The Effects of Omega-3 Fatty Acids in Renal Transplantation

Study Overview
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Brief Summary
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Omega-3 fatty acids are provided through dietary intake of fish and seafood. Several dietary supplements containing omega-3 fatty acids are also commercially available. Some studies have described beneficial effects from omega-3 fatty acids, among them are anti-inflammatory, anti-thrombotic, anti-atherosclerotic, anti-arrhythmic, anti-hypertensive and lipid-modulating effects. Other studies have not confirmed these findings. This study will investigate the effects of omega-3 fatty acids on renal function and cardiovascular risk markers in renal transplant recipients.

Detailed Description
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There have been few interventional studies regarding the clinical effect of omega-3 fatty acids in renal transplantation. The aim of this study is to investigate the effects of omega-3 fatty acids on renal function and cardiovascular risk markers in renal transplant recipients. This study is a randomized double blinded placebo controlled interventional study of 132 Norwegian renal transplant recipients. It will investigate, on the one hand, the effect of omega-3 fatty acids on renal function and, on the other, the effect of omega-3 fatty acids on cardiovascular risk markers in renal transplant recipients. 8 weeks after transplantation, if renal function has stabilized, patients with a eGFR>30 will be randomized to receive either 2,7 g eicosapentaenoic plus docosahexaenoic acid (3 capsules of Omacor a 1 g) daily or placebo. Baseline measurements will be performed before they start taking the study medication. The same measurements will performed again1 year after transplantation and the patients stops taking the study medication.

Official Title
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The Effects of n-3 Polyunsaturated Fatty Acids on Renal and Cardiovascular Risk Markers in Renal Transplant Recipients: a Randomized Double Blinded Placebo Controlled Intervention Study.

Conditions
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Disorder Related to Renal Transplantation

Intervention / Treatment
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* Drug: Omega-3 fatty acids
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients over the age of 18 who have received a kidney transplant. Patients with a functioning kidney transplant, defined as eGFR>30 ml/min. Signed informed consent. Exclusion Criteria: Patients participating in clinical trials with other investigational drugs. Patients who received a deceased donor kidney from a donor >75 years. Patients with a history of an allergic reaction or significant sensitivity to the study drug or drugs similar to the study drug.

Ages Eligible for Study
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Minimum Age: 18 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Omega-3 fatty acids<br>2,7 g omega-3 fatty acids / day: Omacor 1 g 1 capsule by mouth 3 times a day for 44 weeks. | Drug: Omega-3 fatty acids<br>* 2,7 g omega-3 fatty acids / day (1 capsule 3 times a day / oral administration)<br>* Other names: Omacor;|
| Placebo Comparator: Placebo<br>Placebo: 1 capsule containing 1 g of olive oil by mouth 3 times a day for 44 weeks. | Drug: Placebo<br>* Placebo capsules 3 times a day (oral administration)<br>* Other names: Olive oil;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glomerular filtration rate | Iohexol clearance | 44 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proteinuria | Both ACR and FEPR | 44 weeks | 
| Inflammation in the renal transplant | Degree of total inflammation in renal transplant biopsies, scores by PI and rescored by two pathologists. | 44 weeks | 
| Fibrosis in the renal transplant | As for inflammation | 44 weeks | 
| Blood pressure |  | 44 weeks | 
| Heart rate variability |  | 44 weeks | 
| Flow mediated dilation |  | 44 weeks | 
| Pulse wave velocity and augmentation index |  | 44 weeks | 
| Blood glucose | HbA1c and oral glucose tolerance test | 44 weeks | 
| Lipids | Total, LDL and HDL cholesterol, triglycerid and ratios | 44 weeks | 
| Body composition | Visceral fat volume and weight, visceral to subcutaneous fat ratio. | 44 weeks | 
| Bone mineral density | Regular BMD in the lumbar spine, hips, femur and arms and also selected to trabecular bone. | 44 weeks | 
| Body mass index |  | 44 weeks | 
| Vitamin D levels |  | 44 weeks | 
| Fatty acid composition in plasma and renal tissue |  | 44 weeks | 
| Tacrolimus pharmacokinetics | Substudy of 15 patients, where we study tacrolimus trough levels, Tmax and AUC at the end of the ORENTRA trial, after a minimum of 4 weeks wash-out and again after 4 weeks of 2.7 g omega-3 fatty acid supplementation | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Renal transplantation, Interventional study, Glomerular filtration rate, Renal function, Proteinuria, Cardiovascular risk markers, Blood pressure, Flow mediated vasodilation, Heart rate variability, Pulse wave velocity, Lipids, Blood glucose, Bone mineral density, Body composition, Fat distribution, Body mass index, Fatty acid composition, Tacrolimus pharmacokinetics, Omega-3 fatty acids, Marine n-3 fatty acids, Fatty acids, Gas chromatography, Interstitial fibrosis, Inflammation