Role of Nitazoxanide and Escitalopram in Patients With Rheumatoid Arthritis

Clinical Study Evaluating the Efficacy of Nitazoxanide and Escitalopram as Adjuvant Therapies in Patients With Rheumatoid Arthritis

This study aims at evaluating the therapeutic effects of both Nitazoxanide and Escitalopram as adjuvant therapies in patients with Rheumatoid Arthritis and to evaluate their impact on STAT3/ JAK2, TLR /IL -1β signaling pathways.

This study is a randomized, controlled prospective study to evaluate the potential therapeutic effects of the broad -spectrum antimicrobial (Nitazoxanide) and selective serotonin reuptake inhibitor (Escitalopram) on synovial inflammation and angiogenesis when administered as add-on treatments to the current DMARDs treatments for rheumatoid arthritis patients. A total of 90 RA patients recruited from Outpatient Clinic of Physical Medicine, Rheumatology and Rehabilitation at Mansoura University hospitals, Mansoura, Egypt will be included in the study. They will be diagnosed with RA according to the American College of Rheumatology/European League Against Rheumatism criteria 2010 (the ACR/EULAR 2010 criteria). RA Patients who will meet the inclusion criteria will be enrolled in the study. They will be classified into three groups: Group 1: 30 RA patients who will receive the traditional therapy of rheumatoid arthritis for 12 weeks and serve as the control group. Group 2: 30 RA patients who will receive traditional therapy plus Nitazoxanide 1 gm/day for 12 weeks. Group 3: 30 RA patients who will receive traditional therapy plus Escitalopram 10 mg/day for 12 weeks. Clinical Examinations and laboratory parameters will be performed and measured at the beginning of the study and 3 months after randomization to evaluate the efficacy of Nitazoxanide and Escitalopram in the treatment of rheumatoid arthritis.

Participants in this arm will receive Placebo with the current DMARDs treatments for rheumatoid arthritis for 12 weeks. .

Placebo will be administered to the control group for 12 weeks as an add-on treatment to the current DMARDs treatments for rheumatoid arthritis.

All subjects will receive Nitazoxanide 500gm twice daily for 12 weeks as an add-on treatment to the current DMARDs treatments for rheumatoid arthritis.

All subjects will receive Escitalopram 10 mg/day for 12 weeks as an add-on treatment to the current DMARDs treatments for rheumatoid arthritis.

To evaluate the effect of the use of Nitazoxanide and Escitalopram as an add-on therapy in patients with rheumatoid arthritis by evaluating the change from baseline in the clinical findings as measured by Clinical Disease Activity Index (CDAI) scores. A lower CDAI score from Baseline would mean improvement in disease activity and an increase in CDAI score from Baseline would mean an increase in disease activity or a worsening in disease activity. Scores: 0.0-2.8 = Range for Remission; 2.9-10.0 = Range for Low disease activity; 10.1-22.0 Range for Moderate disease activity; 22.1-76 Range for High disease activity. Total range is from 0-100, with the high scores representing high disease activity.

Erythrocyte Sedimentation Rates (ESR) values will be made at baseline and after 12 weeks to determine the number of patients whose test result improved or worsened. ESR (normal range 0-28 mm/hr). If the value is increased, the disease activity worsened. If the value is reduced the disease activity is improved.

C- reactive Protein (CRP) values will be made at baseline and after 12 weeks to determine the number of patients whose test result improved or worsened. CRP value (normal range <1.0 mg/dl). If the value is increased, the disease activity worsened. If the value is reduced the disease activity is improved.

Rheumatoid factor (RF) values will be made at baseline and after 12 weeks to determine the number of patients whose test result improved or worsened. If the value is increased, the disease activity worsened. If the value is reduced the disease activity is improved.

Anti-cyclic citrullinated peptide (Anti-CCP) values will be made at baseline and after 12 weeks to determine the number of patients whose test result improved or worsened. If the value is increased, the disease activity worsened. If the value is reduced the disease activity is improved.

Serum STAT3 levels will be measured by means of the human enzyme-linked immunosorbent assay (ELISA) technique according to the manufacturers protocol

Serum TLR4 levels will be measured by means of the human enzyme-linked immunosorbent assay (ELISA) technique according to the manufacturers protocol.

Serum IL-1β levels will be measured by means of the human enzyme-linked immunosorbent assay (ELISA) technique according to the manufacturers protocol.

Serum MDA levels will be measured by means of the human enzyme-linked immunosorbent assay (ELISA) technique according to the manufacturers protocol

The adverse events in each group will be observed and documented during the whole procedure to show the safety of the treatment.

Inclusion Criteria: Diagnosed with rheumatoid arthritis according to the ACR/EULAR 2010 criteria. Receiving conventional disease modified anti rheumatic drugs (DMARDS). Having active disease (the 28-joint disease activity score [DAS28] according to the CRP formula > 2.6). Age between 18 and 75 years. Conscious and cooperative. Male or female. Sign an informed consent for the clinical study Exclusion Criteria: Pregnant or planning to be pregnant and breast-feeding women. Chronic disease. Other autoimmune diseases, such as systemic lupus erythematosus, Sjogren's syndrome and mixed connective tissue disease. Patients treated with biological TNF-α, IL6 or IL-1β antagonists. Infectious or inflammatory diseases, endocrine disorders, any past or current psychiatric or neurological diseases. Clinically significant hepatic and renal dysfunction or impairment. Alcohol abuse Receiving therapy that interact with Nitazoxanide and Escitalopram. Hypersensitivity to Nitazoxanide and Escitalopram.

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