Vitamin D and Cardiac Autonomic Tone in Hemodialysis

NCT01774812 | Completed Phase 2 DMC

• 1 other identifier: UC-Neph-2012001
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 3

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.

Conditions

Cardiovascular Disease; Sudden Cardiac Death

Keywords

vitamin D; hemodialysis; sudden cardiac death; heart rate variability; cardiac autonomic tone

Outcome Measures

Primary Outcomes (3)

• LF:HF

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

  change from baseline to 6 weeks

• LF:HF

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

  change from 6 weeks to 18 weeks

• LF:HF

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

  change from 18 weeks to 24 weeks

Secondary Outcomes (5)

• SDNN

  every 6 weeks up to 24 weeks

• SDANN

  every 6 weeks up to 24 weeks

• pNN50%

  every 6 weeks up to 24 weeks

• LF

  every 6 weeks up to 24 weeks

• HF

  every 6 weeks up to 24 weeks

Other Outcomes (9)

• 25-hydroxy vitamin D

  every 6 weeks up to 24 weeks

• 1,25-dihydroxyvitamin D

  every 6 weeks up to 24 weeks

• Parathyroid hormone

  every 6 weeks up to 24 weeks

Study Arms (2)

Vitamin D Sequence 1

ACTIVE COMPARATOR

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)

Dietary Supplement: Alfacalcidol; Dietary Supplement: Ergocalciferol

Vitamin D Treatment Sequence 2

ACTIVE COMPARATOR

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

Dietary Supplement: Alfacalcidol; Dietary Supplement: Ergocalciferol

Interventions

Alfacalcidol DIETARY_SUPPLEMENT

0.25 mcg 3x per week for 6 weeks

Vitamin D Sequence 1; Vitamin D Treatment Sequence 2

Ergocalciferol DIETARY_SUPPLEMENT

50,000IU 1x per week for 6 weeks

Vitamin D Sequence 1; Vitamin D Treatment Sequence 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• age ≥ 18 years
• x 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• University of Calgary: lead
• Alberta Innovates Health Solutions: collaborator
• Canadian Institutes of Health Research (CIHR): collaborator

Study Sites (3)

Northland Hemodialysis Clinic

Calgary, Alberta, T2L 2J8, Canada

Location

Foothills Medical Centre - University of Calgary

Calgary, Alberta, T2N 2T9, Canada

Location

Sheldon M. Chumir Health Centre

Calgary, Alberta, T2R 0X7, Canada

Location

Related Publications (6)

• 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.

  PMID: 22223455 BACKGROUND

• 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.

  PMID: 20688781 BACKGROUND

• 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.

  PMID: 18452777 BACKGROUND

• 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.

  PMID: 23752493 BACKGROUND

• 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.

  PMID: 27690095 DERIVED

• 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.

  PMID: 25098377 DERIVED

MeSH Terms

Conditions

Cardiovascular Diseases; Death, Sudden, Cardiac

Interventions

alfacalcidol; Ergocalciferols

Condition Hierarchy (Ancestors)

Heart Arrest; Heart Diseases; Death, Sudden; Death; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cholestenes; Cholestanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Sterols; Vitamin D; Secosteroids; Membrane Lipids; Lipids

Study Officials

• Dr. Sofia B Ahmed, MD, MMSc

  University of Calgary

  PRINCIPAL INVESTIGATOR

• Dr. Derek Exner, MD, MPH

  University of Calgary, Libin Cardiovascular Institute

  PRINCIPAL INVESTIGATOR

• Dr. Brenda Hemmelgarn, MD, PhD, MN

  University of Calgary

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr. Sofia B. Ahmed

Study Record Dates

• First Submitted: January 17, 2013
• First Posted: January 24, 2013
• Study Start: January 1, 2013
• Primary Completion: March 1, 2015
• Study Completion: March 1, 2015
• Last Updated: August 31, 2016

Record last verified: 2016-08

Locations

CA (3)