Effects of Marine n-3 Fatty Acids on Heart Rate Variability and Arrhythmias in Patients Receiving Chronic Dialysis

Study Overview
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Brief Summary
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Background: End Stage Renal Disease (ESRD) patients have an extremely high mortality and the leading cause of death is cardiovascular disease which accounts for 50% of all deaths. It is estimated that about one third is due to arrhythmias. Previous studies reveal a higher risk of various arrhythmias in dialysis patients but the prevalence is uncertain. Atrial fibrillation is the most common arrhythmia among patients with ESRD. The arrhythmia is often asymptomatic, but the risk of stroke increases dramatically and the annual mortality doubles. Autonomic cardiac dysfunction is often seen in patients with ESRD, and this is expressed by attenuated Heart Rate Variability (HRV) which is a measure of the variation in the time interval between heart beats. Attenuated 24 hours HRV is associated with an increased risk of sudden cardiac death in the general population and among patients with ESRD. N-3 polyunsaturated fatty acids (PUFAs) in fish or fish oil supplements have been shown to increase HRV and reduce the risk of various ventricular and supraventricular arrhythmias in some but not all studies, but this effect has only been sparsely investigated in the high risk patients with ESRD, who has a very low intake of n-3 PUFAs. Objective: The purpose of this study is to investigate the effects of n-3 PUFA supplementation on HRV and arrhythmias in dialysis patients. Hypothesis: n-3 PUFA supplementation increases 24 hours HRV in dialysis patients. n-3 PUFA supplementation reduces the level of Supraventricular tachycardia, premature atrial complexes (PACs) and premature ventricular complexes (PVCs) in chronic dialysis patients. Design: Randomized double-blind, placebo controlled trial Study participants: 140 dialysis patients at Aalborg University Hospital and Vendsyssel Hospital, Hjørring in Denmark. Inclusion time: Summer 2014 to Fall 2015 Methods: The patients are allocated to 3 months treatment with supplements of 2 g n-3 PUFAs or placebo (olive oil). The following data are registered at baseline and after 3 months treatment: Demographics and medical history, Standard ECG-12, blood pressure, blood samples, 48 hours ambulatory ECG Holter recordings, Intake of n-3 PUFAs (assessed by questionnaires and blood measurements). Perspective: A positive result of this study might make it possible to achieve a reduction in arrhythmias and mortality in these high risk patients by a cheap and well tolerated nutritional supplement.

Official Title
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Effects of Marine n-3 Fatty Acids on Heart Rate Variability and Arrhythmias in Patients Receiving Chronic Dialysis (Renal Rhythm Study II)

Conditions
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Kidney Failure Chronic, Arrhythmias Cardiac

Intervention / Treatment
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* Dietary Supplement: dietary supplement: n-3 PUFA
* Dietary Supplement: olive oil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Dialysis > 3 months Age > 18 years Signed informed consent Exclusion Criteria: Patients who is not able to consent. Known allergy to contents of the olive or fish oil capsules. Remaining life expectancy < 3 months. Pregnancy (positive S-HCG) - test only performed in cases of doubt.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: dietary supplement: n-3 PUFA<br>n-3 polyunsaturated fatty acids from fish oil capsules of 500 mg. 2 g a day. | Dietary Supplement: dietary supplement: n-3 PUFA<br> <br> * Other names: Calamarine 250/250 TG;|
| Placebo Comparator: olive oil<br>Capsules of 500 mg. 2 g a day. | Dietary Supplement: olive oil<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the 24 hours time domain index: standard deviation of NN-intervals (SDNN) in milliseconds (ms) | Evaluated using 48 hours Holter ECG recordings at baseline and after 3 months. | baseline and 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change in number of episodes with supraventricular tachycardia per day | evaluated using 48 hours Holter ECG recordings at baseline and after 3 months. | baseline and 3 months | 
| change in number of premature atrial complexes per day | evaluated using 48 hours Holter ECG recordings at baseline and after 3 months. | baseline and 3 months | 
| change in Lown class of premature ventricular complexes | Evaluated using 48 hours Holter ECG recordings at baseline and after 3 months. | baseline and 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Renal Dialysis, Arrhythmias Cardiac, Death Sudden Cardiac, Fatty Acids Omega 3