Clinical trial NCT06915701: "Effect of Vitamin E (α-Tocopherol) on Clinical Activity and Inflammation in Rheumatoid Arthritis"
Official title: "Evaluation of the Effect of Vitamin E (α-tocopherol) Supplementation on Clinical Activity and Inflammation in Patients With Rheumatoid Arthritis"
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
PHASE3
Conditions: Rheumatoid Arthritis
Keywords: Rheumatoid arthritis
Antioxidant
Vitamin E
Lead sponsor: University of Guadalajara
Sponsor class: OTHER
Collaborators: name: Civil Hospital of Guadalajara
First posted: 2025-04-08
Enrollment: 46
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Definition of patients: will be patients with RA deficient in vitamin E consumption (\<15mg/day) , who are treated with conventional synthetic FARMEs (Methotrexate, Hydroxychloroquine, Leflunomide, Sulfasalazine and their combinations): The intervention group will take vitamin E 800mg/day, while the control group will take 200mg/day magnesium oxide placebo.
Primary purpose: TREATMENT

Brief summary: The objective of this clinical trial is to determine whether α-tocopherol (vitamin E) supplementation decreases inflammation and clinical activity in patients with rheumatoid arthritis (RA).The main questions to be answered are:

* Is supplementation with vitamin E (α-tocopherol) for one month associated with decreased clinical activity and inflammation in patients with RA?

Researchers will compare α-tocopherol with a placebo (a look-alike substance containing no active ingredient) to see if α-tocopherol effectively reduces inflammation and clinical activity in patients with rheumatoid arthritis.

Participants will:

* Take two capsules (one in the morning and one in the afternoon) of either α-tocopherol or placebo every day for a month.
* Attend clinic visits at the start of the intervention (baseline) and at the end of the month for final check-ups and tests.
* Keep a diary to record your symptoms and how often you take α-tocopherol or placebo.

Detailed description: Background:

Rheumatoid arthritis (RA) RA is one of the most common autoimmune diseases, characterized by chronic inflammation of the sinovia, mainly of the small joints of the hand, wrists and feet. Chronic inflammation can lead to the destruction of cartilage and joint bone, causing joint deformity, functional disability, depression and significant economic costs for the affected individual.

α-tocopherol acetate: The α-tocopherol acetate is the most widely used analogue in food supplements because of its esterification gives it stability. The main function is antioxidant preventing lipid oxidation of cell membranes for this reason α-tocopherol is considered a possible protector against diseases related to oxidative processes such as chronic diseasedegenerative diseases such as diabetes mellitus, cancer, cardiovascular disease, rheumatic disease, neurological disease and ageing.

Vitamin E in RA: The role of vitamin E as a therapy in combination with RA treatment has been studied in several studies. Studies in mouse models of laminarin-induced arthritis have shown that supplementation with α-tocopherol decreases the expression of pro-inflammatory cytokines such as IL-6, TNF-α and MMPs. However, the mechanisms involved are unknown. There are few studies in RA patients where the effect of supplementation with α-tocopherol has been analyzed. In clinical trials, it has been observed that from 3 weeks with supplementation of α-tocopherol decreases the scales of clinical activity in addition to morning stiffness and joint pain even biochemical parameters such as acute phase reactants such as pCr and ESR. However, the effect on pro-inflammatory cytokines, autoantibodies and antioxidant effect has not been analyzed.

Research question: Is supplementation with Vitamin E (α-tocopherol) for one month associated with decreased clinical activity and inflammation in patients with RA?

Specific objectives

1. Analyze the clinical characteristics and diet quality of RA patients
2. Determine serum autoantibody levels in RA patients
3. Quantify serum vitamin E levels before and after supplementation in both study groups (Vitamin E and placebo)
4. Compare clinical activity before and after supplementation in both study groups
5. Quantify serum concentration of pro-inflammatory cytokines IL1β, IL6 and TNF-α before and after supplementation in both study groups
6. Determine antioxidant capacity before and after supplementation in both study groups
7. Associate vitamin E levels with clinical and inflammatory parameters of patients with RA

Hypothesis :

There is an association between supplementation with vitamin E (α-tocopherol) and decreased clinical activity and inflammation in patients with RA from western Mexico

Methodological design:

a) Study type - Clinical, randomized, controlled and double-blind trial.

Research sites:

* Institute of Biomedical Sciences (IICB) of the University Center for Health Sciences (CUCS)
* Laboratory for Clinical Analysis and Translational Research (LACIT), at the University Center for Exact Sciences and Engineering (CUCEI)
* Rheumatology Service of the Civil Hospital "Fray Antonio Alcalde" in Guadalajara, Jalisco.

Time to develop: January 2025 to January 2027.

Sample size:

The statistical formula of two averages was used for the calculation of the sample size. The calculations were made with data from the corresponding 2001 clinical trial of Mona Helmy and colleagues, resulting in a sample size of 19 patients plus an increase of 20% to cover possible losses. Having 23 patients for control and intervention group. Both groups with RA of the Rheumatology Service of the Civil Hospital "Fray Antonio Alcalde" in Guadalajara, Jalisco.

Variables Independent variables

* Vitamin E Dependent variables
* Inflammatory cytokines (IL-1β, IL-6 and TNF-α). Antioxidant capacity:( DPPH, ABTS, FRAP and ORAC). Clinical evolution: DAS-28. Acute phase reactants: pCr and ESR. Auto-antibodies: Anti-ccp and rheumatoid factor.

Biosafety considerations:

This study will apply the guidelines set out in the Mexican Official Standards, NOM-052-SEMARNAT-2005, NOM-054-SEMARNAT-1993 and NOM-087-ECOL-SSA1-2002 that refer to classification, Handling, storage and disposal of hazardous waste, chemical reagents and biological-infectious wastes, in order to ensure the protection of people in contact with them and the environment.

Ethical considerations:

The project will be carried out in accordance with the ethical standards and principles for medical research on human beings, as set out in the Declaration of Helsinki, which were last reviewed at the 64th General Assembly, Fortaleza, Brazil, October 2013, which refers to ethical principles for medical research in humans.

Eligibility criteria: Inclusion criteria:

* Female sex
* RA classification (ACR/EULAR 2010)
* Early RA 2 years
* Treatment with conventional synthetic FARMEs (Metrotexato, Hydroxychloroquine, Leflunomide, Sulfasalazina and their combinations)
* DAS28 ≥3.2
* Vitamin E intake deficiency (\<15mg/day)
* No comorbidities
* Age \> 18 years
* Voluntary participation and informed consent.

Exclusion Criteria:

* Liver and kidney disease
* Overlap syndrome
* Coagulation disorders
* Pregnancy
* Consumption of supplements (iron, vitamin E, and K), and medications such as acetylsalicylic acid, amlodipine, estrogen, glucocorticoids and drugs used to treat dyslipidemias in the last three months.

Elimination Criteria:

* Errors in administration of the 20% supplement
* Adverse effects of the supplement
* Pregnancy during the study
* Insufficient blood sample
* Voluntary withdrawal of informed consent.

Primary outcomes:
measure: Levels of vitamin E
timeFrame: Exchange measures: Baseline and 1 month.
Secondary outcomes:
measure: Twenty-four hour reminder "questionnaire" (Recommended Daily Intake of Vitamin E)
timeFrame: Exchange measures: Baseline and 1 month.
measure: Levels of: Proinflammatory cytokines ( IL-1β , IL-6 and TNF-α )
timeFrame: Exchange measures: Baseline and 1 month.
measure: Antioxidant capacity: (DPPH, ABTS, FRAP and ORAC)
timeFrame: Exchange measures: Baseline and 1 month.
measure: Index DAS-28
timeFrame: Exchange measures: Baseline and 1 month.
measure: C-reactive protein (pCr)
timeFrame: Exchange measures: Baseline and 1 month.
measure: Erythrocyte sedimentation rate (ESR)
timeFrame: Exchange measures: Baseline and 1 month.
measure: Auto- antibodies: Anti-CCP
timeFrame: Exchange measures: Baseline and 1 month.
measure: Rheumatoid factor
timeFrame: Exchange measures: Baseline and 1 month.
Other outcomes:
Locations:
city: Guadalajara
country: Mexico
facility: Universidad de Guadalajara
state: Jalisco
Study officials:
affiliation: University of Guadalajara
name: Christian Johana J Baños Hernández, D.Sc.
role: PRINCIPAL_INVESTIGATOR
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