’s disease patients. Clinicaltrials.gov registration number NCT05576818. Retrospectively registered in October 2022.
A randomized clinical study to evaluate the possible antifibrotic effect of zinc sulfate in chronic HCV patient receiving direct-acting anti-viral therapy Sahar M. El-Haggar, Dina S. Attalla, Mostafa Elhelbawy, Dalia R. El-Afify Inflammopharmacology, 2025 Objective This study aimed to assess the potential antifibrotic impact of zinc sulfate in chronic Hepatitis C Virus (HCV) patients receiving direct-acting antiviral therapy. Methods This randomized controlled study included 50 chronic HCV-infected patients with fibrosis stage (F1 & F2). Participants were randomly assigned to two groups: Group 1 (Control group, n = 25) received standard direct-acting antiviral therapy for 3 months, while Group 2 (Zinc group, n = 25) received 50 mg/day of zinc sulfate in addition to the standard direct-acting antiviral therapy for the same duration. Baseline and 3-month post-intervention assessments included evaluating serum levels of hyaluronic acid, transforming growth factor beta-1, and fibronectin. Furthermore, indices of liver fibrosis, such as the Fibrosis Index based on the 4 factors (FIB-4) and the Aspartate Transaminase-to-Platelet-Ratio Index (APRI), were calculated during these assessments. Results At baseline, the two studied groups had no statistical difference in demographic and laboratory data. After treatment, serum zinc levels significantly increased in the zinc-treated group compared to the control group. Additionally, serum fibronectin and hyaluronic acid levels were significantly reduced in group 2 (zinc group) compared to group 1 (control group). Moreover, zinc group showed lower APRI scores than the control group after a 3-month follow-up period, but there was non-significant difference in FIB-4 scores between the two groups after treatment. Furthermore, total bilirubin levels were reduced after zinc therapy for 3 months. Conclusions Administering zinc sulfate could potentially serve as a safe and efficient therapeutic strategy for the management of hepatic fibrosis in individuals with chronic hepatitis C virus. Trial Registration ClinicalTrials.gov identifier: NCT05465434, On 19/7/2022.
Metformin as adjuvant therapy in obese knee osteoarthritis patients Amany Abd Elaal Aiad, Sahar Mohamed El-Haggar, Amal Mohamed El-Barbary, Dalia Refat El-Afify Inflammopharmacology, 2024 Aims This study aimed at investigating the efficacy of metformin as adjuvant therapy for obese knee osteoarthritis (OA) patients, considering its anti-inflammatory and cartilage-protective effects. Patients and methods In this randomized, double-blind, placebo-controlled study, 50 obese knee OA patients were assigned randomly to two groups, the metformin group (n = 25) which was treated with metformin 500 mg orally BID plus celecoxib 200 mg orally once daily, and the placebo group (n = 25) which was treated with placebo tablets BID plus celecoxib 200 mg orally once daily for 12 weeks. Cartilage Oligomeric Matrix Protein (COMP), C-terminal cross-linked telopeptide of type I collagen (CTX-1), and Interleukin 1-beta (IL-1β) serum levels were measured, while Western Ontario and McMaster Universities Arthritis Index (WOMAC) score assessed knee pain, stiffness, and physical function at baseline and after 12 weeks. Results Following a 12-week treatment, the metformin group exhibited significantly reduced levels of COMP, CTX-1, and IL-1β in the serum compared to the placebo group (p = 0.0081, p = 0.0106, and p = 0.0223, respectively). Furthermore, metformin group produced significant improvements in WOMAC total scale (p < 0.0001), specifically in knee pain, stiffness, and physical function compared to placebo group (p < 0.0001, p < 0.0001, and p < 0.0001, respectively). Conclusion Metformin as an adjuvant therapy in obese knee OA patients may have beneficial effects on cartilage degradation and inflammation, as evidenced by the significant decreases in serum COMP, CTX-1, and IL-1β levels. Additionally, metformin may improve clinical outcomes, as shown by the significant improvements in WOMAC scores. Clinicaltrials.gov ID NCT05638893/Registered December 6, 2022 — Retrospectively.
L-carnitine decreases myocardial injury in children undergoing open-heart surgery: A randomized controlled trial Wael El Feky, Dalia El-Afify, Dina Abdelhai, Mohamed Elkashlan, Ahmed Fakhreldin, et al. European Journal of Pediatrics, 2024 Myocardial injury in open-heart surgery is related to several factors including ischemia–reperfusion injury, generation of reactive oxygen species, increased production of inflammatory mediators, and enhancement of apoptosis of cardiomyocytes. The aim of this study was to study the effect of L-carnitine on myocardial injury in children undergoing open-heart surgery. This clinical trial was performed on 60 children with congenital heart disease (CHD) who underwent open-heart surgery. They were randomized into two groups: L-carnitine group who received L-carnitine 50 mg\\kg\\day once daily for 1 month before cardiac surgery and control group who received placebo for 1 month before cardiac surgery. Left ventricular cardiac function was assessed by conventional echocardiography to measure left ventricular ejection fraction (LVEF) and two-dimensional speckle tracking echocardiography (2D-STE) to determine left ventricular global longitudinal strain (2D-LV GLS). Blood samples were obtained pre-operatively at baseline before the administration of L-carnitine or placebo and 12 h post-operatively to measure the level of malondialdehyde (MDA), superoxide dismutase (SOD), fas, caspase-3, creatinine kinase-MB (CK-MB), and troponin I. L-carnitine group had significantly lower post-operative level of oxidative stress marker (MDA), apoptosis markers (fas and caspase-3), and myocardial injury markers (CK-MB and troponin I), but they had significantly higher SOD post-operative level compared to the control group. In addition, post-operative LVEF and 2D-LVGLS were significantly lower in the control group compared to L-carnitine group. Conclusion: L-carnitine can reduce myocardial injury, improve post-operative left ventricular cardiac function, and may provide myocardium protection in children with CHD who underwent open-heart surgery. Trial registration: The clinical trial was registered at www.pactr.org with registration number PACTR202010570607420 at 29/10/2020 before recruiting the patients. What is Known:• Myocardial injury in open-heart surgery is related to several factors including ischemia–reperfusion injury, generation of reactive oxygen species, increased production of inflammatory mediators, and enhancement of apoptosis of cardiomyocytes.• L-carnitine was reported to have myocardial protective effects in rheumatic valvular surgery and coronary artery bypass graft (CABG) in adults; however, there is no evidence on its effectiveness in children undergoing open-heart surgery. What is New:• L-carnitine significantly lowered the post-operative level of oxidative stress marker (MDA), apoptosis markers (fas and caspase-3), and myocardial injury markers (CK-MB and troponin I) in the treatment group.• L-carnitine can reduce myocardial injury, improve post-operative left ventricular cardiac function, and may provide myocardium protection in children with CHD who underwent open-heart surgery.
