Effects of an Intervention With EVOO and Physical Activity in Patients With Systemic Lupus Erythematosus

Lupus Erythematosus, Systemic Clinical Trial

— EFINUTRILES  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05261529
• Other study ID #: 2099-N-21
• Status: Recruiting
• Phase: N/A
• Start date: November 3, 2021
• Est. completion date: June 30, 2023

Study information

• Verified date: December 2022
• Source: Universidad de Granada
• Contact: María Corea Rodríguez, Professor
• Phone: 958243494
• Email: macoro[@]ugr.es
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 90
• Est. completion date: June 30, 2023
• Est. primary completion date: December 30, 2022
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 70 Years

Eligibility

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)

Related Conditions & MeSH terms

• Lupus Erythematosus, Systemic

Intervention

Dietary Supplement:
• Extra Virgin Olive Oil (EVOO)
Daily intake of 40ml EVOO added to the normal intake of EVOO of the participants.

Behavioral:
• Physical Exercise Program
Besides the EVOO supplementation in the same conditions as the 'Intervention 1 Group', participants will add the follow-up of a Multimodal Physical Exercise (MFE) program during the remaining 12 weeks of intervention, 3 days per week, online and face-to-face group sessions on non-consecutive days. Continuous and intervalic cardiovascular exercise at moderate-intense intensity, controlled by the HR in reserve, with a duration of 15-45 minutes, also including sympathetic modulation exercises (stretching, breathing and meditation) and methods to promote recovery, with a duration of 10-30 minutes.

Locations

Country	Name	City	State
Spain	Universidad de Granada	Granada	Granada, Spain

Sponsors (2)

Lead Sponsor	Collaborator
Universidad de Granada	Consejería de Economía, Innovación y Ciencia. Proyectos de I+D+I en el marco operativo Feder Andalucía 2014-2020

Country where clinical trial is conducted

Spain, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	SLEDAI Systemic Lupus Erythematosus Disease Activity Index	SLE-specific index that assess disease activity through a combination of data from clinical records, physical examination, organ-specific functional tests and serological studies.	Participants will be followed over 24 weeks.
Secondary	Cumulative manifestations	All the manifestations and complications that patients go through or appear during the intervention, recorded by interview with clinicians.	Participants will be followed over 24 weeks.
Secondary	SLICC/ACR (Systemic Lupus International Collaborating clinics/American College of Rheumatology) Damage Index for Systemic Lupus Erythematosus.	Index developed to quantify damage that has occurred since onset of lupus, correlates with mortality. Score and clinical relevance registered by interview with clinicians.	Participants will be followed over 24 weeks.
Secondary	Pharmacological prescription	All the medicines that the patients are taking, start to take, o stop taking during the intervention, registered by interview with clinicians.	Participants will be followed over 24 weeks.
Secondary	Glucose level	Glucose will be analyzed through blood test.	Participants will be followed over 24 weeks.
Secondary	Urea level	Urea will be analyzed through blood test.	Participants will be followed over 24 weeks.
Secondary	Creatinine level	Creatinine will be analyzed through blood test.	Participants will be followed over 24 weeks.
Secondary	Lipid profile analysis	Lipid profile will be analyzed through blood test.	Participants will be followed over 24 weeks.
Secondary	Creatine Kinase concentration	Creatine Kinase (CK) will be analyzed through blood test.	Participants will be followed over 24 weeks.
Secondary	Hemoglobin concentration	Hemoglobin (Hb) will be analyzed through blood test.	Participants will be followed over 24 weeks.
Secondary	Number of lymphocytes	Number of lymphocytes will be analyzed through blood test.	Participants will be followed over 24 weeks.
Secondary	Number of platelets	Number of platelets will be analyzed through blood test.	Participants will be followed over 24 weeks.
Secondary	Number of leukocytes	Number of leukocytes will be analyzed through blood test.	Participants will be followed over 24 weeks.
Secondary	Inflammation	C-Reactive Protein (CRP) will be analyzed trough blood test.	Participants will be followed over 24 weeks.
Secondary	Anti phospholipid antibodies concentration	Autoimmunity Anti phospholipid antibodies parameter will be analyzed through blood test.	Participants will be followed over 24 weeks.
Secondary	Double-stranded anti-DNA antibodies concentration	Autoimmunity Double-stranded anti-DNA antibodies parameter will be analyzed through blood test.	Participants will be followed over 24 weeks.
Secondary	Complement fraction C3 concentration	Autoimmunity Complement fraction C3 parameter will be analyzed through blood test.	Participants will be followed over 24 weeks.
Secondary	Complement fraction C4 concentration	Autoimmunity Complement fraction C4 parameter will be analyzed through blood test.	Participants will be followed over 24 weeks.
Secondary	Cardiorespiratory Fitness	Evaluated by Treadmill Ergometric test.	Participants will be followed over 24 weeks.
Secondary	Functional capacity	Evaluated by the 6-Minute walking test.	Participants will be followed over 24 weeks.
Secondary	Hight	In centimeters; will be evaluated using a measuring tape.	Participants will be followed over 24 weeks.
Secondary	Weight	In kilograms; will be evaluated using an Inbody.	Participants will be followed over 24 weeks.
Secondary	Skeletal Muscle Mass	In kilograms; will be evaluated using an Inbody.	Participants will be followed over 24 weeks.
Secondary	Body Fat Mass	In kilograms; will be evaluated using an Inbody.	Participants will be followed over 24 weeks.
Secondary	Body Mass Index	Weight and height will be combined to report Body Mass Index (BMI) in kg/m^2	Participants will be followed over 24 weeks.
Secondary	Body Fat Index	In %; will be evaluated using an Inbody.	Participants will be followed over 24 weeks.
Secondary	Waist-to-hip ratio in centimeters	In centimeters; waist circumference and hip circumference measures will be combined to calculate waist-to-hip ratio (WHR).	Participants will be followed over 24 weeks.
Secondary	Obesity degree	In %; will be evaluated using an Inbody.	Participants will be followed over 24 weeks.
Secondary	Body Cell Mass	In kilograms; will be evaluated using an Inbody.	Participants will be followed over 24 weeks.
Secondary	Bone Mineral Content	In kilograms; will be evaluated using an Inbody.	Participants will be followed over 24 weeks.
Secondary	Basal Metabolic Rate	In kilocalories; will be evaluated using an Inbody.	Participants will be followed over 24 weeks.
Secondary	Visceral Fat Area	In cm^2; Visceral Fat Area (AVG) will be evaluated using an Inbody.	Participants will be followed over 24 weeks.
Secondary	Bone density	Evaluated by densitometry.	Participants will be followed over 24 weeks.
Secondary	Human Vascular Cell Adhesion Molecule-1 concentration	VCAM-1 endothelial biomarker will be assessed by blood test.	Participants will be followed over 24 weeks.
Secondary	Intercellular Adhesion Molecule-1concentration	ICAM-1 endothelial biomarker will be assessed by blood test.	Participants will be followed over 24 weeks.
Secondary	E-Selectin concentration	E-Selectin endothelial biomarker will be assessed by blood test.	Participants will be followed over 24 weeks.
Secondary	Super Oxide Dismutase concentration	Oxidative Stress SOD biomarker will be assessed by blood test.	Participants will be followed over 24 weeks.
Secondary	Glutathione concentration	Oxidative Stress GSH biomarker will be assessed by blood test.	Participants will be followed over 24 weeks.
Secondary	Total Antioxidant Capacity concentration	Oxidative Stress TAC biomarker will be assessed by blood test.	Participants will be followed over 24 weeks.
Secondary	Thiobarbituric Acid Reactive Substances concentration	Oxidative Stress TBARS biomarker will be assessed by blood test.	Participants will be followed over 24 weeks.
Secondary	Malondialdehyde concentration	Oxidative Stress MDA biomarker will be assessed by blood test.	Participants will be followed over 24 weeks.
Secondary	Advanced Oxidation Protein Products concentration	Oxidative Stress AOPP biomarker will be assessed by blood test.	Participants will be followed over 24 weeks.
Secondary	Total proteins concentration	Oxidative Stress total proteins biomarker, understood as the concentration of proteins in a sample, will be assessed by blood test.	Participants will be followed over 24 weeks.
Secondary	Endothelial Function	Several endothelial function parameters such are arterial pulse wave velocity, AIX index, ABI will be evaluated using arteriography.	Participants will be followed over 24 weeks.
Secondary	miRNA expression profile quantification	Collection of blood samples in Tempus tubes for subsequent analysis of miRNA expression profile by massive sequencing with specific equipment.	Participants will be followed over 24 weeks.
Secondary	Microbiome characteristics analysis	Microbiome study by collecting fecal samples.	Participants will be followed over 24 weeks.