The Long-term Effect of Marine Omega-3 Fatty Acid Supplementation in Renal Transplantation

Study Overview
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Brief Summary
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This is a long-term intervention study on the effects of marine n-3 PUFAs in renal transplantation. Our hypothesis is that patients treated with marine n-3 PUFA supplementation will have less decline in kidney transplant function compared to patients treated with placebo.

Detailed Description
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The study is designed as a randomized, double blind, placebo controlled, multi-center trial of 174 renal transplant recipients. Patients will be randomized to oral supplementation of marine n-3 PUFA 2.5 g / day or control in a 1:1 fashion. The primary endpoint is change in estimated glomerular filtration rate after 156 weeks in the treatment group compared with the control group. Secondary endpoints include the following variables: proteinuria, plasma inflammatory biomarkers, blood pressure, resting heart rate, fasting serum glucose / HbA1c, lipid and lipoprotein concentrations, number of graft rejections and graft losses, and number of cardiovascular events and deaths. Patients from Akershus University Hospital will also participate in a sub-study, where renal graft biopsies will be performed to assess the degree of fibrosis and chronic allograft damage index (CADI) and markers of fibrosis.

Official Title
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The Long-term Effect of Marine n-3 Polyunsaturated Fatty Acid Supplementation on Glomerular Filtration Rate and Development of Fibrosis in the Renal Allograft: a Randomized Double Blind Placebo Controlled Intervention Study

Conditions
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Kidney Transplantation

Intervention / Treatment
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* Drug: Omacor
* Drug: Placebo Oral Capsule


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Renal transplant recipients over 18 years of age. Stable renal graft function, defined as eGFR >30 ml/min at the last 2 visits. 6-60 months post-transplantation at randomization. Signed informed consent. Exclusion Criteria: Women of childbearing potential who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for up to 4 weeks after the last dose of study drug. Women who are pregnant or breastfeeding. Patients who participate in a clinical trial with other investigational drugs. Patients with a history of an allergic reaction or significant sensitivity to fish, seafood and the study drug Omacor or drugs or dietary supplements similar to the study drug. Any reason why, in the opinion of the Principal Investigator, the patient should not participate - E.g. history of repeated non-adherence to prescribed treatment, repeated non-attendance to clinic visits, cognitive impairment that prevents understanding the nature of this study, etc.

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 |
| --- | --- |
| Experimental: Marine n-3 PUFAs<br>3 capsules of Omacor 1000 mg daily, corresponding to a dose of 2.5 g / day of marine n-3 PUFAs (EPA plus DHA). | Drug: Omacor<br>* As described in Arms.<br>* Other names: Marine n-3 polyunsaturated fatty acids;|
| Placebo Comparator: Placebo<br>Corresponding placebo oral capsules with olive oil, three capsules daily. | Drug: Placebo Oral Capsule<br>* As described in Arms.<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 | Estimated by CKD-EPI equation | 156 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proteinuria | ACR and FE-protein | 156 weeks | 
| Plasma fatty acid levels | measured by gas chromatography | 156 weeks | 
| Plasma inflammatory biomarkers |  | 156 weeks | 
| Blood pressure |  | 156 weeks | 
| Resting heart rate |  | 156 weeks | 
| Fasting serum glucose / HbA1c |  | 156 weeks | 
| Lipid and lipoprotein concentrations |  | 156 weeks | 
| Body mass index |  | 156 weeks | 
| Heart rate variability | Sub-study, participants from Akershus University Hospital only | 156 weeks | 
| The degree of fibrosis and chronic allograft damage index (CADI) in renal cortical tissue | Sub-study, participants from Akershus University Hospital only | 156 weeks | 
| Markers of fibrosis in renal cortical tissue | Sub-study, participants from Akershus University Hospital only | 156 weeks | 
| Fatty acid levels in renal cortical tissue | Sub-study, participants from Akershus University Hospital only | 156 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Kidney transplantation, Renal transplantation, Omega-3 fatty acids, Marine n-3 fatty acids, Fatty acids, Inflammation, Interstitial fibrosis, Glomerular filtration rate, Renal function, Allograft function, Proteinuria, Blood pressure, Heart rate variability, Lipids, Blood glucose, Body mass index, Fatty acid composition, Gas chromatography, Interventional study, Allograft biopsy, Kidney biopsy