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Patients requiring hemodialysis following kidney failure need a form of dialysis vascular access in order to undergo the dialysis procedure. Dialysis vascular access dysfunction is an enormous clinical problem. While the best form of vascular access is the arteriovenous fistula (AVF), its primary problem is early, aggressive cellular ingrowth that leads to poor maturation of the vessel, preventing its use for dialysis. Strategies to prevent AVF failure are needed.
Vitamin D is a hormone present in all human bodies and is important for good bone formation and immune function. There is new information that links vitamin D to the function of our veins and arteries, which are used in the creation of an arteriovenous fistulae. Our bodies can make vitamin D and can also get vitamin D from our diet. However, a majority of patients with chronic kidney disease and end-stage renal disease (ESRD) have low vitamin D levels (vitamin D deficiency). There are several benefits to correcting low vitamin D levels, however, it is not know whether correcting low vitamin D in the body will lead to better function of the vein and artery used for arteriovenous fistulae creation. The main goal of this pilot study is to examine the role of vitamin D supplementation on AVF maturation and useability for dialysis. Study results will be used to develop larger studies to examine the specific effect that vitamin D supplementation has on the vessels used for AVF creation and whether vitamin D promotes AVF maturation.
Hemodialysis vascular access dysfunction is a major source of morbidity and cost among ESRD patients, accounting for up to 25% of all hospital stays, and 50% of all costs within the first year of initiating dialysis.The AVF provides higher blood flow rates, fewer thrombotic and infectious complications, and lower morbidity and cost compared with prosthetic grafts or central venous catheters.However,up to 50% of newly created AVF's fail to mature sufficiently for chronic hemodialysis use. Clearly, determining factors predictive of poor AVF maturation are important from both patient care and health policy perspectives and are worthy of investigation.
Vitamin D has antiproliferative, antioxidant and antiangiogenic properties. The observed association of vitamin D deficiency and increased risk of cardiovascular and peripheral vascular disease may extend to the vasculature used in the creation of an AVF.
As renal function worsens, patients with chronic kidney disease (CKD) produce less vitamin D, due to impaired renal conversion of 25-hydroxy- to 1,25-dihydroxyvitamin D by declining renal 1-alpha hydroxylase. As a result, at the time of dialysis initiation,78%-90% of ESRD patients are vitamin D deficient. Until recently, vitamin D deficiency among CKD and ESRD patients was only treated if hyperparathyroidism was present, however, more attention is now paid to nutritional vitamin D deficiency given its association with a range of comorbid conditions.Furthermore, 1,25-dihydroxyvitamin D and its analogue compounds are associated with improved survival in the CKD and ESRD populations. We believe that the observed benefits of vitamin D may improve AVF maturation among a population in which vitamin D deficiency is highly prevalent.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo | Placebo Comparator | Placebo one time per week for 3 weeks |
|
| Cholecalciferol | Experimental | Vitamin D 200,000 IU per week for 3 weeks |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Vitamin D3 | Drug | Vitamin D3 200,000 IU once a week for 3 weeks |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Arteriovenous Fistulae Maturation | Maturation of an AVF is the ability to stick the AVF with two large bore needles at ≥ 6 consecutive dialysis sessions, and achievement of an AVF blood flow >300 ml/min, assessed at six months following AVF creation. | 6 months |
| Measure | Description | Time Frame |
|---|---|---|
| 25-hydroxyvitamin D and Serum Calcium | 10 weeks |
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Inclusion Criteria
Exclusion Criteria
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| Name | Affiliation | Role |
|---|---|---|
| Haimanot Wasse, MD, MPH | Emory University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Emory University | Atlanta | Georgia | 30322 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 34298589 | Derived | Mohamed I, Kamarizan MFA, Da Silva A. Medical adjuvant treatment to increase patency of arteriovenous fistulae and grafts. Cochrane Database Syst Rev. 2021 Jul 23;7(7):CD002786. doi: 10.1002/14651858.CD002786.pub4. | |
| 24101420 | Derived | Wasse H, Huang R, Long Q, Zhao Y, Singapuri S, McKinnon W, Skardasis G, Tangpricha V. Very high-dose cholecalciferol and arteriovenous fistula maturation in ESRD: a randomized, double-blind, placebo-controlled pilot study. J Vasc Access. 2014 Mar-Apr;15(2):88-94. doi: 10.5301/jva.5000187. Epub 2013 Oct 7. |
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107 Assessed for Eligibility with 55 Excluded for declining to participate (12), not meeting criteria (41), and other reasons (6) leaving 52 patients randomly assigned for the study. Some individuals were counted as having more than two reasons to be excluded from the study.
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| ID | Title | Description |
|---|---|---|
| FG000 | Placebo | Placebo one time per week for 3 weeks |
| FG001 | Cholecalciferol | Vitamin D 200,000 IU per week for 3 weeks |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Placebo | Placebo one time per week for 3 weeks |
| BG001 | Cholecalciferol | Vitamin D 200,000 IU per week for 3 weeks |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| 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 | Arteriovenous Fistulae Maturation | Maturation of an AVF is the ability to stick the AVF with two large bore needles at ≥ 6 consecutive dialysis sessions, and achievement of an AVF blood flow >300 ml/min, assessed at six months following AVF creation. | Posted | Number | percentage of group | 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 | Placebo | Placebo one time per week for 3 weeks |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Monnie Wasse MD/MPH / Associate Professor of Medicine | Emory University | 404-727-1598 | hwasse@emory.edu |
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| ID | Term |
|---|---|
| D007676 | Kidney Failure, Chronic |
| ID | Term |
|---|---|
| D051436 | Renal Insufficiency, Chronic |
| D051437 | Renal Insufficiency |
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
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| ID | Term |
|---|---|
| D002762 | Cholecalciferol |
| ID | Term |
|---|---|
| D002782 | Cholestenes |
| D002776 | Cholestanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
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| Placebo |
| Drug |
Placebo one time per week for 3 weeks |
|
| 22237061 | Derived | Wasse H, Huang R, Long Q, Singapuri S, Raggi P, Tangpricha V. Efficacy and safety of a short course of very-high-dose cholecalciferol in hemodialysis. Am J Clin Nutr. 2012 Feb;95(2):522-8. doi: 10.3945/ajcn.111.025502. Epub 2012 Jan 11. |
| Did not receive vascular access type |
|
| Relocated before study completion |
|
| BG002 |
| Total |
Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Counts |
|---|
| Participants |
|
|
| Secondary | 25-hydroxyvitamin D and Serum Calcium | Posted | Mean | Standard Deviation | ng/mL | 10 weeks |
|
|
|
| 0 |
| 27 |
| 0 |
| 27 |
| EG001 | Cholecalciferol | Vitamin D 200,000 IU per week for 3 weeks | 0 | 25 | 0 | 25 |
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| D052776 |
| Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D011083 |
| Polycyclic Compounds |
| D013261 | Sterols |
| D014807 | Vitamin D |
| D012632 | Secosteroids |
| D008563 | Membrane Lipids |
| D008055 | Lipids |