Clinical trial NCT05261529: Effects of an Intervention With EVOO and Physical Activity in Patients With Systemic Lupus Erythematosus
Official title: Effects of a Nutricional Intervention With EVOO Oil and Physical Activity in Patients With Systemic Lupus Erythematosus: Effect on Clinical Course, Epigenetic and Microbiome
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Lupus Erythematosus, Systemic
Keywords: Mediterranean Diet
Olive Oil
Physical Exercise
Autoimmune Diseases
Systemic Lupus Erythematosus
Microbiome
Epigenetcis
Lead sponsor: Universidad de Granada
Sponsor class: OTHER
Collaborators: name: Consejería de Economía, Innovación y Ciencia. Proyectos de I+D+I en el marco operativo Feder Andalucía 2014-2020
First posted: 2022-03-02
Enrollment: 90
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Three-arm prospective randomized controlled 24-week clinical trial of patients diagnosed with SLE.
Primary purpose: SUPPORTIVE_CARE

Brief summary: In addition to the different pharmacological therapies available for the treatment of Systemic Lupus Erythematosus (SLE) as well as for its numerous associated complications (cutaneous, articular, hematological, neuropsychiatric, renal...), it has recently been proposed that 'health-related lifestyles' could have a determining role in balancing numerous organic processes at all levels. In line with this, the benefits of following a healthy dietary pattern such as the Mediterranean Diet and, specifically, the intake of Extra Virgin Olive Oil (EVOO) as well as the realization of regular physical exercise (PE) have been examined in numerous chronic non-communicable diseases such as obesity or cancer. However, in patients with autoimmune diseases, such as SLE, the possible effects of this synergy has not been investigated to date. Having demonstrated both the protective effect of a healthy dietary pattern and that of regular PE on the progression and risks associated with SLE in cross-sectional studies, non-intervention research has been developed that combines both strategies simultaneously, with nutritional supplementation or PE occurring independently. It is hypothesized that supplementation with EVOO in these patients together with PE will produce superior benefits compared to EVOO supplementation alone, showing changes in the phenotype of SLE and other parameters such as levels of chronicity/gravity, biomarkers (oxidative stress, immunological, inflammation), cardiovascular status and body composition.

Detailed description: SLE is one of the more representative autoimmune diseases that courses with several manifestations which are cutaneous-mucosal, joint, hematologic, neuropsychiatric and/or renal. In addition to the different pharmacological therapies available for its treatment, the adequate management of 'health-related lifestyles' becomes a relevant strategy by balancing, among others, the dysbiosis of the microbiota, the production of metabolites and the alteration of the immune response, with positive repercussions on all organic processes. Mediterranean Diet (MD), and the intake of EVOO in specific, which is its most representative food, has been shown to be a proven dietary pattern of protection against chronic non-communicable diseases. In line with this, Physical Exercise (PE) is another strategy on the rise. Regular exercise at moderate intensity has great impact on the immune system, the central nervous system, as a regulator of hormones and blood glucose levels, and on the psychosocial and cognitive spheres, ultimately leading to the appearance of numerous beneficial modifications in the face of external pathogenic aggressions and inflammatory processes.

Therefore, the synergy between DM and PE could enhance the known beneficial effects of both types of approaches in patients with SLE, as the scientific literature has shown in other chronic diseases such as obesity or cancer, among others. However, there are currently few studies that include PE interventions, and there is also some contradiction in the results. In addition, there is no study that synergizes both approaches in a coincident manner over time. The present study, whose main objective is to analyze the influence of the addition to a supplementation with EVOO of a multimodal combined physical exercise intervention in patients with SLE, is developed under the hypothesis that: The combination of dietary supplementation with EVOO together with the follow-up of a multimodal PE program will result in superior benefits in SLE patients with respect to a group of patients solely supplemented with EVOO, showing changes in SLE phenotype and parameters such as levels of chronicity/severity of the disease, levels of biochemical, immunological, inflammatory and oxidative stress markers, markers of cardiovascular risk and early atherosclerosis and endothelial function, cardiorespiratory status and body composition.

For this purpose, a 24-week clinical trial will be developed with three groups of patients with SLE (30 patients/group): a control group (no intervention), another that will add to the usual intake pattern of 40ml of EVOO daily during 24 weeks, and a third group that will add to this additional intake of EVOO the follow-up of a specific PE program in the middle of the intervention (12 weeks).

Data collection in all groups will be perform before the intervention, at an intermediate stage and coinciding with the beginning of the PE program (12 weeks), and at the end of the study (24 weeks).

The study will be carried out in three phases:

STAGE 1: Reinforcement of adherence to DM. In order to guarantee during the intervention the maintenance of the levels of adherence to DM established as inclusion criteria, previously and in both groups the basic principles of DM will be recalled by a nutritionist, through group sessions of 1 hour of duration.

STAGE 2: Intervention. EVOO supplementation, or EVOO supplementation + PE under the conditions previously described. The intervention, which will be extended over 24 weeks, will consist of the daily consumption of 40 ml of EVOO in a single daily intake, added to the usual intake pattern of the participants.

* CG. The participants' usual lifestyle (dietary pattern and physical activity) will not be modified.
* Intervention Group 1. Patients will take the EVOO supplementation as describe below, without changing their physical activity routines.
* Intervention Group 2. In addition to taking EVOO supplementation, patients will start following a Multimodal Physical Exercise (MFE) program during the remaining 12 weeks of intervention, guided by personnel with experience in the area: 3 days per week, groupal sessions (≤10 participants/group) on non-consecutive days, both online and face-to-face sessions. Continuous (4-6weeks) and intervallic (week 5-7 to 24) cardiovascular exercise will be worked at moderate-intense intensity, controlled by HR in reserve, with a duration of 15-45 minutes. In addition, sympathetic modulation exercises (stretching, breathing, meditation) will be used as methods to promote recovery, with a duration of 10-30 minutes. In this group, supplementation will take place after exertion.

STAGE 3: Post-intervention data collection (week 25).

Eligibility criteria: Patients will be eligible if they have been diagnosed with SLE for at least one year and have been seen at the Outpatient Clinic of the Systemic Autoimmune Diseases Unit of the Hospital Universitario Clínico San Cecilio of Granada (Spain), meet the revised American College of Rheumatology (ACR), SLICC or ACR/EULAR criteria of 2019 and maintain a stable SLEDAI-2K, without treatment modifications, in the previous 3 months.

Inclusion Criteria:

* Medium (8 to 11 points) to high (12 to 14 points) level of adherence to DM as measured by the 14-point DM adherence scale of the PREDIMED study.
* Sedentary, inactive or non-performing subjects of structured PE (+5h sitting or doing less than 300min of weekly physical activity or \<60min structured exercise per week).

Exclusion Criteria:

* Terminal stages of the disease
* Serum creatinine levels ≥1.5mg / dl
* Type 1 Diabetes Mellitus
* Infection, trauma or surgery six months prior to intervention
* SLICC\> 5
* Pregnant, with intention, or breastfeeding
* Diagnosis of other autoimmune / inflammatory diseases
* Participation in other PE guided programs
* Contraindication for PE: psychiatric or cognitive disorders, acute or chronic conditions (advanced lung disease, high requirements, stenosis\> 70%)
* BMI of morbid obesity (≥40)

Primary outcomes:
measure: SLEDAI Systemic Lupus Erythematosus Disease Activity Index
timeFrame: Participants will be followed over 24 weeks.
Secondary outcomes:
measure: Cumulative manifestations
timeFrame: Participants will be followed over 24 weeks.
measure: SLICC/ACR (Systemic Lupus International Collaborating clinics/American College of Rheumatology) Damage Index for Systemic Lupus Erythematosus.
timeFrame: Participants will be followed over 24 weeks.
measure: Pharmacological prescription
timeFrame: Participants will be followed over 24 weeks.
measure: Glucose level
timeFrame: Participants will be followed over 24 weeks.
measure: Urea level
timeFrame: Participants will be followed over 24 weeks.
measure: Creatinine level
timeFrame: Participants will be followed over 24 weeks.
measure: Lipid profile analysis
timeFrame: Participants will be followed over 24 weeks.
measure: Creatine Kinase concentration
timeFrame: Participants will be followed over 24 weeks.
measure: Hemoglobin concentration
timeFrame: Participants will be followed over 24 weeks.
measure: Number of lymphocytes
timeFrame: Participants will be followed over 24 weeks.
measure: Number of platelets
timeFrame: Participants will be followed over 24 weeks.
measure: Number of leukocytes
timeFrame: Participants will be followed over 24 weeks.
measure: Inflammation
timeFrame: Participants will be followed over 24 weeks.
measure: Anti phospholipid antibodies concentration
timeFrame: Participants will be followed over 24 weeks.
measure: Double-stranded anti-DNA antibodies concentration
timeFrame: Participants will be followed over 24 weeks.
measure: Complement fraction C3 concentration
timeFrame: Participants will be followed over 24 weeks.
measure: Complement fraction C4 concentration
timeFrame: Participants will be followed over 24 weeks.
measure: Cardiorespiratory Fitness
timeFrame: Participants will be followed over 24 weeks.
measure: Functional capacity
timeFrame: Participants will be followed over 24 weeks.
measure: Hight
timeFrame: Participants will be followed over 24 weeks.
measure: Weight
timeFrame: Participants will be followed over 24 weeks.
measure: Skeletal Muscle Mass
timeFrame: Participants will be followed over 24 weeks.
measure: Body Fat Mass
timeFrame: Participants will be followed over 24 weeks.
measure: Body Mass Index
timeFrame: Participants will be followed over 24 weeks.
measure: Body Fat Index
timeFrame: Participants will be followed over 24 weeks.
measure: Waist-to-hip ratio in centimeters
timeFrame: Participants will be followed over 24 weeks.
measure: Obesity degree
timeFrame: Participants will be followed over 24 weeks.
measure: Body Cell Mass
timeFrame: Participants will be followed over 24 weeks.
measure: Bone Mineral Content
timeFrame: Participants will be followed over 24 weeks.
measure: Basal Metabolic Rate
timeFrame: Participants will be followed over 24 weeks.
measure: Visceral Fat Area
timeFrame: Participants will be followed over 24 weeks.
measure: Bone density
timeFrame: Participants will be followed over 24 weeks.
measure: Human Vascular Cell Adhesion Molecule-1 concentration
timeFrame: Participants will be followed over 24 weeks.
measure: Intercellular Adhesion Molecule-1concentration
timeFrame: Participants will be followed over 24 weeks.
measure: E-Selectin concentration
timeFrame: Participants will be followed over 24 weeks.
measure: Super Oxide Dismutase concentration
timeFrame: Participants will be followed over 24 weeks.
measure: Glutathione concentration
timeFrame: Participants will be followed over 24 weeks.
measure: Total Antioxidant Capacity concentration
timeFrame: Participants will be followed over 24 weeks.
measure: Thiobarbituric Acid Reactive Substances concentration
timeFrame: Participants will be followed over 24 weeks.
measure: Malondialdehyde concentration
timeFrame: Participants will be followed over 24 weeks.
measure: Advanced Oxidation Protein Products concentration
timeFrame: Participants will be followed over 24 weeks.
measure: Total proteins concentration
timeFrame: Participants will be followed over 24 weeks.
measure: Endothelial Function
timeFrame: Participants will be followed over 24 weeks.
measure: miRNA expression profile quantification
timeFrame: Participants will be followed over 24 weeks.
measure: Microbiome characteristics analysis
timeFrame: Participants will be followed over 24 weeks.
Other outcomes:
Locations:
city: Granada
country: Spain
facility: Universidad de Granada
state: Granada, Spain
Study officials:
affiliation: Universidad de Granada
name: María Correa Rodríguez, Professor
role: PRINCIPAL_INVESTIGATOR
References:
citation: Pocovi-Gerardino G, Correa-Rodriguez M, Callejas-Rubio JL, Rios-Fernandez R, Martin-Amada M, Cruz-Caparros MG, Rueda-Medina B, Ortego-Centeno N. Beneficial effect of Mediterranean diet on disease activity and cardiovascular risk in systemic lupus erythematosus patients: a cross-sectional study. Rheumatology (Oxford). 2021 Jan 5;60(1):160-169. doi: 10.1093/rheumatology/keaa210.