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Unable to recruit sufficient number of patients.
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The central objective of this proposal is to establish that vitamin D supplementation in heart failure patients with low vitamin D levels will have improved outcomes compared to placebo. In addition the investigators will also evaluate the role of genetics in regard to vitamin D and heart failure. The investigators will be evaluating what is currently a novel approach of identifying patients with low vitamin D and treating this low vitamin D level. The investigators will be able to evaluate the importance of vitamin D supplementation in these patients and the role of genetics on our defined outcomes.
Primary Objective To determine how rapid vitamin D supplementation affects biomarkers and submaximal exercise capacity in systolic HF patients with low vitamin D status.
Working Hypothesis 1: HF patients when supplemented with vitamin D for 6 months will have lower measures of inflammation and extracellular-matrix remodeling compared with placebo.
Working Hypothesis 2: HF patients when supplemented with vitamin D for 6 months will have longer 6-minute walk length compared with placebo.
Secondary Objectives To establish a relationship between the CYP2R1 variant and surrogate markers in systolic HF patients.
Working Hypothesis 3: HF patients with the CYP2R1 G allele will have higher measures of inflammation and extracellular-matrix remodeling compared to AA subjects. This relationship will also be seen in subjects with the CYP2R1 TagSNP variants.
Working Hypothesis 4: HF patients with CYP2R1 variant alleles will have shorter 6-minute walk length compared to subjects without these variants.
To genotype HF subjects for the VDR variants and additional tag SNPs, to ascertain the relationship between VDR genetic variation and surrogate markers in systolic HF patients.
Working Hypothesis 5: HF patients with VDR variants will have greater measures of inflammation and extracellular-matrix remodeling compared to subjects without VDR variants.
Working Hypothesis 6: HF patients with VDR variants will have a shorter 6-minute walk length compared to subjects without these variants.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Vitamin D | Active Comparator | Vitamin D supplementation will be an oral load of 100,000 IU then 2000 IU by mouth daily of vitamin D3 (cholecalciferol)for 6 months |
|
| Placebo | Placebo Comparator | A placebo loading dose will be given followed by two placebo tablets daily for 6 months. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Vitamin D3 | Drug | Vitamin D supplementation will be an oral load of 100,000 IU then 2000 IU by mouth daily of vitamin D3 (cholecalciferol)for 6 months |
|
| Measure | Description | Time Frame |
|---|---|---|
| Biomarkers | Biomarkers - C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-a (TNF-a), propeptide procollagen type I, plasma procollagen III, matrix metalloproteinase 2 (MMP-2), MMP-9 and tissue inhibitor of matrix metalloproteinases-1 (TIMP-1). | 6 months |
| Measure | Description | Time Frame |
|---|---|---|
| Exercise Capacity Measured by 6 Minute Walk Test | 6 months | |
| Quality of Life Measured by Kansas City Cardiomyopathy Questionnaire | Kansas City Cardiomyopathy Questionnaire for quality of life is measured on a scale of 0 - 100, with 100 being best. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Barry E. Bleske, Pharm. D. | University of Michigan | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Michigan Medical Center | Ann Arbor | Michigan | 48109 | United States |
16 consented participants were not randomized due to screen fails.
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| ID | Title | Description |
|---|---|---|
| FG000 | Vitamin D | Vitamin D supplementation will be an oral load of 100,000 IU then 2000 IU by mouth daily of vitamin D3 (cholecalciferol)for 6 months Vitamin D3: Vitamin D supplementation will be an oral load of 100,000 IU then 2000 IU by mouth daily of vitamin D3 (cholecalciferol)for 6 months |
| FG001 | Placebo | A placebo loading dose will be given followed by two placebo tablets daily for 6 months. Placebo: A placebo loading dose will be given followed by 2 placebo tablets daily for 6 months. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Vitamin D | Vitamin D supplementation will be an oral load of 100,000 IU then 2000 IU by mouth daily of vitamin D3 (cholecalciferol)for 6 months Vitamin D3: Vitamin D supplementation will be an oral load of 100,000 IU then 2000 IU by mouth daily of vitamin D3 (cholecalciferol)for 6 months |
| BG001 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | Number |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Biomarkers | Biomarkers - C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-a (TNF-a), propeptide procollagen type I, plasma procollagen III, matrix metalloproteinase 2 (MMP-2), MMP-9 and tissue inhibitor of matrix metalloproteinases-1 (TIMP-1). | Because enrollment was less than 30% of original goal (6 vs 4 subjects) and therefore would not have scientific validity and would be a waste of financial resources, this outcome was not analyzed. | Posted | 6 months |
|
6 months
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Vitamin D | Vitamin D supplementation will be an oral load of 100,000 IU then 2000 IU by mouth daily of vitamin D3 (cholecalciferol)for 6 months Vitamin D3: Vitamin D supplementation will be an oral load of 100,000 IU then 2000 IU by mouth daily of vitamin D3 (cholecalciferol)for 6 months |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| GI bleed | Gastrointestinal disorders | Non-systematic Assessment |
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Only a fraction of the original goal of enrollment was met. Therefore, analysis of comparative results was not done. No conclusions of any kind can be made from analyzing the data with the number of patients completing the trial (6 vs 4 patients).
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Barry Bleske | University of Michigan | 734-763-3232 | bbleske@umich.edu |
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| ID | Term |
|---|---|
| D006333 | Heart Failure |
| D009043 | Motor Activity |
| ID | Term |
|---|---|
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
| D001519 | Behavior |
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| ID | Term |
|---|---|
| D002762 | Cholecalciferol |
| D000073893 | Sugars |
| ID | Term |
|---|---|
| D002782 | Cholestenes |
| D002776 | Cholestanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
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| Placebo | Drug | A placebo loading dose will be given followed by 2 placebo tablets daily for 6 months. |
|
|
| 6 months |
| Vitamin D Genomics | Genotyped for the restricted fragment length polymorphism at the BsmI site. In addition CYP2R1, CYP27B1, CYP24 will also be genotyped. | Baseline |
| Placebo |
A placebo loading dose will be given followed by two placebo tablets daily for 6 months. Placebo: A placebo loading dose will be given followed by 2 placebo tablets daily for 6 months. |
| BG002 | Total | Total of all reporting groups |
| participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Baseline Vit D level (ng/mL) | Baseline Vit D level nanograms per milliliter of blood. | Mean | Standard Deviation | ng/mL |
|
| Placebo |
A placebo loading dose will be given followed by two placebo tablets daily for 6 months. Placebo: A placebo loading dose will be given followed by 2 placebo tablets daily for 6 months. |
|
| Secondary | Exercise Capacity Measured by 6 Minute Walk Test | Because enrollment was less than 30% of original goal (6 vs 4 patients) and therefore would not have scientific validity and no conclusions could be determined, this outcome was not analyzed. | Posted | 6 months |
|
|
| Secondary | Quality of Life Measured by Kansas City Cardiomyopathy Questionnaire | Kansas City Cardiomyopathy Questionnaire for quality of life is measured on a scale of 0 - 100, with 100 being best. | Because enrollment was less than 30% of original goal (6 vs 4 patients) and therefore would not have scientific validity and no conclusions could be determined, this outcome was not analyzed. | Posted | 6 months |
|
|
| Secondary | Vitamin D Genomics | Genotyped for the restricted fragment length polymorphism at the BsmI site. In addition CYP2R1, CYP27B1, CYP24 will also be genotyped. | Because enrollment was less than 30% of original goal (6 vs 4 patients) and therefore would not have scientific validity, in addition there is significant time and costs associated with this measurement which would result in data that would lead to no conclusions, this outcome was not analyzed. | Posted | Baseline |
|
|
| 2 |
| 6 |
| 0 |
| 6 |
| EG001 | Placebo | A placebo loading dose will be given followed by two placebo tablets daily for 6 months. Placebo: A placebo loading dose will be given followed by 2 placebo tablets daily for 6 months. | 0 | 6 | 0 | 6 |
| syncope due to hypokalemia | Nervous system disorders | Non-systematic Assessment |
|
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| D011083 |
| Polycyclic Compounds |
| D013261 | Sterols |
| D014807 | Vitamin D |
| D012632 | Secosteroids |
| D008563 | Membrane Lipids |
| D008055 | Lipids |
| D002241 | Carbohydrates |