Role of Nitazoxanide and Escitalopram in Patients With Rheumatoid Arthritis

Rheumatoid Arthritis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05480878
• Other study ID #: Rheumatoid Arthritis
• Status: Completed
• Phase: Phase 3
• Start date: December 2, 2022
• Est. completion date: April 1, 2023

Study information

• Verified date: April 2023
• Source: Tanta University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 90
• Est. completion date: April 1, 2023
• Est. primary completion date: March 25, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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:

1. Pregnant or planning to be pregnant and breast-feeding women.

2. Chronic disease.

3. Other autoimmune diseases, such as systemic lupus erythematosus, Sjogren's syndrome and mixed connective tissue disease.

4. Patients treated with biological TNF-a, IL6 or IL-1ß antagonists.

5. Infectious or inflammatory diseases, endocrine disorders, any past or current psychiatric or neurological diseases.

6. Clinically significant hepatic and renal dysfunction or impairment.

7. Alcohol abuse

8. Receiving therapy that interact with Nitazoxanide and Escitalopram.

9. Hypersensitivity to Nitazoxanide and Escitalopram.

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• Placebo
Placebo will be administered to the control group for 12 weeks as an add-on treatment to the current DMARDs treatments for rheumatoid arthritis.
• Nitazoxanide 500Mg Oral Tablet
All subjects will receive Nitazoxanide 500gm twice daily for 12 weeks as an add-on treatment to the current DMARDs treatments for rheumatoid arthritis.
• Escitalopram 10mg
All subjects will receive Escitalopram 10 mg/day for 12 weeks as an add-on treatment to the current DMARDs treatments for rheumatoid arthritis.

Locations

Country	Name	City	State
Egypt	Tanta university	Tanta

Sponsors (1)

Lead Sponsor	Collaborator
Tanta University

Country where clinical trial is conducted

Egypt, 

References & Publications (11)

Aboudounya MM, Heads RJ. COVID-19 and Toll-Like Receptor 4 (TLR4): SARS-CoV-2 May Bind and Activate TLR4 to Increase ACE2 Expression, Facilitating Entry and Causing Hyperinflammation. Mediators Inflamm. 2021 Jan 14;2021:8874339. doi: 10.1155/2021/8874339. eCollection 2021. — View Citation

Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham CO 3rd, Birnbaum NS, Burmester GR, Bykerk VP, Cohen MD, Combe B, Costenbader KH, Dougados M, Emery P, Ferraccioli G, Hazes JM, Hobbs K, Huizinga TW, Kavanaugh A, Kay J, Kvien TK, Laing T, Mease P, Menard HA, Moreland LW, Naden RL, Pincus T, Smolen JS, Stanislawska-Biernat E, Symmons D, Tak PP, Upchurch KS, Vencovsky J, Wolfe F, Hawker G. 2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum. 2010 Sep;62(9):2569-81. doi: 10.1002/art.27584. — View Citation

Gong F, Shen T, Zhang J, Wang X, Fan G, Che X, Xu Z, Jia K, Huang Y, Li X, Lu H. Nitazoxanide induced myocardial injury in zebrafish embryos by activating oxidative stress response. J Cell Mol Med. 2021 Oct;25(20):9740-9752. doi: 10.1111/jcmm.16922. Epub 2021 Sep 17. — View Citation

Gupta S, Upadhayay D, Sharma U, Jagannathan NR, Gupta YK. Citalopram attenuated neurobehavioral, biochemical, and metabolic alterations in transient middle cerebral artery occlusion model of stroke in male Wistar rats. J Neurosci Res. 2018 Jul;96(7):1277-1293. doi: 10.1002/jnr.24226. Epub 2018 Apr 15. — View Citation

Li CH, Lu ZR, Zhao ZD, Wang XY, Leng HJ, Niu Y, Wang MP. Nitazoxanide, an Antiprotozoal Drug, Reduces Bone Loss in Ovariectomized Mice by Inhibition of RANKL-Induced Osteoclastogenesis. Front Pharmacol. 2021 Dec 9;12:781640. doi: 10.3389/fphar.2021.781640. eCollection 2021. — View Citation

Li Y, de Haar C, Peppelenbosch MP, van der Woude CJ. New insights into the role of STAT3 in IBD. Inflamm Bowel Dis. 2012 Jun;18(6):1177-83. doi: 10.1002/ibd.21884. Epub 2011 Oct 12. — View Citation

Lu Z, Li X, Li K, Wang C, Du T, Huang W, Ji M, Li C, Xu F, Xu P, Niu Y. Structure-Activity Study of Nitazoxanide Derivatives as Novel STAT3 Pathway Inhibitors. ACS Med Chem Lett. 2021 Apr 1;12(5):696-703. doi: 10.1021/acsmedchemlett.0c00544. eCollection 2021 May 13. — View Citation

Nishimoto N, Takagi N. Assessment of the validity of the 28-joint disease activity score using erythrocyte sedimentation rate (DAS28-ESR) as a disease activity index of rheumatoid arthritis in the efficacy evaluation of 24-week treatment with tocilizumab: subanalysis of the SATORI study. Mod Rheumatol. 2010 Dec;20(6):539-47. doi: 10.1007/s10165-010-0328-0. Epub 2010 Jul 10. — View Citation

Sacre S, Medghalchi M, Gregory B, Brennan F, Williams R. Fluoxetine and citalopram exhibit potent antiinflammatory activity in human and murine models of rheumatoid arthritis and inhibit toll-like receptors. Arthritis Rheum. 2010 Mar;62(3):683-93. doi: 10.1002/art.27304. — View Citation

Smolen JS, Aletaha D, Barton A, Burmester GR, Emery P, Firestein GS, Kavanaugh A, McInnes IB, Solomon DH, Strand V, Yamamoto K. Rheumatoid arthritis. Nat Rev Dis Primers. 2018 Feb 8;4:18001. doi: 10.1038/nrdp.2018.1. — View Citation

Wu X, Shou Q, Chen C, Cai H, Zhang J, Tang S, Cai B, Tang D, Cao G. An herbal formula attenuates collagen-induced arthritis via inhibition of JAK2-STAT3 signaling and regulation of Th17 cells in mice. Oncotarget. 2017 Jul 4;8(27):44242-44254. doi: 10.18632/oncotarget.17797. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Numbers of participants with treatment-related adverse events	The adverse events in each group will be observed and documented during the whole procedure to show the safety of the treatment.	Baseline, 12 weeks
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	Determination of interleukin-1ß (IL-1ß) levels	Serum IL-1ß levels will be measured by means of the human enzyme-linked immunosorbent assay (ELISA) technique according to the manufacturers protocol.	Baseline, 12 weeks
Secondary	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