Role of Nitazoxanide and Escitalopram in Patients With Rheumatoid Arthritis

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Drug: Placebo
* Drug: Nitazoxanide 500Mg Oral Tablet
* Drug: Escitalopram 10mg


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Control<br>Participants in this arm will receive Placebo with the current DMARDs treatments for rheumatoid arthritis for 12 weeks. . | Drug: Placebo<br>* Placebo will be administered to the control group for 12 weeks as an add-on treatment to the current DMARDs treatments for rheumatoid arthritis.<br>|
| Experimental: Nitazoxanide<br>Participants in this arm will receive Nitazoxanide 1 gm/day + DMARDs for 12 weeks. | Drug: Nitazoxanide 500Mg Oral Tablet<br>* All subjects will receive Nitazoxanide 500gm twice daily for 12 weeks as an add-on treatment to the current DMARDs treatments for rheumatoid arthritis.<br>|
| Experimental: Escitalopram<br>Participants in this arm will receive Escitalopram 10 mg/day + DMARDs for 12 weeks. | Drug: Escitalopram 10mg<br>* All subjects will receive Escitalopram 10 mg/day for 12 weeks as an add-on treatment to the current DMARDs treatments for rheumatoid arthritis.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes from Baseline in Clinical Disease Activity Index (CDAI) Score | 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. | Baseline, 12 weeks | 
| Changes in Erythrocyte Sedimentation Rates (ESR) | 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. | Baseline, 12 weeks | 
| Changes in C- reactive Protein (CRP) | 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. | Baseline,12 weeks | 
| Changes in Rheumatoid factor (RF) values | 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. | Baseline,12 weeks | 
| Changes in Anti-cyclic citrullinated peptide (Anti-CCP) values | 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. | Baseline,12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determination of Signal transducer and activator of transcription 3 (STAT3) levels | Serum STAT3 levels will be measured by means of the human enzyme-linked immunosorbent assay (ELISA) technique according to the manufacturers protocol | Baseline,12 weeks | 
| Determination of Toll-like receptor4 (TLR-4) levels | Serum TLR4 levels will be measured by means of the human enzyme-linked immunosorbent assay (ELISA) technique according to the manufacturers protocol. | Baseline,12 weeks | 
| Determination of interleukin-1β (IL-1β) levels | Serum IL-1β levels will be measured by means of the human enzyme-linked immunosorbent assay (ELISA) technique according to the manufacturers protocol. | Baseline, 12 weeks | 
| Determination of Malondialdehyde (MDA) levels | Serum MDA levels will be measured by means of the human enzyme-linked immunosorbent assay (ELISA) technique according to the manufacturers protocol | Baseline, 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Nitazoxanide, Escitalopram, STAT3/ JAK2 signaling pathway, TLR-4 /IL -1β signaling pathway