The VITAH Trial Vitamin D supplementation and cardiac autonomic tone in hemodialysis: a blinded, randomized controlled trial

Abstract

BACKGROUND: Patients with end-stage kidney disease (ESKD) have a high rate of mortality and specifically an increased risk of sudden cardiac death (SCD). Impaired cardiac autonomic tone is associated with elevated risk of SCD. Moreover, patients with ESKD are often vitamin D deficient, which we have shown may be linked to autonomic dysfunction in humans. To date, it is not known whether vitamin D supplementation normalizes cardiac autonomic function in the high-risk ESKD population. The VITamin D supplementation and cardiac Autonomic tone in Hemodialysis (VITAH) randomized trial will determine whether intensive vitamin D supplementation therapies improve cardiac autonomic tone to a greater extent than conventional vitamin D supplementation regimens in ESKD patients requiring chronic hemodialysis. METHODS/DESIGN: A total of 60 subjects with ESKD requiring thrice weekly chronic hemodialysis will be enrolled in this 2x2 crossover, blinded, randomized controlled trial. Following a 4-week washout period from any prior vitamin D therapy, subjects are randomized 1:1 to intensive versus standard vitamin D therapy for 6 weeks, followed by a 12-week washout period, and finally the remaining treatment arm for 6 weeks. Intensive vitamin D treatment includes alfacalcidiol (activated vitamin D) 0.25mcg orally with each dialysis session combined with ergocalciferol (nutritional vitamin D) 50 000 IU orally once per week and placebo the remaining two dialysis days for 6 weeks. The standard vitamin D treatment includes alfacalcidiol 0.25mcg orally combined with placebo each dialysis session per week for 6 weeks. Cardiac autonomic tone is measured via 24 h Holter monitor assessments on the first dialysis day of the week every 6 weeks throughout the study period. The primary outcome is change in the low frequency: high frequency heart rate variability (HRV) ratio during the first 12 h of the Holter recording at 6 weeks versus baseline. Secondary outcomes include additional measures of HRV. The safety of intensive versus conventional vitamin D supplementation is also assessed. DISCUSSION: VITAH will determine whether an intensive vitamin D supplementation regimen will improve cardiac autonomic tone compared to conventional vitamin D supplementation and will assess the safety of these two supplementation regimens in ESKD patients receiving chronic hemodialysis. TRIAL REGISTRATION: ClinicalTrials.gov, NCT0177481