MedPath

Vitamin D and Cardiac Autonomic Tone in Hemodialysis

Phase 2
Completed
Conditions
Sudden Cardiac Death
Cardiovascular Disease
Interventions
Dietary Supplement: Alfacalcidol
Dietary Supplement: Ergocalciferol
Registration Number
NCT01774812
Lead Sponsor
University of Calgary
Brief Summary

Despite advances in treatment of conventional cardiovascular risk factors, patients with kidney disease remain at high risk for fatal cardiac events. To date, kidney disease affects approximately 2 million Canadians; however, this patient population remains grossly understudied due to the complex nature of the disease. The inadequacy of the literature to address the cardiovascular-related mortality rates in those with kidney disease reflects the urgent need for investigation of novel risk factors.

One cardiovascular risk factor which has recently been validated is the clinical measurement of cardiac autonomic tone (CAT). CAT refers to the amount of activity contributed by the stimulatory and inhibitory limbs of the cardiac autonomic nervous system, which work in concert with one another to control heart rate. CAT can be quantified computer analysis of heart rate over time, captured by a simple Holter electrocardiogram (ECG) recording. Abnormal CAT, which occurs when the autonomic system does not control heart rate properly in response to physical demands or stress, is associated with risk of adverse cardiovascular events in both healthy and high risk populations. It has recently been shown that patients with severe kidney disease demonstrate significant CAT abnormalities, thus exaggerated susceptibility to cardiac death.

Vitamin D (VD) deficiency is also common in this patient population due to the fact that the kidney plays a crucial role in VD metabolism. Given that VD deficiency is an established cardiovascular risk factor on its own, it is possible that kidney disease patients experienced compounded risk due to the combination of VD deficiency and abnormal CAT. However, no study has ever investigated whether VD deficiency influences CAT in healthy or diseased populations. To our knowledge, this will be the first trial to ever examine the effect, if any, of different VD supplementation treatments (standard of care vs. combination) on CAT in a population burdened with overwhelming risk and incidence of cardiovascular and sudden cardiac death risk.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
56
Inclusion Criteria
  • age ≥ 18 years
  • 3x weekly hemodialysis outpatient within Calgary for at least 3 months prior to enrolment
  • physician consent to participate in VD supplementation regimen
  • ability and agreement to cease any VD medication for 4 weeks prior to initiation of study
  • able to comprehend study and provide oral and written consent in English
Exclusion Criteria
  • any major cardiovascular event (new onset arrhythmia, hospitalization for a cardiac event) noted in patient chart within the 6 month period prior to initiation of the study
  • currently on VD therapy/refusal to cease VD therapy for 4 weeks prior to initiation of study
  • physician anticipates death or adverse event within the next year- known discharge from hemodialysis (transfer to peritoneal dialysis, kidney transplant)

Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
Vitamin D Sequence 1Alfacalcidol6 weeks - alfacalcidol 0.25mcg + placebo 3x per week, 12 week washout, 6 weeks - alfacalcidol 0.25mcg 3x per week + 50,000IU ergocalciferol 1x per week (placebo the 2 remaining days)
Vitamin D Sequence 1Ergocalciferol6 weeks - alfacalcidol 0.25mcg + placebo 3x per week, 12 week washout, 6 weeks - alfacalcidol 0.25mcg 3x per week + 50,000IU ergocalciferol 1x per week (placebo the 2 remaining days)
Vitamin D Treatment Sequence 2Alfacalcidol6 weeks - alfacalcidol 0.25mcg 3x per week + 50,000IU ergocalciferol 1x per week (placebo the 2 remaining days), 12 week washout, 6 weeks - alfacalcidol 0.25mcg + placebo 3x per week
Vitamin D Treatment Sequence 2Ergocalciferol6 weeks - alfacalcidol 0.25mcg 3x per week + 50,000IU ergocalciferol 1x per week (placebo the 2 remaining days), 12 week washout, 6 weeks - alfacalcidol 0.25mcg + placebo 3x per week
Primary Outcome Measures
NameTimeMethod
LF:HFchange from 18 weeks to 24 weeks

Low frequency to high frequency ratio (sympathetic vs. parasympathetic cardiac autonomic power)

Secondary Outcome Measures
NameTimeMethod
pNN50%every 6 weeks up to 24 weeks

percentage of normal waves which differ in frequency \> 50 ms compared to the wave directly before (heart rate variability time domain)

LFevery 6 weeks up to 24 weeks

Low-frequency (ms squared and normalized units), thought to reflect sympathetic contribution from the cardiac autonomic nervous system

SDNNevery 6 weeks up to 24 weeks

standard deviation of normal wave (heart rate variability time domain)

HFevery 6 weeks up to 24 weeks

High-frequency (ms squared and normalized units), thought to reflect parasympathetic contribution from the cardiac autonomic nervous system

SDANNevery 6 weeks up to 24 weeks

standard deviation of the average normal wave (heart rate variability time domain)

Trial Locations

Locations (3)

Sheldon M. Chumir Health Centre

🇨🇦

Calgary, Alberta, Canada

Foothills Medical Centre - University of Calgary

🇨🇦

Calgary, Alberta, Canada

Northland Hemodialysis Clinic

🇨🇦

Calgary, Alberta, Canada

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