Mussels, Inflammation and Rheumatoid Arthritis (MIRA)

Study Overview
=================
Brief Summary
-----------------
Rheumatoid arthritis (RA) is a chronic disease that affects  1% of the population. A large proportion of patients with established disease have persistent high disease activity in spite of existing effective pharmacological treatment. Improved treatment is thus urgently needed, including alternative treatments in addition to optimal pharmacological therapy. The main purpose of this study is to investigate if a high intake of blue mussel (Mytilus Edulis) could decrease inflammation and disease activity in patients with established RA. A secondary goal is to identify novel biomarkers for blue mussel intake and metabolic responses to this diet, using a metabolomics approach with high sensitivity and specificity. A third goal is to look at genetic polymorphisms in relation to long chain polyunsaturated fatty acids (LCPUFA) and inflammatory markers.

Detailed Description
-----------------
Rheumatoid arthritis (RA) is a chronic disease that affects  1% of the population. A large proportion of patients with established disease have persistent high disease activity in spite of existing effective pharmacological treatment. Improved treatment is thus urgently needed, including alternative treatments in addition to optimal pharmacological therapy. The main purpose of this study is to investigate if a high intake of blue mussel (Mytilus Edulis) could decrease inflammation and disease activity in patients with established RA. A secondary goal is to identify novel biomarkers for blue mussel intake and metabolic responses to this diet, using a metabolomics approach with high sensitivity and specificity. A third goal is to look at genetic polymorphisms in relation to LCPUFA and inflammatory markers. Diet and lifestyle are associated with chronic diseases such as cardiovascular diseases, cancer and diabetes. Here, evidence based dietary treatment guidelines are available. In contrast, for inflammatory diseases such as RA no dietary guidelines exist, reflecting the ambiguous evidence base. Many dietary components are related to the human immune system or to inflammation. Some are co-factors in immune- or inflammatory response, such as zinc. Others are antioxidants, eg selenium, vitamins E and C. RA has been associated with low serum concentrations of zinc, selenium, vitamins D and B6 although some of this may reflect inflammatory response. Dietary effects on RA symptoms have been reported for long chain fatty acids from fish and probiotics have shown to improve function in RA patients. As prebiotics reduce inflammation in other conditions, it may have positive effects also on RA. Most research on antioxidants has focused on single nutrients but a few dietary trials also have been conducted with mixed results. In sum, high-quality studies evaluating the effect of a combination of food items with indicative effects on RA are needed. Blue mussels are rich in vitamins (B2 and B12) and minerals (iron, selenium and zinc) and contain the LCPUFA eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA).

Official Title
-----------------
Mussels, Inflammation and Rheumatoid Arthritis (MIRA)

Conditions
-----------------
Rheumatoid Arthritis

Intervention / Treatment
-----------------
* Other: Blue mussel diet
* Other: Meat/Control diet


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: BMI 18-40 kg/m2, disease duration >2 years, DAS28 >3.0 Exclusion Criteria: other Life-threatening disease, pregnant, lactating, food intolerant or allergic to food included in the study.

Ages Eligible for Study
-----------------
Minimum Age: 25 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Blue mussel diet<br>5 meals a week including blue mussels | Other: Blue mussel diet<br>* 5 meals a week containing blue mussels<br>|
| Active Comparator: Meat/control diet<br>5 meals a week including meat | Other: Meat/Control diet<br>* 5 meals a week containing meat<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| difference between disease activity score 28 (DAS28) after the diets | Measured clinically | after 11 week intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| difference in inflammatory markers/cytokines (IL-1beta, IL-6, Tumor Necrosis Factor-alfa, IL-10) after the diets | measured in blood | after 11 week intervention | 
| Difference in Quality of life and health by SF36, EQ5D och HAQ after the diets | Measured by validated instruments (SF36, EQ5D och HAQ) | after 11 week intervention | 
| Differences and changes in metabolites after the two diets | Metabolomics Nuclear magnetic resonance (NMR) analysis of serum and urin samples. | after 11 week intervention |