Cardiovascular DiseasePhase 2VITAHNCT01774812
Vitamin D and Cardiac Autonomic Tone in Hemodialysis
A Phase 2 study testing Alfacalcidol and Ergocalciferol in people with Cardiovascular Disease and Sudden Cardiac Death, run by University of Calgary at 3 sites in Canada.
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cardiovascular Disease, Sudden Cardiac Death
- What is being tested?
- Alfacalcidol and Ergocalciferol
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 56 participants
- Where
- 3 sitesCanada
- Study dates
- Jan 2013to Mar 2015
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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)
Trial locations and contacts
3 sites in 1 country.
Canada3 sites
Northland Hemodialysis Clinic
Calgary, Alberta, T2L 2J8
Foothills Medical Centre - University of Calgary
Calgary, Alberta, T2N 2T9
Sheldon M. Chumir Health Centre
Calgary, Alberta, T2R 0X7
About this study
Official title: Vitamin D Supplementation and Cardiac Autonomic Tone in Hemodialysis Patients: A Blinded, Randomized-controlled Trial
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
- Being tested
- Alfacalcidol, Ergocalciferol
- Keywords
- vitamin D, hemodialysis, sudden cardiac death, heart rate variability, cardiac autonomic tone
- Medical subject headings
- Cardiovascular Diseases, Death, Sudden, Cardiac
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AlfacalcidolDietary supplement
0.25 mcg 3x per week for 6 weeks
ErgocalciferolDietary supplement
50,000IU 1x per week for 6 weeks
| Study group | Role | What they receive |
|---|---|---|
| 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) Receives: 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 Receives: Dietary Supplement: Alfacalcidol; Dietary Supplement: Ergocalciferol |
What is being measured
The primary outcome is the main question the study is designed to answer.
LF:HF
Low frequency to high frequency ratio (sympathetic vs. parasympathetic cardiac autonomic power)
Measured: change from baseline to 6 weeks
LF:HF
Low frequency to high frequency ratio (sympathetic vs. parasympathetic cardiac autonomic power)
Measured: change from 6 weeks to 18 weeks
LF:HF
Low frequency to high frequency ratio (sympathetic vs. parasympathetic cardiac autonomic power)
Measured: change from 18 weeks to 24 weeks
Secondary outcomes (5)
SDNN
standard deviation of normal wave (heart rate variability time domain)
Measured: every 6 weeks up to 24 weeks
SDANN
standard deviation of the average normal wave (heart rate variability time domain)
Measured: every 6 weeks up to 24 weeks
pNN50%
percentage of normal waves which differ in frequency > 50 ms compared to the wave directly before (heart rate variability time domain)
Measured: every 6 weeks up to 24 weeks
LF
Low-frequency (ms squared and normalized units), thought to reflect sympathetic contribution from the cardiac autonomic nervous system
Measured: every 6 weeks up to 24 weeks
HF
High-frequency (ms squared and normalized units), thought to reflect parasympathetic contribution from the cardiac autonomic nervous system
Measured: every 6 weeks up to 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jan 2013 (estimated)
- Study startJan 2013
- Primary completionMar 2015
- Study completionMar 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Cardiovascular DiseaseStudies of the same condition, open and under way.
- More trials run by University of CalgaryThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 56 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Calgary
- Sponsor type
- University, hospital or other
- Collaborators
- Alberta Innovates Health Solutions, Canadian Institutes of Health Research (CIHR)
- Responsible party
- Principal investigator, Sofia Ahmed, University of Calgary
- Investigators
- Dr. Sofia B Ahmed, MD, MMSc, Principal investigator, University of CalgaryDr. Derek Exner, MD, MPH, Principal investigator, University of Calgary, Libin Cardiovascular InstituteDr. Brenda Hemmelgarn, MD, PhD, MN, Principal investigator, University of Calgary
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01774812
- Sponsor's protocol ID
- UC-Neph-2012001
- Acronym
- VITAH
- Status last verified
- Aug 2016
- First submitted
- 17 Jan 2013
- Last updated
- 31 Aug 2016
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 22223455Drechsler 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.
PubMed 20688781Lahiri 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.
PubMed 18452777Mann 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.
PubMed 23752493Mann 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.
PubMed 27690095Mann 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.
PubMed 25098377
Study at a glance
From the registry record, last updated by the sponsor on 31 Aug 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Vitamin D Supplementation and Cardiac Autonomic Tone in Hemodialysis Patients: A Blinded, Randomized-controlled Trial
- ClinicalTrials.gov ID
- NCT01774812
- Acronym / sponsor ID
- VITAH / UC-Neph-2012001
- Conditions
- Cardiovascular Disease, Sudden Cardiac Death
- Keywords
- vitamin D, hemodialysis, sudden cardiac death, heart rate variability, cardiac autonomic tone
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 56 participants (actual)
- Lead sponsor
- University of CalgaryUniversity, hospital or other
- Collaborators
- Alberta Innovates Health Solutions, Canadian Institutes of Health Research (CIHR)
- Study start
- Jan 2013
- Primary completion
- Mar 2015 (actual)
- Study completion
- Mar 2015 (actual)
- First posted
- 24 Jan 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Vitamin D Sequence 1 | Active comparator | Dietary Supplement: Alfacalcidol, Dietary Supplement: Ergocalciferol6 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) |
| Vitamin D Treatment Sequence 2 | Active comparator | Dietary Supplement: Alfacalcidol, Dietary Supplement: Ergocalciferol6 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (3 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Alfacalcidol0.25 mcg 3x per week for 6 weeks | Dietary supplement | Vitamin D Sequence 1, Vitamin D Treatment Sequence 2 |
| Ergocalciferol50,000IU 1x per week for 6 weeks | Dietary supplement | Vitamin D Sequence 1, Vitamin D Treatment Sequence 2 |
Primary outcome
LF:HF
Time frame: change from baseline to 6 weeks
Low frequency to high frequency ratio (sympathetic vs. parasympathetic cardiac autonomic power)
LF:HF
Time frame: change from 6 weeks to 18 weeks
Low frequency to high frequency ratio (sympathetic vs. parasympathetic cardiac autonomic power)
LF:HF
Time frame: change from 18 weeks to 24 weeks
Low frequency to high frequency ratio (sympathetic vs. parasympathetic cardiac autonomic power)
5 secondary outcomes
SDNN
Time frame: every 6 weeks up to 24 weeks
SDANN
Time frame: every 6 weeks up to 24 weeks
pNN50%
Time frame: every 6 weeks up to 24 weeks
LF
Time frame: every 6 weeks up to 24 weeks
HF
Time frame: every 6 weeks up to 24 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Aug 2016.
- Background: PubMed 22223455Mann 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.
- Background: PubMed 20688781Drechsler 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.
- Background: PubMed 18452777Lahiri 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.
- Background: PubMed 23752493Mann 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.
- Derived from this study: PubMed 27690095Mann 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.
- Derived from this study: PubMed 25098377Mann 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dr. Sofia B Ahmed, MD, MMSc principal investigator
University of Calgary
Dr. Derek Exner, MD, MPH principal investigator
University of Calgary, Libin Cardiovascular Institute
Dr. Brenda Hemmelgarn, MD, PhD, MN principal investigator
University of Calgary
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Alfacalcidol and Ergocalciferol in people with Cardiovascular Disease and Sudden Cardiac Death, run by University of Calgary at 3 sites in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 31 Aug 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
LF:HF (time frame: change from baseline to 6 weeks). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01774812, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Aug 2016.