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.
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 88
- 试验地点
- 2
- 主要终点
- Early morning stiffness
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Supportive Care
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
The masking process will ensure that both the participants and the investigators involved in the study remain unaware of the treatment assignments throughout the entire duration of the study. A unique identification code will be assigned to each participant upon enrollment, which conceals their treatment allocation. The allocation sequence will be generated by a person not directly involved in the study. The capsules in the experimental intervention and the control treatment, will be packaged identically to maintain visual similarity. The packaging materials and labeling will be designed to be indistinguishable between the two groups. In addition, all outcome assessments and data collection procedures will be performed by personnel who are blinded to the treatments.
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with rheumatoid arthritis with moderate disease activity as defined by the Disease Activity Score 28 (DAS28) > 2.6 and < 5.
- •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
排除标准
- •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
结局指标
主要结局
Early morning stiffness
时间窗: Pre and post intervention (16 weeks)
Duration of morning stiffness in minutes
次要结局
- Disease activity score-28(Pre and post intervention (16 weeks))
- Short Physical Performance Battery(Pre and post intervention (16 weeks))
- Quality of life RA(Pre and post intervention (16 weeks))
- Timed Up and Go test(Pre and post intervention (16 weeks))
- Peak aerobic capacity(Pre and post intervention (16 weeks))
- Health assessment questionnaire disability index(Pre and post intervention (16 weeks))
- Analgesic use(Pre and post intervention (16 weeks))
- Handgrip strength(Pre and post intervention (16 weeks))
- Dietary assessment(Pre and post intervention (16 weeks))
- Total cholesterol(Pre and post intervention (16 weeks))
- HDL cholesterol(Pre and post intervention (16 weeks))
- TNF-alfa(Pre and post intervention (16 weeks))
- Gene expression(Pre and post intervention (16 weeks))
- Plasma rheumatoid factor(Pre and post intervention (16 weeks))
- IL-10(Pre and post intervention (16 weeks))
- Global Physical Activity Questionnaire(Pre and post intervention (16 weeks))
- LDL cholesterol(Pre and post intervention (16 weeks))
- Phospholipid fatty acid composition(Pre and post intervention (16 weeks))
- Oxylipin analyses(Pre and post intervention (16 weeks))
研究者
Sebastian Jannas-Vela
Assistant Professor
Instituto de Ciencias de la Salud, Universidad de O'Higgins