Clinical trial NCT01774812: Vitamin D and Cardiac Autonomic Tone in Hemodialysis
Official title: Vitamin D Supplementation and Cardiac Autonomic Tone in Hemodialysis Patients: A Blinded, Randomized-controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cardiovascular Disease
Sudden Cardiac Death
Keywords: vitamin D
hemodialysis
sudden cardiac death
heart rate variability
cardiac autonomic tone
Lead sponsor: University of Calgary
Sponsor class: OTHER
Collaborators: name: Alberta Innovates Health Solutions
name: Canadian Institutes of Health Research (CIHR)
First posted: 2013-01-24
Enrollment: 56
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: PREVENTION

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.


Eligibility criteria: 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)

Primary outcomes:
measure: LF:HF
timeFrame: change from baseline to 6 weeks
measure: LF:HF
timeFrame: change from 6 weeks to 18 weeks
measure: LF:HF
timeFrame: change from 18 weeks to 24 weeks
Secondary outcomes:
measure: SDNN
timeFrame: every 6 weeks up to 24 weeks
measure: SDANN
timeFrame: every 6 weeks up to 24 weeks
measure: pNN50%
timeFrame: every 6 weeks up to 24 weeks
measure: LF
timeFrame: every 6 weeks up to 24 weeks
measure: HF
timeFrame: every 6 weeks up to 24 weeks
Other outcomes:
measure: 25-hydroxy vitamin D
timeFrame: every 6 weeks up to 24 weeks
measure: 1,25-dihydroxyvitamin D
timeFrame: every 6 weeks up to 24 weeks
measure: Parathyroid hormone
timeFrame: every 6 weeks up to 24 weeks
measure: Calcium
timeFrame: every 6 weeks up to 24 weeks
measure: Phosphate
timeFrame: every 6 weeks up to 24 weeks
measure: Pre- and post-dialysis weight
timeFrame: every 6 weeks up to 24 weeks
measure: Epinephrine
timeFrame: every 6 weeks up to 24 weeks
measure: Norepinephrine
timeFrame: every 6 weeks up to 24 weeks
measure: Renin-angiotensin system activity (circulating)
timeFrame: every 6 weeks up to 24 weeks
Locations:
city: Calgary
country: Canada
facility: Northland Hemodialysis Clinic
state: Alberta
city: Calgary
country: Canada
facility: Foothills Medical Centre - University of Calgary
state: Alberta
city: Calgary
country: Canada
facility: Sheldon M. Chumir Health Centre
state: Alberta
Study officials:
affiliation: University of Calgary
name: Dr. Sofia B Ahmed, MD, MMSc
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Calgary, Libin Cardiovascular Institute
name: Dr. Derek Exner, MD, MPH
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Calgary
name: Dr. Brenda Hemmelgarn, MD, PhD, MN
role: PRINCIPAL_INVESTIGATOR
References:
citation: Mann MC, Exner DV, Hemmelgarn BR, Turin TC, Sola DY, Ahmed SB. Impact of gender on the cardiac autonomic response to angiotensin II in healthy humans. J Appl Physiol (1985). 2012 Mar;112(6):1001-7. doi: 10.1152/japplphysiol.01207.2011. Epub 2012 Jan 5.
citation: Drechsler C, Pilz S, Obermayer-Pietsch B, Verduijn M, Tomaschitz A, Krane V, Espe K, Dekker F, Brandenburg V, Marz W, Ritz E, Wanner C. Vitamin D deficiency is associated with sudden cardiac death, combined cardiovascular events, and mortality in haemodialysis patients. Eur Heart J. 2010 Sep;31(18):2253-61. doi: 10.1093/eurheartj/ehq246. Epub 2010 Aug 5.
citation: Lahiri MK, Kannankeril PJ, Goldberger JJ. Assessment of autonomic function in cardiovascular disease: physiological basis and prognostic implications. J Am Coll Cardiol. 2008 May 6;51(18):1725-33. doi: 10.1016/j.jacc.2008.01.038.
citation: Mann MC, Exner DV, Hemmelgarn BR, Sola DY, Turin TC, Ellis L, Ahmed SB. Vitamin D levels are associated with cardiac autonomic activity in healthy humans. Nutrients. 2013 Jun 10;5(6):2114-27. doi: 10.3390/nu5062114.
citation: Mann MC, Exner DV, Hemmelgarn BR, Hanley DA, Turin TC, MacRae JM, Wheeler DC, Sola DY, Ramesh S, Ahmed SB. The VITAH Trial-Vitamin D Supplementation and Cardiac Autonomic Tone in Patients with End-Stage Kidney Disease on Hemodialysis: A Blinded, Randomized Controlled Trial. Nutrients. 2016 Sep 28;8(10):608. doi: 10.3390/nu8100608.
citation: Mann MC, Exner DV, Hemmelgarn BR, Hanley DA, Turin TC, MacRae JM, Ahmed SB. The VITAH trial VITamin D supplementation and cardiac Autonomic tone in Hemodialysis: a blinded, randomized controlled trial. BMC Nephrol. 2014 Aug 6;15:129. doi: 10.1186/1471-2369-15-129.