Vitamin D and Cardiac Autonomic Tone in Hemodialysis

Cardiovascular Disease Clinical Trial

— VITAH  

Official title:

Vitamin D Supplementation and Cardiac Autonomic Tone in Hemodialysis Patients: A Blinded, Randomized-controlled Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01774812
• Other study ID #: UC-Neph-2012001
• Status: Completed
• Phase: Phase 2
• First received: January 17, 2013
• Last updated: August 29, 2016
• Start date: January 2013
• Est. completion date: March 2015

Study information

• Verified date: August 2016
• Source: University of Calgary
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health Canada
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 56
• Est. completion date: March 2015
• Est. primary completion date: March 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Cardiovascular Disease
• Cardiovascular Diseases
• Death
• Death, Sudden, Cardiac
• Sudden Cardiac Death

Intervention

Dietary Supplement:
• Alfacalcidol
0.25 mcg 3x per week for 6 weeks
• Ergocalciferol
50,000IU 1x per week for 6 weeks

Locations

Country	Name	City	State
Canada	Foothills Medical Centre - University of Calgary	Calgary	Alberta
Canada	Northland Hemodialysis Clinic	Calgary	Alberta
Canada	Sheldon M. Chumir Health Centre	Calgary	Alberta

Sponsors (3)

Lead Sponsor	Collaborator
University of Calgary	Alberta Innovates Health Solutions, Canadian Institutes of Health Research (CIHR)

Country where clinical trial is conducted

Canada, 

References & Publications (4)

Drechsler C, Pilz S, Obermayer-Pietsch B, Verduijn M, Tomaschitz A, Krane V, Espe K, Dekker F, Brandenburg V, März 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. — View 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. Review. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	25-hydroxy vitamin D		every 6 weeks up to 24 weeks	No
Other	1,25-dihydroxyvitamin D		every 6 weeks up to 24 weeks	No
Other	Parathyroid hormone		every 6 weeks up to 24 weeks	No
Other	Calcium		every 6 weeks up to 24 weeks	No
Other	Phosphate		every 6 weeks up to 24 weeks	No
Other	Pre- and post-dialysis weight		every 6 weeks up to 24 weeks	No
Other	Epinephrine		every 6 weeks up to 24 weeks	No
Other	Norepinephrine		every 6 weeks up to 24 weeks	No
Other	Renin-angiotensin system activity (circulating)	renin, angiotensin II, aldosterone	every 6 weeks up to 24 weeks	No
Primary	LF:HF	Low frequency to high frequency ratio (sympathetic vs. parasympathetic cardiac autonomic power)	change from baseline to 6 weeks	No
Primary	LF:HF	Low frequency to high frequency ratio (sympathetic vs. parasympathetic cardiac autonomic power)	change from 6 weeks to 18 weeks	No
Primary	LF:HF	Low frequency to high frequency ratio (sympathetic vs. parasympathetic cardiac autonomic power)	change from 18 weeks to 24 weeks	No
Secondary	SDNN	standard deviation of normal wave (heart rate variability time domain)	every 6 weeks up to 24 weeks	No
Secondary	SDANN	standard deviation of the average normal wave (heart rate variability time domain)	every 6 weeks up to 24 weeks	No
Secondary	pNN50%	percentage of normal waves which differ in frequency > 50 ms compared to the wave directly before (heart rate variability time domain)	every 6 weeks up to 24 weeks	No
Secondary	LF	Low-frequency (ms squared and normalized units), thought to reflect sympathetic contribution from the cardiac autonomic nervous system	every 6 weeks up to 24 weeks	No
Secondary	HF	High-frequency (ms squared and normalized units), thought to reflect parasympathetic contribution from the cardiac autonomic nervous system	every 6 weeks up to 24 weeks	No