Assessing the Impact of Herbal Supplement on Fatigue and Disease Activity in SLE: Results From an 8-Week Randomized Trial

Study Type:

This was a randomized, double-blind clinical trial conducted in two internal medicine departments in Tunisia over a period of 3 months.

Study Population:

Patients with a diagnosis of SLE who were being followed in the participating departments.

Inclusion criteria

Age superior than 18 years Confirmed diagnosis of SLE according to the 2019 ACR/EULAR classification criteria Presence of fatigue, defined as a FACIT-F score < 34 Signed informed consent

Non-Inclusion Criteria:

Pregnancy or breastfeeding Diseases or comorbidities that may influence fatigue:untreated hypothyroidism, psychosis common infections, and other autoimmune and inflammatory diseases Patients on vitamin K antagonist therapy, due to a possible interaction with Ginger and Nigella History of severe allergy or intolerance to EVACUR or any component of the placebo

Exclusion criteria

Diagnosis of another systemic disease during the study period Pregnancy Allergy to any component of EVACUR Withdrawal of consent

Data Collection:

Patient data were collected from medical records,including epidemiological characteristics such as age at inclusion , gender and medical and family history .Disease-specific data included the duration disease, systemic manifestations,nature of treatement at inclusion .Disease activity was evaluated using clinical SLEDAI-2K score. Baseline FACIT score was collected.Biological assessments were performed such us Anti-dsDNA antibody titers ,ANA and serum C3 and C4 levels.

Study protocol:

Randomization:

A two -to-one (2:1) randomization was performed in this study in which patients were randomly assigned into two groups: Group 1 (G1) which received EVACUR, and Group 2 (G2) received a placebo. Randomization was handled by an independent third party using a dedicated randomization software.

Double-Blind Design:

Neither the patients nor the investigators knew the treatment assignment. EVACUR and placebo capsules are identical in appearance.

Treatement:

EVACUR:

A phytotherapeutic compound presented in capsule form. Each bottle contains 40 capsules composed of: Nigella seed, Zinc sulfate, Echinacea, Vitamin C, Red ginseng, Ginger, Chamomile, Spirulina, Royal jelly, Ganoderma, Vitamins B1, B6, B12, Selenium(Table1).

Contra-indications: Allergy to any component of the supplement. Table 1. Ingredients and Dosage of EVACUR Formulation per Capsule Ingredient Latin/INCI Name Form/Quality Quantity per capsule Black seed Nigella sativa Dry extract 80 mg Echinacea Echinacea spp. Dry extract 40 mg Ginger Zingiber officinale Dry extract 30 mg Chamomile Matricaria chamomilla Dry extract 10 mg Red ginseng Panax ginseng Dry extract 10 mg Reishi mushroom Ganoderma lucidum Dry extract 10 mg Spirulina Spirulina spp. Dry extract 60 mg Royal jelly Royal jelly Lyophilized 20 mg Vitamin C Ascorbic acid - 30 mg Zinc Zinc sulfate - 2.5 mg Vitamin B1 Thiamine - 3 mg Vitamin B6 Pyridoxine Marine source 4 mg Vitamin B12 Cobalamin - 10 µg Selenium Selenium yeast - 40 µg

Placebo:

Capsules containing starch, packaged identically to EVACUR bottles. Both treatments will be administered at a dose of 2 capsules per day in the morning (3 bottles per patient for the study duration).

Follow-up:

Patients attended three visits at baselineM0, one monthM1, and two monthsM2. The FACIT score was assessed during each visit along with a physical examination.

Adverse Events:

Potential side effects will be recorded and evaluated throughout the study. Occurrence of any adverse event will lead to patient exclusion and trigger a pharmacovigilance investigation. All adverse events must be reported immediately to the principal investigator.

Fatigue Assessment Score:

Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) A 13-item questionnaire with responses on a Likert scale from 1 (not at all) to 5 (very much).

Total score out of 52; higher scores indicate less fatigue.Can be calculated if at least 50% of the questions are answered.

Reliability: High (Cronbach's alpha = 0.94) Validity: Strong, with good correlation with other fatigue measurement tools Completion time: 5-10 minutes A validated Arabic version is available with good psychometric properties .

Evaluation Criteria:

Primary Endpoint:

A mean Facit-F score improvement between G1 and G2 at month2 > Minimal Clinically Important Difference(MCID).The MCID in SLE is estimated at 3.4T[5].

Secondary Endpoints:

Improvement in the disease activity SLEDAI score Good tolerance of the dietary supplement.

Statistical Analysis:

Data were analyzed using SPSS.Appropriate statistical tests will be applied, including Student's t-test or the Wilcoxon test.Randomization will be conducted using dedicated software.

Inclusion criteria

• Age > 18 years
• Confirmed diagnosis of SLE according to the 2019 ACR/EULAR classification criteria
• Presence of fatigue, defined as a FACIT-F score < 34
• Signed informed consent

Non-Inclusion Criteria:

• Pregnancy or breastfeeding
• Diseases or comorbidities that may influence fatigue:untreated hypothyroidism, psychosis common infections, and other autoimmune and inflammatory diseases
• Patients on vitamin K antagonist therapy, due to a possible interaction with Ginger and Nigella
• History of severe allergy or intolerance to EVACUR or any component of the placebo

Exclusion criteria

• Diagnosis of another systemic disease during the study period
• Pregnancy
• Allergy to any component of EVACUR
• Withdrawal of consent