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| Name | Class |
|---|---|
| Alberta Innovates Health Solutions | OTHER |
| Canadian Institutes of Health Research (CIHR) | OTHER_GOV |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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) |
|
| 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 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Alfacalcidol | Dietary Supplement | 0.25 mcg 3x per week for 6 weeks |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| SDNN | standard deviation of normal wave (heart rate variability time domain) | every 6 weeks up to 24 weeks |
| SDANN | standard deviation of the average normal wave (heart rate variability time domain) |
| Measure | Description | Time Frame |
|---|---|---|
| 25-hydroxy vitamin D | every 6 weeks up to 24 weeks | |
| 1,25-dihydroxyvitamin D | every 6 weeks up to 24 weeks | |
| Parathyroid hormone |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| 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 |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Northland Hemodialysis Clinic | Calgary | Alberta | T2L 2J8 | Canada | ||
| Foothills Medical Centre - University of Calgary |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 22223455 | Background | 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. | |
| 20688781 | 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. |
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| ID | Term |
|---|---|
| D002318 | Cardiovascular Diseases |
| D016757 | Death, Sudden, Cardiac |
| ID | Term |
|---|---|
| D006323 | Heart Arrest |
| D006331 | Heart Diseases |
| D003645 | Death, Sudden |
| D003643 | Death |
| D010335 |
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| ID | Term |
|---|---|
| C008088 | alfacalcidol |
| D004872 | Ergocalciferols |
| ID | Term |
|---|---|
| D002782 | Cholestenes |
| D002776 | Cholestanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
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| Ergocalciferol | Dietary Supplement | 50,000IU 1x per week for 6 weeks |
|
| 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) | 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 | 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 | every 6 weeks up to 24 weeks |
| every 6 weeks up to 24 weeks |
| Calcium | every 6 weeks up to 24 weeks |
| Phosphate | every 6 weeks up to 24 weeks |
| Pre- and post-dialysis weight | every 6 weeks up to 24 weeks |
| Epinephrine | every 6 weeks up to 24 weeks |
| Norepinephrine | every 6 weeks up to 24 weeks |
| Renin-angiotensin system activity (circulating) | renin, angiotensin II, aldosterone | every 6 weeks up to 24 weeks |
| Calgary |
| Alberta |
| T2N 2T9 |
| Canada |
| Sheldon M. Chumir Health Centre | Calgary | Alberta | T2R 0X7 | Canada |
| 18452777 | 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. |
| 23752493 | 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. |
| 27690095 | Derived | 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. |
| 25098377 | 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. |
| Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D011083 |
| Polycyclic Compounds |
| D013261 | Sterols |
| D014807 | Vitamin D |
| D012632 | Secosteroids |
| D008563 | Membrane Lipids |
| D008055 | Lipids |