Role of Nitazoxanide and Escitalopram in Patients With Rheumatoid Arthritis

NCT05480878 | Completed Phase 3

• 1 other identifier: Rheumatoid Arthritis
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Rheumatoid Arthritis

Keywords

Nitazoxanide; Escitalopram; STAT3/ JAK2 signaling pathway; TLR-4 /IL -1β signaling pathway

Outcome Measures

Primary Outcomes (5)

• 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 Outcomes (4)

• Determination of Signal transducer and activator of transcription 3 (STAT3) levels

  Baseline,12 weeks

• Determination of Toll-like receptor4 (TLR-4) levels

  Baseline,12 weeks

• Determination of interleukin-1β (IL-1β) levels

  Baseline, 12 weeks

• Determination of Malondialdehyde (MDA) levels

  Baseline, 12 weeks

Other Outcomes (1)

• Numbers of participants with treatment-related adverse events

  Baseline, 12 weeks

Study Arms (3)

Control

PLACEBO COMPARATOR

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

Drug: Placebo

Nitazoxanide

EXPERIMENTAL

Participants in this arm will receive Nitazoxanide 1 gm/day + DMARDs for 12 weeks.

Drug: Nitazoxanide 500Mg Oral Tablet

Escitalopram

EXPERIMENTAL

Participants in this arm will receive Escitalopram 10 mg/day + DMARDs for 12 weeks.

Drug: Escitalopram 10mg

Interventions

Placebo DRUG

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

Control

Nitazoxanide 500Mg Oral Tablet DRUG

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

Nitazoxanide

Escitalopram 10mg DRUG

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

Escitalopram

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Tanta University: lead

Study Sites (1)

Tanta university

Tanta, Egypt

Location

Related Publications (11)

• 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.

  PMID: 29417936 BACKGROUND

• 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.

  PMID: 21994179 BACKGROUND

• 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.

  PMID: 28562338 BACKGROUND

• 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.

  PMID: 33505220 BACKGROUND

• 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.

  PMID: 34955850 BACKGROUND

• 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.

  PMID: 34055214 BACKGROUND

• 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.

  PMID: 34533278 BACKGROUND

• 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.

  PMID: 20131240 BACKGROUND

• 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.

  PMID: 29656429 BACKGROUND

• 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.

  PMID: 20872595 BACKGROUND

• 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.

  PMID: 20617358 BACKGROUND

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

nitazoxanide; Tablets; Escitalopram

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Dosage Forms; Pharmaceutical Preparations; Propylamines; Amines; Organic Chemicals; Nitriles; Benzofurans; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant lecturer at clinical pharmacy department ,faculty of pharmacy, Tanta university

Study Record Dates

• First Submitted: July 23, 2022
• First Posted: July 29, 2022
• Study Start: December 2, 2022
• Primary Completion: March 25, 2023
• Study Completion: April 1, 2023
• Last Updated: April 25, 2023

Record last verified: 2023-04

Locations

EG (1)