Effectiveness of Multigrain Supplementation Among the Rheumatoid Arthritis Patients

Study Overview
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Brief Summary
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The objective of this study is to evaluate the effect of high fiber multigrain supplementation on the level of clinical disease severity measures, blood inflammatory molecules, and nutritional status changes in RA patients.

Detailed Description
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Rheumatoid Arthritis (RA) is a chronic inflammatory, autoimmune rheumatic disease, resulting in progressive joint inflammation and destruction. At present, there is no known cure for this disease. As a consequence of the potential side effects, many RA patients turn to other alternative remedies such as specialised diets and/or dietary supplements in a bid to relieve their symptoms. Therefore, the current study aims to examine the effectiveness of high fiber multigrain supplementation on the level of clinical disease severity measures, blood inflammatory molecules, together with the nutritional status changes in RA patients, as compare with conventional drug treatments.

Official Title
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Effectiveness of High Fiber Multigrain Supplementation Among the Rheumatoid Arthritis Patients: A Randomized, Open Label Trial

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Dietary Supplement: Multigrain powder (S)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: RA patients according to the American College of Rheumatology (ACR) Moderate (DAS 28 = 3.2 - 5.1) and severe (DAS 28 > 5.1) RA manifestation Chronological age: 21 years and above Stable RA patients who are receiving NSAIDs, glucocorticoids/DMARDs (for example leflunomide, methotrexate, sulfasalazine and hydroxychloroquine) for at least 3 months prior to entering the study Not taking antioxidant/antiinflammatory supplements (Example of antioxidant: vitamin C, vitamin E, grape seed extract, garlic capsule, ginkgo biloba) (Example of anti-inflammatory supplement: fish oil, curcumin extract, ginger extract, spirulina) Exclusion Criteria: Having liver (chronic liver failure, cirrhosis, all types of hepatitis), kidney (chronic kidney disease, haemodialysis) or haematological (anaemia, thalassemia, haemophilia) disorders Active gastric/duodenal ulcer Psychiatric disease/mental retardation (bipolar disorder, depression, schizophrenia) Cancer (all types), Diabetes Mellitus (Type I and II), uncontrolled hypertension (BP at 140/90 mmHg for the past 3 months), and endocrine disorders (Cushing's disease, gigantism and hyperthyroidism). Alcohol and drug abuse (self-mentioned or as recorded in the medical card) Other autoimmune/inflammatory diseases (systemic lupus erythematosus, multiple sclerosis, gout, psoriasis, chronic inflammatory demyelinating polyneuropathy) Pregnancy/lactation Hormone replacement therapy (for at least 3 months prior to entering the study) Herbal remedies (any parts from the plants such as flowers, rhizome, seeds, roots, leaves, fruits, stems) Vegetarian patient (pure vegan) Gluten intolerance Participations from another supplementary program

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Multigrain powder (S)<br>Oral high fiber multigrain supplements | Dietary Supplement: Multigrain powder (S)<br>* A twice daily high fiber multigrain powder supplementation for 12 weeks<br>|
| No Intervention: Standard care (C)<br>Standard care without oral high fiber multigrain supplements | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease Activity Score-28 (DAS-28) | The DAS-28 is a system developed and validated by the EULAR (European League Against Rheumatism) to measure the progress and improvement of Rheumatoid Arthritis. DAS-28 values range from 2.0 to 10.0, while higher values mean a higher disease activity. The complex mathematical calculation is calculated by incorporating the value of erythrocyte sedimentation rate (ESR) and Visual Analog Scale (VAS). ESR (mm/hr) determines the severity of inflammatory response and monitor the effect of treatment. VAS is an indicator for pain intensity and patient global health, and the following cut points have been recommended: no pain (0-4 mm), mild pain (5-44 mm), moderate pain (45-74 mm), and severe pain (75- 100 mm). DAS-28 = 0.56 * sqrt(tender28) + 0.28 * sqrt(swollen28) + 0.70 * ln(ESR) + 0.014 * GH The scale categorises RA manifestations as mild (DAS-28: <3.2), moderate (DAS-28: 3.2-5.1) or severe (DAS-28: >5.1) | Baseline and 12 weeks | 
| Health Assessment Questionnaire-Disability Index (HAQ-DI) | The HAQ-DI is used to measure physical functionality. The HAQ-DI is usually analyzed by calculating scores. The single scales range from 0 (no difficulty) to 3 (unable to do). The total score ranges from 0-24, and higher score indicates severe disability. | Baseline and 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Blood glucose level | Blood glucose is measured in mmol/L | Baseline and 12 weeks | 
| Glycated hemoglobin (HbA1c) | Glycated hemoglobin (HbA1c) is measured in % | Baseline and 12 weeks | 
| White blood cell (WBC) count | White blood cell (WBC) differential count is measured in x10^9/L | Baseline and 12 weeks | 
| Red blood cell (RBC) count | Red blood cell (RBC) count is measured in x10^12/L | Baseline and 12 weeks | 
| Hemoglobin (Hb) | Hemoglobin (Hb) is measured in g/dl | Baseline and 12 weeks | 
| Hematocrit (Hct) | Hematocrit (Hct) is measured in % | Baseline and 12 weeks | 
| Mean corpuscular volume (MCV) | Mean corpuscular volume (MCV) is measured in l/cell | Baseline and 12 weeks | 
| Mean corpuscular hemoglobin (MCH) | Mean corpuscular hemoglobin (MCH) is measured in g/cell | Baseline and 12 weeks | 
| Platelet (PLT) count | Platelet (PLT) count is measured in x10^9/L | Baseline and 12 weeks | 
| Total cholesterol | Total cholesterol is measured in mmol/L | Baseline and 12 weeks | 
| Low density lipoprotein (LDL)-cholesterol | Low density lipoprotein (LDL)-cholesterol is measured in mmol/L | Baseline and 12 weeks | 
| High density lipoprotein (HDL)-cholesterol | High density lipoprotein (HDL)-cholesterol is measured in mmol/L | Baseline and 12 weeks | 
| Triglyceride (Tg) | Triglyceride (Tg) is measured in mmol/L | Baseline and 12 weeks | 
| Sodium level | Sodium level is measured in mmol/L | Baseline and 12 weeks | 
| Potassium level | Potassium level is measured in mmol/L | Baseline and 12 weeks | 
| Chloride level | Chloride level is measured in mmol/L | Baseline and 12 weeks | 
| Blood urea nitrogen (BUN) level | Blood urea nitrogen (BUN) level is measured in mmol/L | Baseline and 12 weeks | 
| Serum creatinine level | Serum creatinine level is measured in umol/L | Baseline and 12 weeks | 
| Calcium level | Calcium level is measured in mmol/L | Baseline and 12 weeks | 
| Uric acid level | Uric acid level is measured in umol/L | Baseline and 12 weeks | 
| Phosphorus level | Phosphorus level is measured in mmol/L | Baseline and 12 weeks | 
| Albumin | Albumin is measured in g/L | Baseline and 12 weeks | 
| Total protein | Total protein is measured in g/L | Baseline and 12 weeks | 
| Total bilirubin | Total bilirubin is measured in umol/L | Baseline and 12 weeks | 
| Alkaline phosphatase (ALP) | Alkaline phosphatase (ALP) is measured in U/L | Baseline and 12 weeks | 
| Alanine transaminase (ALT) | Alanine transaminase (ALT) is measured in U/L | Baseline and 12 weeks | 
| Aspartate transaminase (AST) | Aspartate transaminase (AST) is measured in U/L | Baseline and 12 weeks | 
| Serum interleukin-6 (IL-6) | Interleukin-6 (IL-6) is a pleiotropic cytokine with a pivotal role in the pathophysiology of rheumatoid arthritis. The level correlates with the disease activity and joint destruction. Serum IL-6 is measured in pg/ml | Baseline and 12 weeks | 
| Serum interleukin 1β (IL-1β) | Interleukin 1β is among the most important proinﬂammatory cytokines in rheumatoid arthritis. Serum IL-1β is measured in pg/ml | Baseline and 12 weeks | 
| Tumor necrosis factor-alpha (TNF-α) | Tumor necrosis factor-alpha (TNF-α) is a proinflammatory cytokine that plays a pivotal role in regulating the inflammatory response in rheumatoid arthritis. Serum IL-1β is measured in pg/ml | Baseline and 12 weeks | 
| High sensitivity-C-Reactive Protein (hs-CRP) | High sensitivity-C-Reactive Protein (hs-CRP) is a disease activity marker in rheumatoid arthritis. Serum hs-CRP is measured in pg/ml | Baseline and 12 weeks | 
| Serum matrix metalloproteinase-3 (MMP-3) | MMP-3 is increased in rheumatoid arthritis, and has been proposed as a marker of joint damage and systemic inflammation. Serum MMP-3 is measured in ng/ml | Baseline and 12 weeks | 
| Body mass index (BMI) | Body weight (in kilograms) and standing height (in meters) will be measured to indicate nutritional status. The weight and height will be combined to report BMI in kg/m^2 | 12 weeks | 
| Waist hip ratio | Waist (in cm) and hip (in cm) circumferences will be measured to indicate obesity. This is calculated as waist measurement divided by hip measurement. | 12 weeks | 
| Body fat | Body fat is measured in % | Baseline and 12 weeks | 
| Fat mass | Fat mass is measured in % | Baseline and 12 weeks | 
| Fat free mass | Fat free mass is measured in % | Baseline and 12 weeks | 
| Total body water | Total body water is measured in L | Baseline and 12 weeks | 
| Estimated average required energy | Estimated average required energy is measured in kcal | Baseline and 12 weeks | 
| Tolerability assessment | The participant's complaints of gastrointestinal discomfort upon supplement consumption such as heart burn, diarrhea, nausea, vomiting and headache will be recorded, and it will be reported as the frequency (n) of discomfort episodes. | At 4 weeks, 8 weeks and 12 weeks | 
| Compliance assessment | Remaining sachet counting: The remaining sachet/unfinished sachet will be counted, and compliance will be reported as %. | At 4 weeks, 8 weeks and 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Rheumatoid Arthritis, Fiber, Multigrain