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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Kidney Transplantation
• Intervention / Treatment: Drug: Omacor; Drug: Placebo Oral Capsule

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 174
• Phase: Phase 3

Contacts and Locations

Study Locations

• Norway
  • Bergen, Norway, 5021
    • Haukeland University Hospital
  • Oslo, Norway, 0450
    • Ullevaal University Hospital
  • Tromsø, Norway
    • University Hospital of North Norway
  • Akershus
    • Lørenskog, Akershus, Norway, 1478
      • Akershus University Hospital
  • Buskerud
    • Drammen, Buskerud, Norway, 3004
      • Drammen Hospital
  • Hedmark
    • Elverum, Hedmark, Norway, 2409
      • Elverum Hospital

Participation Criteria

Eligibility Criteria

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

Description

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.

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
Experimental: Marine n-3 PUFAs; 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; As described in "Arms".; Other Names: DHA; EPA; Omega-3 fatty acids; Marine n-3 polyunsaturated fatty acids
Placebo Comparator: Placebo; Corresponding placebo oral capsules with olive oil, three capsules daily.	Drug: Placebo Oral Capsule; As described in "Arms".; Other Names: Olive oil

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events	Incl. number of graft rejections and losses, cardiovascular events and deaths	156 weeks
Adverse reactions		156 weeks

Collaborators and Investigators

• Sponsor: Joe Chan
• Collaborators: University of Oslo; Ullevaal University Hospital; University Hospital of North Norway; Haukeland University Hospital; Rikshospitalet University Hospital; Aalborg University Hospital; South-Eastern Norway Regional Health Authority; Drammen sykehus; Pronova BioPharma; Elverum Hospital
• Investigators: Study Director: My Svensson, MD, PhD, University Hospital, Akershus; Study Chair: Ivar Anders Eide, MD, PhD, University Hospital, Akershus; Study Chair: Branimir Draganov, MD, Ullevaal University Hospital; Principal Investigator: Joe Chan, MD, University Hospital, Akershus; Principal Investigator: Morten Reier-Nilsen, MD, Drammen sykehus; Principal Investigator: Tone Granseth, MD, Elverum Hospital; Principal Investigator: Nanna von der Lippe, MD, PhD, Ullevaal University Hospital; Principal Investigator: Bård Endre Waldum-Grevbo, MD, PhD, Ullevaal University Hospital; Principal Investigator: Per Olav Rui, MD, Haukeland University Hospital; Principal Investigator: Toralf Melsom, MD, PhD, University Hospital of North Norway; Principal Investigator: Renathe Rismo, MD, PhD, University Hospital of North Norway

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2017
• Primary Completion (Estimated): August 31, 2025
• Study Completion (Estimated): August 31, 2025

Study Registration Dates

• First Submitted: January 10, 2017
• First Submitted That Met QC Criteria: January 10, 2017
• First Posted (Estimated): January 11, 2017

Study Record Updates

• Last Update Posted (Estimated): December 6, 2023
• Last Update Submitted That Met QC Criteria: December 5, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Inflammation; Omega-3 fatty acids; Blood pressure; Lipids; Glomerular filtration rate; Proteinuria; Kidney transplantation; Heart rate variability; Body mass index; Fatty acids; Renal function; Renal transplantation; Blood glucose; Kidney biopsy; Fatty acid composition; Interventional study; Interstitial fibrosis; Marine n-3 fatty acids; Gas chromatography; Allograft function; Allograft biopsy
• Other Study ID Numbers: 2016/1652 (REK); 2016-003537-18 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No