- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05945693
Omega-3 and Exercise in Rheumatoid Arthritis People
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.
Study Overview
Status
Conditions
Intervention / Treatment
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:
- 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.
- 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.
- 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
Enrollment (Estimated)
Phase
- Not Applicable
Contacts and Locations
Study Locations
-
-
Libertador Bernardo O'Higgins
-
Rancagua, Libertador Bernardo O'Higgins, Chile, 2820000
- Universidad de O'Higgins
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
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
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 |
Intervention / Treatment |
---|---|
Placebo Comparator: Placebo control
The participants will be supplemented with 5 capsules per day of a placebo-filled gelatin capsule.
|
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.
|
The participants will be supplemented with 5 capsules per day of a placebo-filled gelatin capsule for 16 weeks.
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.
|
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.
|
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.
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
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
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
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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)
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Analgesic use
Time Frame: Pre and post intervention (16 weeks)
|
Pill counts for paracetamol and NSAIDs
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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
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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.
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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)
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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)
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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)
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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)
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Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Sebastian Jannas-Vela, PhD, Universidad de O'Higgins
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 11220333
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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