The effect of Bromelain supplementation alone and in combination with Curcumin on disease symptoms and severity, inflammatory markers and oxidative stress in patients with Rheumatoid Arthritis

The effect of Bromelain supplementation alone and in combination with Curcumin on disease symptoms and severity, inflammatory markers and oxidative stress in patients with Rheumatoid Arthritis

A phase 3, randomized, triple-blind, controlled clinical trial conducted on 75 patients.

Blood samples will be collected twice from Rheumatoid Arthritis (RA) patients visiting Firoozgar Hospital who meet the inclusion criteria: once at baseline and once after the intervention, to assess the targeted factors.

Inclusion Criteria: 1. Willingness to participate and signing the informed consent form. 2. Age between 18 and 65 years. 3. Diagnosis of Rheumatoid Arthritis (RA) based on the American College of Rheumatology (ACR) criteria 4. Disease duration of at least two years. 5. No intake of dietary supplements (antioxidants, omega-3, etc.) in the past two months, except for routine supplements prescribed for Rheumatoid Arthritis (Vitamin D, Calcium, Vitamin A). 6. No history of diabetes, hypertension, acute cardiovascular diseases, thyroid disorders, kidney failure, or liver dysfunction based on the patient's medical history. 7. Stable medication regimen for at least one month before the study. 8. Not pregnant or breastfeeding 9. No use of contraceptive drugs. 10. No substance abuse. 11. Exclusion of individuals with allergies to pineapple, carrot, or fennel. 12. Exclusion of individuals taking anticoagulant medications.

Three groups of 25 RA patients: Bromelain (200 mg), Bromelain + Curcumin (200 mg + 300 mg), and Placebo (Maltodextrin).

TAC, MDA, CRP, ESR, TNF-α, IFN-γ, IL-17, disease severity, number of painful joints, number of inflamed joints, number of joints with tenderness, pain level, DAS28, joint stiffness

In this study, samples will be selected based on availability, and randomization will be performed for group allocation. For randomization, a random list for three groups, each with a sample size of 25 participants, was generated using web-based software. The letters A, B, and C will be assigned to the numbers 1 to 3 using random number generation. The numbers 1 to 3 correspond to the three groups: Group 1 (Bromelain), Group 2 (Bromelain + Curcumin), and Group 3 (Placebo). Based on the order of patient visits, the type of intervention, represented by letters A, B, and C, will be assigned to each patient according to the sequential list generated by the random number software. Patient selection will initially be based on their visits, making it a convenience sample, but drug allocation will be randomized.

This study is a triple-blind, placebo-controlled randomized clinical trial, meaning that the patient, the researcher, and the analysts performing the statistical analyses will remain unaware of the type of intervention until the analysis is completed. The pharmacist will attach labels A, B, and C to the medication packages, which will be provided to patients visiting the therapist according to the sequential list generated by the random number program. After the completion of the analysis and the review of the results, the pharmacist will be contacted to disclose the label assignments. This information will then be used in the preparation of the report and the manuscript, particularly in the findings, discussion, and conclusion sections.

Only a section of the data, such as primary outcomes information or the like, will be shared.

Access period start 5 months after results publishing.

The obtained data from current study will be available only for working researchers in academic and scientific institutions

5 months after the publicized papers from this study, the obtained data will be available to the researchers for further analysis.

Applicants can be communicated to correspond author be e-mail or postal address to receive the requested data. Postal address: Nutrition Department, School of Public Health, Iran University of Medical Sciences, Hemat Highway, Tehran Cell phone: +982186704743 Email: n-aryaeian@sina.tums.ac.ir

Publishing in scientific-research journals Applicants will be given access to the obtained data from current study by sending an email to correspond author.