Disorder Related to Renal Transplantation
Conditions
Keywords
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
Brief summary
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
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.
Interventions
DRUGOmega-3 fatty acids
2,7 g omega-3 fatty acids / day (1 capsule 3 times a day / oral administration)
DRUGPlacebo
Placebo capsules 3 times a day (oral administration)
Sponsors
Aarhus University Hospital
Pronova BioPharma
South-Eastern Norway Regional Health Authority
Aalborg University Hospital
Oslo University Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Glomerular filtration rate | 44 weeks | Iohexol clearance |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Lipids | 44 weeks | Total, LDL and HDL cholesterol, triglycerid and ratios |
| Pulse wave velocity and augmentation index | 44 weeks | — |
| Fibrosis in the renal transplant | 44 weeks | As for inflammation |
| Body composition | 44 weeks | Visceral fat volume and weight, visceral to subcutaneous fat ratio. |
| Bone mineral density | 44 weeks | Regular BMD in the lumbar spine, hips, femur and arms and also selected to trabecular bone. |
| Body mass index | 44 weeks | — |
| Vitamin D levels | 44 weeks | — |
| Fatty acid composition in plasma and renal tissue | 44 weeks | — |
| Tacrolimus pharmacokinetics | 12 weeks | 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 |
| Heart rate variability | 44 weeks | — |
| Flow mediated dilation | 44 weeks | — |
| Blood glucose | 44 weeks | HbA1c and oral glucose tolerance test |
| Blood pressure | 44 weeks | — |
| Proteinuria | 44 weeks | Both ACR and FEPR |
| Inflammation in the renal transplant | 44 weeks | Degree of total inflammation in renal transplant biopsies, scores by PI and rescored by two pathologists. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Adverse events | 44 weeks + 8 weeks | — |
| Adverse reactions | 44 weeks | — |
| Frequency of clinically significant safety laboratory variables | 44 weeks | Especially INR and tacrolimus trough concentrations. Follow-up by local nephrologist plus five Telephone Controls during follow-up. |
| Quality of life | 44 weeks | 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. |
| Food questionnaire | 44 weeks | Two specially designed food questionnaires to obtain data on dietary habits in general and type and amount of fish consumed |
| Comorbidity, concomitant medication and life-style factor interview | 44 weeks | — |
| Incidence of post-transplant complications | 44 weeks + 8 weeks | — |
Countries
Norway
Outcome results
None listed