Go Fish: Omega-3 Fatty Acid Supplementation in Diabetes-Related Kidney Disease

Study Overview
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Brief Summary
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In this application the investigators describe plans for a randomized controlled cross-over trial to determine the effects of omega-3 fatty acid supplementation on urine protein excretion in 30 adults with diabetes (NIDDM) and kidney disease defined by the presence of proteinuria.

Detailed Description
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Diabetes is the most common cause of end-stage kidney disease in the United States. Half of patients with diabetes develop kidney disease. The benefits of omega-3 fatty acids have been shown in animal models of kidney injury. Mechanistic studies of omega-3 fatty acid supplements support biological plausibility: omega-3 supplements have been shown to improve vascular reactivity, lower oxidative stress, reduce inflammation, and have beneficial effects on the metabolism of eicosanoids favoring synthesis of vasodilatory prostaglandins and thromboxanes. However, in spite of overwhelming evidence for a potential benefit of dietary omega-3 fatty acids at preventing or slowing progression of kidney disease for adults with NIDDM, clinical trials providing evidence to support recommendations of supplementation are lacking. The current recommendation for omega-3 intake for adults, one gram/day of DHA+EPA, is based on evidence for cardiovascular disease risk (CVD) reduction. Whether omega-3 fatty acid prevents or slows progression of diabetic kidney disease, whether the current recommended dose is adequate to modify disease, or whether a higher dose should be recommended, needs to be determined. In this setting, we propose to conduct a randomized placebo-controlled cross-over clinical trial to determine the effects of a daily dose of omega-3 fatty acid supplementation (4.0 g/day) compared with placebo on urine protein excretion and biomarkers of kidney injury and function in adults with diabetes and proteinuria.

Official Title
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Go FishOmega-3 Fatty Acid Supplementation in Diabetic Kidney Disease

Conditions
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Diabetes

Intervention / Treatment
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* Dietary Supplement: Lovaza (fish oil)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants have a diagnosis of diabetes (either oral medication or diet controlled) Have an average systolic blood pressure (SBP) <150 and diastolic blood pressure (DBP) <90 mmHg Have quantified proteinuria -- urine albumin/creatinine ratio of > 17 mg/g (men) and >25 mg/g (women) (i.e. at least microalbuminuria). Participants must be on stable doses of antihypertensive, hypoglycemic, and lipid lowering medications for a minimum of two months prior to randomization. Participants must agree to stay on stable doses of diabetes, antihypertensive and lipid medication for the duration of the study. Exclusion Criteria: Major exclusion criteria will be poorly controlled diabetes (Hemoglobin A1c >9%) Use of insulin Use of fish oil supplements or are unwilling to stop fish oil supplements one month prior to randomization and refrain from the supplements during the study Stage 4 or stage 5 CKD or a screening urine protein/creatinine ratio of >2.5.

Ages Eligible for Study
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Minimum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lovaza<br>4 grams per day | Dietary Supplement: Lovaza (fish oil)<br>* 4 grams per day<br>* Other names: omega three fattay acids (generic);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| urine protein excretion | Primary Specific Aim To determine the effects of omega-3 fatty acid supplementation on urine protein excretion and surrogate markers of kidney injury including: serum beta-microglobulin and cystatin C (biomarkers of GFR) and urine neutrophil gelatinase-associated lipocain (NGAL a.k.a. lipocalin-2), kidney injury molecule-1 (KIM-1), and interleukin-18 (IL-18) (biomarkers of tubular reabsorption impairment and inflammation). | end of 2 six week periods (crossover) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Biomarkers of oxidation and inflammation | To determine the effects of omega-3 supplements on markers of oxidations (urine isoprostanes) and inflammation (serum C-reactive protein (hsCRP), RBC fatty acids . | end of 2 six week periods (crossover) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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randomized trial, omega three fatty acids