Vitamin D and Cardiac Autonomic Tone in Hemodialysis (VITAH)

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2013 by University of Calgary
Sponsor:
Collaborators:
Alberta Innovates Health Solutions
Canadian Institute of Health Research - Doctoral Research Award: Patient-oriented Research
Information provided by (Responsible Party):
Sofia Ahmed, University of Calgary
ClinicalTrials.gov Identifier:
NCT01774812
First received: January 17, 2013
Last updated: August 23, 2013
Last verified: August 2013
  Purpose

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.


Condition Intervention Phase
Cardiovascular Disease
Sudden Cardiac Death
Dietary Supplement: Alfacalcidol
Dietary Supplement: Ergocalciferol
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Vitamin D Supplementation and Cardiac Autonomic Tone in Hemodialysis Patients: A Blinded, Randomized-controlled Trial

Resource links provided by NLM:


Further study details as provided by University of Calgary:

Primary Outcome Measures:
  • LF:HF [ Time Frame: change from baseline to 6 weeks ] [ Designated as safety issue: No ]
    Low frequency to high frequency ratio (sympathetic vs. parasympathetic cardiac autonomic power)

  • LF:HF [ Time Frame: change from 6 weeks to 18 weeks ] [ Designated as safety issue: No ]
    Low frequency to high frequency ratio (sympathetic vs. parasympathetic cardiac autonomic power)

  • LF:HF [ Time Frame: change from 18 weeks to 24 weeks ] [ Designated as safety issue: No ]
    Low frequency to high frequency ratio (sympathetic vs. parasympathetic cardiac autonomic power)


Secondary Outcome Measures:
  • SDNN [ Time Frame: every 3 weeks up to 24 weeks ] [ Designated as safety issue: No ]
    standard deviation of normal wave (heart rate variability time domain)

  • SDANN [ Time Frame: every 3 weeks up to 24 weeks ] [ Designated as safety issue: No ]
    standard deviation of the average normal wave (heart rate variability time domain)

  • pNN50% [ Time Frame: every 3 weeks up to 24 weeks ] [ Designated as safety issue: No ]
    percentage of normal waves which differ in frequency > 50 ms compared to the wave directly before (heart rate variability time domain)

  • LF [ Time Frame: every 3 weeks up to 24 weeks ] [ Designated as safety issue: No ]
    Low-frequency (ms squared and normalized units), thought to reflect sympathetic contribution from the cardiac autonomic nervous system

  • HF [ Time Frame: every 3 weeks up to 24 weeks ] [ Designated as safety issue: No ]
    High-frequency (ms squared and normalized units), thought to reflect parasympathetic contribution from the cardiac autonomic nervous system


Other Outcome Measures:
  • 25-hydroxy vitamin D [ Time Frame: every 3 weeks up to 24 weeks ] [ Designated as safety issue: No ]
  • 1,25-dihydroxyvitamin D [ Time Frame: every 3 weeks up to 24 weeks ] [ Designated as safety issue: No ]
  • Parathyroid hormone [ Time Frame: every 3 weeks up to 24 weeks ] [ Designated as safety issue: No ]
  • Calcium [ Time Frame: every 3 weeks up to 24 weeks ] [ Designated as safety issue: No ]
  • Phosphate [ Time Frame: every 3 weeks up to 24 weeks ] [ Designated as safety issue: No ]
  • Pre- and post-dialysis weight [ Time Frame: every 3 weeks up to 24 weeks ] [ Designated as safety issue: No ]
  • Blood pressure [ Time Frame: every 3 weeks up to 24 weeks ] [ Designated as safety issue: No ]
    systolic, diastolic

  • Kt/V [ Time Frame: every 3 weeks up to 24 weeks ] [ Designated as safety issue: No ]
  • Epinephrine [ Time Frame: every 3 weeks up to 24 weeks ] [ Designated as safety issue: No ]
  • Norepinephrine [ Time Frame: every 3 weeks up to 24 weeks ] [ Designated as safety issue: No ]
  • Renin-angiotensin system activity (circulating) [ Time Frame: every 3 weeks up to 24 weeks ] [ Designated as safety issue: No ]
    renin, angiotensin II, aldosterone


Estimated Enrollment: 60
Study Start Date: January 2013
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 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)
Dietary Supplement: Alfacalcidol
0.25 mcg 3x per week for 6 weeks
Dietary Supplement: Ergocalciferol
50,000IU 1x per week for 6 weeks
Active Comparator: 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
Dietary Supplement: Alfacalcidol
0.25 mcg 3x per week for 6 weeks
Dietary Supplement: Ergocalciferol
50,000IU 1x per week for 6 weeks

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01774812

Contacts
Contact: Dr. Sofia B Ahmed, MD, MMSc (403) 944-2745 sofia.ahmed@albertahealthservices.ca
Contact: Michelle C Mann, PhD(c.), BSc (403) 479-2908 mcmann@ucalgary.ca

Locations
Canada, Alberta
Sheldon M. Chumir Health Centre Recruiting
Calgary, Alberta, Canada, T2R 0X7
Contact: Janice Mackay, RN, CNeph    (403) 955-6387    janice.mackay@albertahealthservices.ca   
Contact: Troy Hamilton    403-955-6385    tdhamilt@ucalgary.ca   
Principal Investigator: Dr. Sofia B Ahmed, MD, MMSc         
Foothills Medical Centre - University of Calgary Not yet recruiting
Calgary, Alberta, Canada, T2N 2T9
Contact: Darlene Sola, RN, BScN    (403) 944-2745    dsola@ucalgary.ca   
Principal Investigator: Dr. Sofia B Ahmed, MD, MMSc         
Northland Hemodialysis Clinic Not yet recruiting
Calgary, Alberta, Canada, T2L 2J8
Principal Investigator: Dr. Sofia B Ahmed, MD, MMSc         
Sponsors and Collaborators
University of Calgary
Alberta Innovates Health Solutions
Canadian Institute of Health Research - Doctoral Research Award: Patient-oriented Research
Investigators
Principal Investigator: 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
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Sofia Ahmed, Dr. Sofia B. Ahmed, University of Calgary
ClinicalTrials.gov Identifier: NCT01774812     History of Changes
Other Study ID Numbers: UC-Neph-2012001
Study First Received: January 17, 2013
Last Updated: August 23, 2013
Health Authority: Canada: Health Canada

Keywords provided by University of Calgary:
vitamin D
hemodialysis
sudden cardiac death
heart rate variability
cardiac autonomic tone

Additional relevant MeSH terms:
Death, Sudden, Cardiac
Cardiovascular Diseases
Death
Pathologic Processes
Heart Arrest
Heart Diseases
Death, Sudden
Ergocalciferols
Vitamin D
Vitamins
Hydroxycholecalciferols
Alfacalcidol
Micronutrients
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Bone Density Conservation Agents

ClinicalTrials.gov processed this record on September 14, 2014