Vitamin D Supplementation and Cardiac Autonomic Tone in Hemodialysis Patients: A Blinded, Randomized-controlled Trial
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- University of Calgary
- Enrollment
- 56
- Locations
- 3
- Primary Endpoint
- LF:HF
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Prevention
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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)
Arms & Interventions
Vitamin D Treatment Sequence 2
6 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
Intervention: Ergocalciferol (Dietary Supplement)
Vitamin D Treatment Sequence 2
6 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
Intervention: Alfacalcidol (Dietary Supplement)
Vitamin D Sequence 1
6 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)
Intervention: Ergocalciferol (Dietary Supplement)
Vitamin D Sequence 1
6 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)
Intervention: Alfacalcidol (Dietary Supplement)
Outcomes
Primary Outcomes
LF:HF
Time Frame: change from 18 weeks to 24 weeks
Low frequency to high frequency ratio (sympathetic vs. parasympathetic cardiac autonomic power)
LF:HF
Time Frame: change from baseline to 6 weeks
Low frequency to high frequency ratio (sympathetic vs. parasympathetic cardiac autonomic power)
LF:HF
Time Frame: change from 6 weeks to 18 weeks
Low frequency to high frequency ratio (sympathetic vs. parasympathetic cardiac autonomic power)
Secondary Outcomes
- pNN50%(every 6 weeks up to 24 weeks)
- LF(every 6 weeks up to 24 weeks)
- SDNN(every 6 weeks up to 24 weeks)
- HF(every 6 weeks up to 24 weeks)
- SDANN(every 6 weeks up to 24 weeks)
Investigators
Sofia Ahmed
Dr. Sofia B. Ahmed
University of Calgary