The Effects of Omega-3 Fatty Acids in Renal Transplantation (ORENTRA)

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.

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.

Study Overview

• Status: Completed
• Conditions: Disorder Related to Renal Transplantation
• Intervention / Treatment: Drug: Omega-3 fatty acids; Drug: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 132
• Phase: Phase 4

Contacts and Locations

Study Locations

• Norway
  • Oslo, Norway, 0027
    • Oslo University Hospital, Rikshospitalet
  • * Other
    • Oslo, * Other, Norway, 0424
      • Oslo University Hospital Rikshospitalet

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of post-transplant complications		44 weeks + 8 weeks
Adverse events		44 weeks + 8 weeks
Adverse reactions		44 weeks
Frequency of clinically significant safety laboratory variables	Especially INR and tacrolimus trough concentrations. Follow-up by local nephrologist plus five Telephone Controls during follow-up.	44 weeks
Quality of life	The participants fill out SF-36 at baseline and the 1 year post transplant control for both safety reasons and measurement of differences between the groups with regards to quality of life.	44 weeks
Food questionnaire	Two specially designed food questionnaires to obtain data on dietary habits in general and type and amount of fish consumed	44 weeks
Comorbidity, concomitant medication and life-style factor interview		44 weeks

Collaborators and Investigators

• Sponsor: Oslo University Hospital
• Collaborators: Aarhus University Hospital; Aalborg University Hospital; South-Eastern Norway Regional Health Authority; Pronova BioPharma
• Investigators: Principal Investigator: Ivar A Eide, MD, Oslo University Hospital

Publications and helpful links

General Publications

• Chan J, Eide IA, Tannaes TM, Waldum-Grevbo B, Jenssen T, Svensson M. Marine n-3 Polyunsaturated Fatty Acids and Cellular Senescence Markers in Incident Kidney Transplant Recipients: The Omega-3 Fatty Acids in Renal Transplantation (ORENTRA) Randomized Clinical Trial. Kidney Med. 2021 Oct 4;3(6):1041-1049. doi: 10.1016/j.xkme.2021.07.010. eCollection 2021 Nov-Dec.
• Eide IA, Reinholt FP, Jenssen T, Hartmann A, Schmidt EB, Asberg A, Bergan S, Brabrand K, Svensson M. Effects of marine n-3 fatty acid supplementation in renal transplantation: A randomized controlled trial. Am J Transplant. 2019 Mar;19(3):790-800. doi: 10.1111/ajt.15080. Epub 2018 Sep 22.

Study record dates

Study Major Dates

• Study Start: November 1, 2013
• Primary Completion (Actual): December 1, 2015
• Study Completion (Actual): December 1, 2015

Study Registration Dates

• First Submitted: December 4, 2012
• First Submitted That Met QC Criteria: December 4, 2012
• First Posted (Estimate): December 6, 2012

Study Record Updates

• Last Update Posted (Estimate): December 8, 2015
• Last Update Submitted That Met QC Criteria: December 6, 2015
• Last Verified: December 1, 2015

More Information

Terms related to this study

• Keywords: Inflammation; Body composition; Omega-3 fatty acids; Blood pressure; Lipids; Glomerular filtration rate; Proteinuria; Bone mineral density; Heart rate variability; Body mass index; Pulse wave velocity; Fatty acids; Renal function; Renal transplantation; Blood glucose; Cardiovascular risk markers; Fatty acid composition; Interventional study; Flow mediated vasodilation; Interstitial fibrosis; Fat distribution; Tacrolimus pharmacokinetics; Marine n-3 fatty acids; Gas chromatography
• Other Study ID Numbers: 2012/1419 (Other Identifier: Norway: REK); 2012-004992-37 (EudraCT Number); 2012033 (Other Grant/Funding Number: Norway: Regional Health Authority)