Clinical trial NCT06716476: Impact of Vitamin D in Rheumatoid Arthritis
Official title: Impact of Vitamin D in Modulating Disease Activity and Inflammatory Mediators in Rheumatoid Arthritis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Rheumatic Arthritis
Keywords: Modulating Disease Activity and Inflammatory mediators
Lead sponsor: University of Pristina
Sponsor class: OTHER
First posted: 2024-12-04
Enrollment: 100
Sex: ALL
Minimum age (years): 30
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The goal of this prospective, randomized, parallel-group design, double-blind, and 6-month follow-up is to evaluate the impact of 4000 IU/day vitamin D on 25-hydroxyvitamin D \[25(OH)D\] levels and inflammatory mediators in people with Rheumatoid Arthritis (RA).

The main questions it aims to answer are

* The level of 25(OH)D and inflammatory mediators of levels of RA differs at baseline and after 6 months of Vitamin D 4000 UI
* The disease activity of AR measured by visual analogue scale (VAS) and Disease Activity Score-28 (DAS-28 score) will change in baseline and after 6 months of Vitamin D 4000 UI Researchers will compare the group of participants with Vitamin D supplementation and group of participants without D Vitamin supplementation

Participants in active group will:

* Take Vitamin D every day for 6 months
* Visit the clinic in the first months and after 6 months for medical visits and tests.

Detailed description: Rheumatoid arthritis (RA) is an idiopathic autoimmune disease with a chronic course of exacerbations and remissions with more frequent incidence in females, characterized by inflammation, pain, and progressive damage to the joints. The main focus of our study is to evaluate the impact of Vitamin D besides other standard therapies in the group of people with RA, assessing the inflammatory mediators and clinical course of the disease in the baseline and after six months.

This is a prospective, randomized, controlled Trial (RCT) with a Parallel-Group Design, ensuring that changes in inflammation markers and disease activity over time will be measured simultaneously and independently.

Before enrolment, the research dossier, including the patient's informed consent, was submitted to the Medical Chamber of Kosovo Ethics Committee for approval. This professional body approved this study, and the approval letter was issued to the research team. Patients were included in the study only after signing the consent form and after being fully informed about the research.

The participants will be patients which fulfils the diagnostic criteria for Rheumatoid Arthritis (RA) of American college of Rheumatology (ACR)/European league against rheumatism (EULAR) - ACR/EULAR 2010. The cohort of participants will be elected after evaluation of inclusion and exclusion criteria of participants:

The trial participants will be enrolled from a cohort of people with RA disease treated at the University Clinical Centre of Kosovo-Rheumatology Clinic in Prishtina. The data will be collected for one year.

In both group of participants at the baseline will be measured the level of 25-hydroxyvitamin D \[25(OH)D\] and inflammatory mediators of RA: Interleukin 6 (IL6) , Interleukin 17 (IL17), CRP, TNF-alpha). Moreover, in both groups participants will be determined the activity of disease measuring the visual analogue scale (VAS) and Disease Activity Score-28 (DAS-28 score). The intervention group of participants will receive the Vitamin D supplementation for 6 months while other group of participants will not receive the Vitamin D and after 6 months will be evaluated level of \[25(OH)D\] and inflammatory mediators of RA: Interleukin 6 (IL6) , Interleukin 17 (IL17), CRP, TNF-alpha) and VAS and Das28 and compare with baseline data.

Eligibility criteria: Inclusion criteria

* Rheumatoid Arthritis Caucasian patients,
* Kosovar ethnicity,
* Both genders,

Inclusion criteria:

* Patients with proven rheumatoid arthritis diagnosis ACR/EULAR 2010 grouped into four classifications with point scores for each:

  * joint symptoms;
  * serology (including RF and/or ACPA);
  * symptom duration, whether \<6 weeks or \>6 weeks; and
  * acute-phase reactants (CRP and/or ESR). Point scores ≥6/10 was criteria for AR diagnosis;
* RA disease duration 1-14 years

Exclusion criteria:

* Other inflammatory diseases;
* Thyroid and parathyroid diseases;
* Liver and kidney disease;
* Last 3 months treatment with Ca \> 1g/per day;
* Last 3 months treatment with vitamin D supplements

Primary outcomes:
measure: Level of 25(OH)D in serum
timeFrame: 6 months
measure: Serum level of inflammatory mediators of RA (IL6, IL17, CRP, TNF-alpha)
timeFrame: 6 months
Secondary outcomes:
measure: VAS: Visual analogue scale
timeFrame: 6 months
measure: DAS28: Disease Activity Score-28
timeFrame: 6 months
Other outcomes:
Locations:
city: Prishtina
country: Kosovo
facility: Faculty of Medicine University of Prishtina
Study officials:
References:
citation: Higgins MJ, Mackie SL, Thalayasingam N, Bingham SJ, Hamilton J, Kelly CA. The effect of vitamin D levels on the assessment of disease activity in rheumatoid arthritis. Clin Rheumatol. 2013 Jun;32(6):863-7. doi: 10.1007/s10067-013-2174-x. Epub 2013 Jan 23.
citation: Chandrashekara S, Patted A. Role of vitamin D supplementation in improving disease activity in rheumatoid arthritis: An exploratory study. Int J Rheum Dis. 2017 Jul;20(7):825-831. doi: 10.1111/1756-185X.12770. Epub 2015 Oct 20.
citation: Fassio A, Gatti D, Rossini M, Bertelle D, Bixio R, Viapiana O, Milleri S, Benini C, Pistillo F, Zanetti G, Adami G. Effects on Serum Inflammatory Cytokines of Cholecalciferol Supplementation in Healthy Subjects with Vitamin D Deficiency. Nutrients. 2022 Nov 14;14(22):4823. doi: 10.3390/nu14224823.
citation: Adams JS, Hewison M. Unexpected actions of vitamin D: new perspectives on the regulation of innate and adaptive immunity. Nat Clin Pract Endocrinol Metab. 2008 Feb;4(2):80-90. doi: 10.1038/ncpendmet0716.
citation: Al-Saoodi H, Kolahdooz F, Andersen JR, Jalili M. Effect of vitamin D on inflammatory and clinical outcomes in patients with rheumatoid arthritis: a systematic review and dose-response meta-analysis of randomized controlled trials. Nutr Rev. 2024 Apr 12;82(5):600-611. doi: 10.1093/nutrit/nuad083.
citation: Steiner G, Van Hoovels L, Csige D, Gatto M, Iagnocco A, Szekanecz Z. Should ACR/EULAR criteria be revised changing the RF and ACPA scores? Autoimmun Rev. 2024 Jan;23(1):103421. doi: 10.1016/j.autrev.2023.103421. Epub 2023 Aug 24.