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

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

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.

Study Overview

• Status: Completed
• Conditions: Kidney Failure Chronic; Arrhythmias Cardiac
• Intervention / Treatment: Dietary supplement: olive oil; Dietary supplement: dietary supplement: n-3 PUFA

• Study Type: Interventional
• Enrollment (Actual): 112
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Aalborg, Denmark, 9000
    • Aalborg University Hospital, Department of Nephrology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
change in frequency domain indices of heart rate variability	total power (TP), Ultra low frequency (ULF), Very low frequency (VLF), low frequency (LF), high frequency (HF) and LF/HF. Evaluated using 48 hour Holter ECG recordings at baseline and after 3 months	baseline and 3 months
change in other 24 hour time domain indices of heart rate variability	mean NN (ms), sNN50 (counts), sNN6%(counts), SDNNi (ms), SDANN (ms), RMSSD (ms), triangle index. Evaluated using 48 hours Holter ECG recordings at baseline and after 3 months.	baseline and 3 months

Collaborators and Investigators

• Sponsor: Aalborg University Hospital
• Investigators: Principal Investigator: Jesper M Rantanen, MD, Department of Nephrology Aalborg University Hospital; Study Director: Jeppe H Christensen, DMSc, Department of Nephrology Aalborg University Hospital

Study record dates

Study Major Dates

• Study Start: June 1, 2014
• Primary Completion (Actual): February 1, 2016
• Study Completion (Actual): March 1, 2016

Study Registration Dates

• First Submitted: May 21, 2014
• First Submitted That Met QC Criteria: May 23, 2014
• First Posted (Estimate): May 28, 2014

Study Record Updates

• Last Update Posted (Estimate): July 27, 2016
• Last Update Submitted That Met QC Criteria: July 26, 2016
• Last Verified: July 1, 2016

More Information

Terms related to this study

• Keywords: Renal Dialysis; Arrhythmias Cardiac; Death Sudden Cardiac; Fatty Acids Omega 3
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Kidney Diseases; Urologic Diseases; Renal Insufficiency, Chronic; Kidney Failure, Chronic; Renal Insufficiency; Arrhythmias, Cardiac
• Other Study ID Numbers: N-20140013