Omega-3 and Exercise in Rheumatoid Arthritis People

July 11, 2023 updated by: Sebastian Jannas-Vela, Instituto de Ciencias de la Salud, Universidad de O'Higgins

Role of Specialized Pro-resolving Mediators on Inflammation, Cardiometabolic Health, Disease Progression, and Quality of Life in Patients With Rheumatoid Arthritis After Omega-3 PUFA Supplementation and Aerobic Exercise Training.

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by autoantibody production and synovial membrane damage. It significantly impairs overall function and quality of life. Consumption of omega-3 (n-3) polyunsaturated fatty acids (PUFAs) and regular aerobic exercise (AEx) training are reported to have positive effects on the progression of RA. However, the mechanisms behind these benefits are still inconclusive. This study aims to investigate the effects of n-3 PUFA supplementation and AEx training on disease progression, cardiometabolic health, and quality of life, and their association with the plasma and synovial fluid levels of specialized pro-resolving mediators (SPMs) in subjects with RA. The study consists of a 16-week intervention period, during which participants will be randomly assigned in a double-blinded manner to one of four groups: placebo control (PLA), PLA+AEx, n-3, or n-3+AEx. The PLA groups will be given a gelatin-filled capsule, while the n-3 groups will be given n-3 PUFAs equivalent to 2.5 g/d of docosahexaenoic acid and 0.5 g/d of eicosapentaenoic acid. The AEx groups will exercise thrice per week on a stationary electronically braked cycle ergometer at 60-70% of their VO2peak for 50-60 minutes. Before and after the intervention, participants will undergo RA-specific and functional measurements, peak aerobic capacity test, and a dietary and physical activity assessment. Venous blood and synovial fluid from the knee joint will be collected. Changes in disease progression, cardiometabolic health, quality of life, and erythrocyte membrane composition to assess n-3 incorporation, SPM levels, inflammatory markers, and gene expression from blood and synovial fluid will be analyzed. The study aims to elucidate the SPMs that regulate the inflammatory gene expression pathways and associate them with improvements in disease progression, cardiometabolic health, and quality of life after n-3 PUFA supplementation and AEx training.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Active, not recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Research hypothesis: N-3 PUFA and AEx will have synergistic effects on disease progression, cardiometabolic health, and quality of life in individuals with RA, and these changes will be associated with SPM production in blood and synovial fluid.

General aim: To investigate the effects of n-3 PUFA supplementation and AEx training on disease progression, cardiometabolic health, and quality of life and their association with the plasma and synovial fluid levels of SPMs in individuals with RA.

Specific aims:

  1. To compare the effects of n-3 PUFA supplementation, AEx training, and the combination of both on disease progression, cardiometabolic health, and quality of life in individuals with RA.
  2. To compare the effects of n-3 PUFA supplementation, AEx, and the combination of both on the plasma and synovial fluid levels of the SPMs in individuals with RA.
  3. To examine the relationship between the plasma levels of the n-3 PUFA derived SPMs with systemic disease progression, cardiometabolic health, and quality of life in individuals with RA

Study design 88 Participants will be recruited from hospitals and private clinics in the central region of Chile, whereas all the interventions regarding AEx will be carried out at the Universidad de O'Higgins and the Hospital Regional de Rancagua. All institutions are in the Región del Libertador Bernardo O'Higgins, Chile. This study consists of a 16-week intervention with n-3 PUFAs and/or aerobic exercise (AEx) training. The subjects will be randomly assigned in a double-blinded manner to one of four groups: placebo control (PLA), PLA+AEx, n-3, or n-3+AEx. A stratified randomized assignment (by block) process will be employed to ensure that the experimental groups are balanced for disease activity, pharmacological treatment, sex, and age. The training sessions will be conducted at the Laboratorio de Ciencias del Ejercicio en el Ciclo Vital (Lab-CERVITAL), Universidad de O'Higgins. The week before intervention the participants will perform RA specific tests (e.g., Disease Activity Score-28) and functional measurements (e.g., handgrip strength), peak aerobic capacity test, a dietary and physical activity assessment, and blood samples will be collected. Subsequently, participants will start their 16-week intervention (PLA, PLA+AEx, n-3, or n-3+AEx). At the end of the intervention the same initial measurements, questionnaires, and assessments will be collected. In a subgroup of participants (n=24 in total or n=6 per group) extraction of synovial fluid will be performed before and after the intervention.

The participants will be supplemented with either 5 capsules per day of Omega UP (Newscience, Chile) equivalent to 2.5 g/d of DHA and 0.5 g/d of EPA or a placebo filled gelatin capsule. The current doses are within the limits recommended by the European Food Safety Authority and have been shown to be safe, to be incorporated into cell membranes, and to produce significant improvements in overall health in individuals with RA. Capsules will be placed into de-identified bottles by people not involved in the study and provided to the participants to ensure double blinding. The exercise intervention will be performed according to the recommendations from the European Alliance of Associations for Rheumatology (EULAR) consisting of aerobic type exercise training three times per week, on non-consecutive days, with a total time of 20-60 minutes. The AEx will be performed on a stationary electronically braked cycle ergometer starting at 40-50% of VO2peak for 20 minutes. The intensity and volume of cycling will then be gradually increased to target at least 60-70% of VO2peak for 50-60 minutes over the final 10 weeks. Heart rate, power output and rating of perceived exertion (RPE) will be monitored during training intervention.

Statistical analysis Results will be expressed as mean ± SD. A two-way ANOVA with repeated measures followed by Fisher's least significant difference post-test for multiple comparisons between groups will be used. Linear regression models will be constructed to examine the association between SPMs and clinical, functional, and health parameters, accounting for participant age, sex, and BMI as covariates. A value of p<0.05 will be considered statistically significant.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
88

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Chile
    • Libertador Bernardo O'Higgins
      • Rancagua, Libertador Bernardo O'Higgins, Chile, 2820000
        • Universidad de O'Higgins

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Patients with rheumatoid arthritis with moderate disease activity as defined by the Disease Activity Score 28 (DAS28) > 2.6 and < 5.1.
  • Participants taking nonsteroidal anti-inflammatory drugs (NSAIDs), glucocorticoids, or disease-modifying anti-rheumatic drugs (DMARDs) will be eligible; however, the dosages of these agents must be constant at least four weeks before, must remain within this limit throughout the study, and prednisone dose should not be higher than 7.5 mg/d

Exclusion Criteria:

  • Individuals diagnosed with gastrointestinal or metabolic diseases, regular alcohol abuse, smokers, and dietary supplement intake (e.g., fish oil capsules) or consumption of fish > 2 times per week.
  • Individuals that perform regular aerobic exercise (> 150 min moderate intensity per week) or have any physical or biomechanical limitations to complete the exercise program
  • Individuals that present blood levels of aspartate aminotransferase, alanine transaminase, or creatinine higher than 1.5 times the maximum normal limit and total bilirubin levels of more than 1.8 mg/dL

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Supportive Care
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Placebo Comparator: Placebo control
The participants will be supplemented with 5 capsules per day of a placebo-filled gelatin capsule.
Dietary supplement: Placebo
The participants will be supplemented with 5 capsules per day of a placebo-filled gelatin capsule for 16 weeks.
Active Comparator: Placebo and aerobic exercise
The participants will be supplemented with 5 capsules per day of a placebo-filled gelatin capsule and will perform aerobic type exercise training three times per week, on non-consecutive days, with a total time of 20-60 minutes per day.
Dietary supplement: Placebo
The participants will be supplemented with 5 capsules per day of a placebo-filled gelatin capsule for 16 weeks.
Dietary supplement: Aerobic exercise
The participants will perform aerobic-type exercise training three times per week, on non-consecutive days, with a total time of 20-60 minutes per day for 16 weeks.
Experimental: Omega-3
The participants will be supplemented with 5 capsules per day of Omega UP (Newscience, Chile) equivalent to 2.5 g/d of DHA and 0.5 g/d of EPA.
Dietary supplement: Omega-3
The participants will be supplemented with 5 capsules per day of Omega UP (Newscience, Chile) equivalent to 2.5 g/d of DHA and 0.5 g/d of EPA for 16 weeks.
Experimental: Omega-3 and aerobic exercise
The participants will be supplemented with 5 capsules per day of Omega UP (Newscience, Chile) equivalent to 2.5 g/d of DHA and 0.5 g/d of EPA and will perform aerobic type exercise training three times per week, on non-consecutive days, with a total time of 20-60 minutes per day.
Dietary supplement: Aerobic exercise
The participants will perform aerobic-type exercise training three times per week, on non-consecutive days, with a total time of 20-60 minutes per day for 16 weeks.
Dietary supplement: Omega-3
The participants will be supplemented with 5 capsules per day of Omega UP (Newscience, Chile) equivalent to 2.5 g/d of DHA and 0.5 g/d of EPA for 16 weeks.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Early morning stiffness
Time Frame: Pre and post intervention (16 weeks)
Duration of morning stiffness in minutes
Pre and post intervention (16 weeks)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Disease activity score-28
Time Frame: Pre and post intervention (16 weeks)
Severity of rheumatoid arthritis using clinical and laboratory data
Pre and post intervention (16 weeks)
Health assessment questionnaire disability index
Time Frame: Pre and post intervention (16 weeks)
Questionnaire that evaluates the functional status of individuals with rheumatoid arthritis
Pre and post intervention (16 weeks)
Quality of life RA
Time Frame: Pre and post intervention (16 weeks)
8-item RA-specific health-related quality of life instrument scale.
Pre and post intervention (16 weeks)
Analgesic use
Time Frame: Pre and post intervention (16 weeks)
Pill counts for paracetamol and NSAIDs
Pre and post intervention (16 weeks)
Timed Up and Go test
Time Frame: Pre and post intervention (16 weeks)
The participant starts in a seated position, stands up upon command, walks 3 meters, turns around, walks back to the chair, and sits down. The time stops when the subject is seated
Pre and post intervention (16 weeks)
Short Physical Performance Battery
Time Frame: Pre and post intervention (16 weeks)
Evaluates lower extremity functional performance using timed measures of standing balance, a 4-meter walk, and five repetitive chair stands
Pre and post intervention (16 weeks)
Handgrip strength
Time Frame: Pre and post intervention (16 weeks)
Measures the maximum isometric strength of the hand and forearm muscles.
Pre and post intervention (16 weeks)
Peak aerobic capacity
Time Frame: Pre and post intervention (16 weeks)
Incremental cycling test to exhaustion using a recumbent cycle ergometer to measure aerobic capacity.
Pre and post intervention (16 weeks)
Dietary assessment
Time Frame: Pre and post intervention (16 weeks)
Dietary record using image-assisted method over three days (two consecutive weekdays and one weekend day)
Pre and post intervention (16 weeks)
Global Physical Activity Questionnaire
Time Frame: Pre and post intervention (16 weeks)
Questionnaire to assess physical activity levels
Pre and post intervention (16 weeks)
Plasma rheumatoid factor
Time Frame: Pre and post intervention (16 weeks)
Plasma rheumatoid factor will be measured via commercial ELISA assay kits.
Pre and post intervention (16 weeks)
Total cholesterol
Time Frame: Pre and post intervention (16 weeks)
Total cholesterol will be measured.
Pre and post intervention (16 weeks)
LDL cholesterol
Time Frame: Pre and post intervention (16 weeks)
LDL cholesterol will be measured.
Pre and post intervention (16 weeks)
HDL cholesterol
Time Frame: Pre and post intervention (16 weeks)
HDL cholesterol will be measured.
Pre and post intervention (16 weeks)
TNF-alfa
Time Frame: Pre and post intervention (16 weeks)
Plasma TNF-alfa will be measured via commercial ELISA assay kits.
Pre and post intervention (16 weeks)
IL-10
Time Frame: Pre and post intervention (16 weeks)
Plasma IL-10 will be measured via commercial ELISA assay kits.
Pre and post intervention (16 weeks)
Gene expression
Time Frame: Pre and post intervention (16 weeks)
Real-time PCR will be carried out to quantify the changes in the expression of genes associated with inflammatory pathways and oxylipin synthesis
Pre and post intervention (16 weeks)
Phospholipid fatty acid composition
Time Frame: Pre and post intervention (16 weeks)
Quantitative extraction of total lipids from erythrocytes, plasma, and synovial fluid will be carried out.
Pre and post intervention (16 weeks)
Oxylipin analyses
Time Frame: Pre and post intervention (16 weeks)
Plasma and synovial fluid samples will be analyzed in duplicate for oxylipins by HPLC/MS/MS.
Pre and post intervention (16 weeks)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Instituto de Ciencias de la Salud, Universidad de O'Higgins

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
University of Manitoba
University of Guelph
University of Chile
Universidad Nacional Andres Bello

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Sebastian Jannas-Vela, PhD, Universidad de O'Higgins

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 15, 2022

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2024

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 1, 2025

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 3, 2023

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 11, 2023

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 14, 2023

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 14, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 11, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 11220333

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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