Oxidative Stress in Autoimmune Rheumatic Diseases (REDOX-ARD)

Investigation of the Role of Redox Status of Patients With Autoimmune Rheumatic Diseases on Disease Progression: An Epidemiological Study

Rheumatic diseases constitute a group of non-communicable diseases characterized by chronic inflammation. The most common autoimmune rheumatic diseases (ARDs) are rheumatoid arthritis, psoriatic arthritis, systemic lupus erythematosus, myositis, Sjogren's syndrome and systemic scleroderma. These autoimmune disorders lead to joint destruction and adversely influence the human body systemically. One of their characteristics is comorbidity, since patients usually suffer also from other pathologies such as cardiovascular diseases and obesity. In addition, their treatment requires a combination of both biological and conventional pharmaceutical interventions as well as other parameters such as physical activity programs, nutrition, and the use of smart electronic devices. Therefore, the ARDs burden health systems worldwide. Apart from the physiological manifestations of ARDs, specific changes are observed at the cellular and molecular level. A common biochemical/molecular symptom of these diseases is oxidative stress. This condition leads to the disturbance of blood and tissue redox status due to the excessive production of free radicals. Given that free radicals are highly reactive moieties with strong oxidative capacity against biomolecules (i.e., proteins, lipids, DNA), they compromise the efficacy of the intrinsic antioxidant mechanisms and, finally, induce the disruption of redox homeostasis. However, there is no sufficient data linking the levels of redox status of patients with the progression of ARDs over time. Indeed, the onset and symptoms of ARDs are intertwined with the disruption of the patient redox homeostasis and the induction of oxidative stress. Concurrently, the absence of a completely effective pharmaceutical treatment emerges the need for the adoption of novel biomarkers for monitoring the severity of the symptoms and the evolution of ARDs in general. To that end, this study aims at first to investigate the blood redox status of patients with ARDs. Thus, specific redox biomarkers will be evaluated in the blood of patients in three time points (i.e., at Days 1, 180 and 360), and they will be associated with the clinical manifestations of their diseases. The ultimate goal is to clarify whether these biomarkers could putatively exert clinical significance, namely whether they could constitute an additional tool for the monitoring of the progression of these diseases in clinical practice.

Study Overview

• Status: Recruiting
• Conditions: Rheumatoid Arthritis (RA); Ankylosing Spondylitis (AS); Psoriatic Arthritis (PsA); Inflammatory Joint Diseases

Detailed Description

Background: In recent years, there has been a significant increase in the incidence of chronic inflammatory non-communicable diseases worldwide, which are responsible for 71% of deaths annually. The prevention of these diseases has been associated with dietary habits and physical activity, while their auxiliary use along with the appropriate pharmaceutical interventions can also contribute to the reduction of their severity. Autoimmune rheumatic diseases (ARDs) are a group of non-communicable diseases characterized by chronic inflammation, that lead to joint destruction, and adversely affect human body. The most common ARDs are rheumatoid arthritis, psoriatic arthritis, systemic lupus erythematosus, myositis, Sjogren's syndrome and systemic scleroderma. The etiology of ARDs is rather complex. It is noteworthy that significant side effects are observed in patients receiving specific drug therapy, while some of them are resistant to existing drugs. According to available data, the incidence of rheumatic diseases is estimated at 0.5-1%. However, these diseases particularly burden health systems on a global scale. This is the case not only because one of their characteristics is comorbidity, since patients usually suffer from other diseases such as cardiovascular diseases and obesity, but also because of the use of biological medicines. On this basis, their management requires a combination of biological and conventional pharmaceutical interventions, as well as other parameters such as physical activity programs, nutrition and the use of smart electronic devices. Along with the physiological manifestations of ARDs, they share a biochemical/molecular symptom, namely oxidative stress. Oxidative stress is a condition that consists of the disturbance of redox state of blood and tissues due to the excessive production of free radicals. The latter are highly reactive molecules or atoms able to oxidize biomolecules (i.e., proteins, lipids, DNA). Specifically, in oxidative stress context, the concentration of blood antioxidant molecules is reduced, making biomolecules susceptible to potential oxidation and, therefore, to damage of their normal function. Oxidative stress is associated to inflammation and, therefore, is observed in ARDs by affecting normal cell signaling and disrupting redox homeostasis. Nevertheless, to our knowledge, there is no available data linking the levels of blood redox status of patients with the progression of ARDs over time. Methods: The levels of specific and widely established redox biomarkers will be evaluated in blood samples of the volunteering patients in three time points (i.e., Days 1, 180 and 360) to assess their blood redox status. The battery of the redox biomarkers that will be measured is as follows: The concentration of reduced form of glutathione (GSH) which is a crucial antioxidant metabolite, the activity of catalase, a potent antioxidant enzyme, total antioxidant capacity (TAC) as a crude indicator of blood antioxidant potential and concentration of protein carbonyls as a biomarker of protein oxidation. Moreover, C-reactive protein and erythrocyte sedimentation rate as indices of inflammation of the volunteers, as well as the severity of the ARDs through DAS28, PASI and SLEDAI tools will also be estimated. Finally, data regarding the following parameters will be collected: i) physical activity through the international physical activity questionnaire, ii) health status through the health assessment questionnaire, iii) quality of life through the Nottingham health profile questionnaire, iv) fatigue through the fatigue severity scale instrument and by using a visual analogue scale, v) sleep quality through the Pittsburgh sleep quality index and vi) nutritional habits through an one-day recall diary. Finally, the medication history of every patient as well as possible changes in medication will also be recorded. Anticipated outcomes: The levels of redox biomarkers will, at first, give insight about the baseline (i.e., at Day 1) oxidant/antioxidant state in the blood of the patients. In addition, blood redox biomarkers will be correlated to all measured parameters and their potential to diagnose/project the progression of ARDs will be examined. It is expected that blood redox biomarkers could serve as putative diagnostic tools regarding the progression of ARDs and the change in medication.

• Study Type: Observational
• Enrollment (Estimated): 200

Contacts and Locations

Study Locations

• Greece
  • Thessaly
    • Larissa, Thessaly, Greece
      • Recruiting
      • General University Hospital of Larissa. Greece
      • Contact: Karaventza Marianthi; Phone Number: 0030 6972758418; Email: markaraventza@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

The study population comprises patients of the General University Hospital of Larissa

Description

Inclusion Criteria:

• Adult patients (>18 years old), with a primary diagnosis of rheumatoid arthritis using the criteria of American College of Rheumatology (ACR)
• Adult patients (>18 years old), with a primary diagnosis of psoriatic arthritis using the ClASsification criteria for Psoriatic Arthritis (CASPAR)
• Adult patients (>18 years old), with a primary diagnosis of alkylosing spondyloarthritis using the criteria of Assessment of SpondyloArthritis international Society (ASAS) group
• Adult patients (>18 years old) irrespective of gender
• Adult patients (>18 years old) irrespective of ethnicity
• Adult patients (>18 years old) irrespective of comorbidities
• Adult patients (>18 years old) irrespective of socioeconomic background
• Adult patients (>18 years old) with any disease status
• Adult patients (>18 years old) with any disease duration
• Adult patients (>18 years old) under any treatment scheme (e.g. non-steroidal anti-inflammatory drugs, steroids, disease-modifying anti-rheumatic drugs including biologics)

Exclusion Criteria:

• Adult patients (>18 years old) with concurrent infectious disease
• Adult patients (>18 years old) in pregnancy
• Patients under 18 years of age

Study Plan

How is the study designed?

Number of groups / cohorts

5

Cohorts and Interventions

Group / Cohort
Patients with rheumatoid arthritis; No intervention
Patients with psoriatic arthritis; No intervention
Patients with ankylosing spondylitis; No intervention
Patients with systemic lupus erythematosus; No intervention
Patients with scleroderma; No intervention

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Concentration of blood reduced glutathione (GSH)	The concentration of reduced form of glutathione (GSH) as a crucial intrinsic antioxidant metabolite will be measured spectrophotometrically in erythrocytes.	GSH concentration will compared between Day 1 and Days 180 and 360

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Concentration of protein carbonyls in blood	The concentration of protein carbonyls, as a biomarker of protein oxidation, will be evaluated spectrophotometrically in plasma.	Protein carbonyl concentration will compared between Day 1 and Days 180 and 360
Total antioxidant capacity (TAC) of blood	TAC is a crude biomarker of antioxidant capacity of blood	TAC will be compared between Day 1 and Days 180 and 360
Activity of erythrocyte catalase	Catalase is a primary antioxidant enzyme	Catalase activity will be compared between Day 1 and Days 180 and 360
Concentration of C-reactive protein (CRP) in blood	CRP is an established biomarker of acute inflammation	CRP conentration will be compared between Day 1 and Days 180 and 360
Erythrocyte sedimentation rate	Erythrocyte sedimentation rate is an index of inflammation	Erythrocyte sedimentation rate will be compared between Day 1 and Days 180 and 360]
Severity of rheumatoid arthritis	It will be evaluated with the disease activity score 28 (DAS28). It combines 4 components, namely tender joint count, swollen joint count, inflammation and patient global assessment with a 0-100 VAS scale (0 = very good, 100 = very bad).	Data of DAS28 will be compared between Day 1 and Days 180 and 360
Severity of psoriatic arthritis	It will be evaluated with the psoriasis area and severity Index (PASI). It combines 2 components, namely, severity of skin lesions and area of skin affected. Higher final score implies more severe symptoms.	Data of PASI will be compared between Day 1 and Days 180 and 360
Severity of alkylosing spondyloarthritis	It will be evaluated with the SLE disease activity index (SLEDAI). It assesses clinical manifestations and laboratory findings in a scale 1 (less severe) - 8 (more severe).	Data of SLEDAI will be compared between Day 1 and Days 180 and 360
Physical activity levels	It will be measured through the international physical activity questionnaire (IPAC). Data for minutes of vigorous activity, moderate activity, walking and sitting time is collected. According to the obtained mean exercise time, physical activity levels are considered as high, moderate or low.	Physical activity levels will be compared between Day 1 and Days 180 and 360
Health status	Health status will be evaluated through the health assessment questionnaire	Health status will be compared between Day 1 and Days 180 and 360
Fatigue levels	It will be measured through the fatigue severity scale (FSS). FSS is a 9-item, self-administered questionnaire which assesses the magnitude of fatigue that the volunteers have experienced throughout the past weeks. Each item is scored on a 7-point Likert scale ranging from 1 (i.e., completely disagree) to 7 (i.e., completely agree). High values = more severe fatigue.	Fatigue levels will be compared between Day 1 and Days 180 and 360
Sleep quality	It will be measured through the Pittsburgh sleep quality index (PSQI). PSQI is a 19-item self-reported questionnaire, which assesses sleep quality and quantity, sleep habits related to quality and occurrence of sleep disturbances consisting of 7 components. Each component score is marked on a 0-3 scale, and the PSQI is calculated as the sum of the 7 components ranging between 0 and 21. Higher final score = better sleep quality.	Sleep quality levels will be compared between Day 1 and Days 180 and 360
Nutritional habits	Nutritional habits will be recorded through an one-day recall diary	Nutritional habits will be compared between Day 1 and Days 180 and 360
Demographic data	Body mass index, smoking, alcohol consumption, place of residence, health insurance, educational status, family status and financial status will be collected among others through a questionnaire.	Demographic data will be compared between Day 1 and Days 180 and 360
Quality of life	It will be measured through the SF-36 questionnaire. This instrument has a physical component and a mental component. In particular, SF-36 assesses the following health parameters of the participants: Physical functioning, Role limitations due to physical health, Bodily pain, General health perceptions, Vitality, Social functioning, Role limitations due to emotional problems and Mental health. Each domain is scored from 0 to 100. Higher score = better health or better quality of life.	The measured parameters of the quality of life of the volunteers will be compared between Day 1 and Days 180 and 360

Collaborators and Investigators

• Sponsor: University of Thessaly
• Collaborators: Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece; George Metsios, Professor, Department of Nutrition and Dietetics, University of Thessaly, Greece; General University Hospital of Larissa; Dimitrios P. Bogdanos, Professor, Department of Rheumatology and Clinical Immunology, Larissa University Hospital

Publications and helpful links

General Publications

• Phull AR, Nasir B, Haq IU, Kim SJ. 2018. Oxidative stress, consequences and ROS mediated cellular signaling in rheumatoid arthritis. Chemico-biological interactions, 281, 7, 121-136.
• Nitschke E, Gottesman K, Hamlett P, Mattar L, Robinson J, Tovar A, Rozga M. 2022. Impact of Nutrition and Physical Activity Interventions Provided by Nutrition and Exercise Practitioners for the Adult General Population: A Systematic Review and Meta-Analysis. Nutrients, 14(9): 1729.
• World Health Organization Physical Activity 2022β. Available online: https://www.who.int/news-room/fact-sheets/detail/physical-activity.
• World Health Organization Noncommunicable Diseases 2022α. Available online: https://www.who.int/news-room/fact-sheets/detail/noncommunicable-diseases.

Study record dates

Study Major Dates

• Study Start (Actual): October 6, 2025
• Primary Completion (Estimated): April 30, 2026
• Study Completion (Estimated): October 1, 2026

Study Registration Dates

• First Submitted: April 6, 2026
• First Submitted That Met QC Criteria: April 11, 2026
• First Posted (Actual): April 17, 2026

Study Record Updates

• Last Update Posted (Actual): April 28, 2026
• Last Update Submitted That Met QC Criteria: April 22, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Antioxidants; Oxidative stress; Psoriatic arthritis; Rheumatoid arthritis; Ankylosing spondylitis
• Additional Relevant MeSH Terms: Axial Spondyloarthritis; Bone Diseases; Musculoskeletal Diseases; Arthritis; Joint Diseases; Rheumatic Diseases; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Spinal Diseases; Spondylarthropathies; Ankylosis; Skin Diseases, Papulosquamous; Skin Diseases; Spondylarthritis; Spondylitis; Psoriasis; Skin and Connective Tissue Diseases; Spondylitis, Ankylosing; Arthritis, Rheumatoid; Arthritis, Psoriatic
• Other Study ID Numbers: 72/8.01.2025; 42339/17/10/2024 (Other Identifier: Scientific Board of the General University Hospital of Larissa, Greece)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No