Vitamin D Supplementation in Kidney Disease

Study Overview
=================
Brief Summary
-----------------
This is a double-blind placebo controlled pilot study to determine if vitamin D supplementation in hemodialysis (HD) patients will improve physical function and cognition. HD patients have a high prevalence of vitamin D deficiency, cognitive impairment, and physical impairment. Despite standard clinical care with active IV vitamin D during dialysis, HD patients still have markedly low levels of nutritional or dietary vitamin D. IV treatment with vitamin D during dialysis is aimed at treating HD related bone disease. Recent literature shows that oral or nutritional vitamin D has multiple extra-skeletal effects including improvement in cognition and physical function. In this study, the investigators plan to administer oral vitamin D to vitamin D deficient HD patients already receiving standard care with IV vitamin D therapy. Patients will be randomized to receive either placebo or 50,000 IU of vitamin D (cholecalciferol) weekly for 6 months. The investigators' specific aims are to 1) Assess the benefits of correcting nutritional vitamin D deficiency on cognitive and physical function in HD patients receiving routine standard of care, 2) Assess the feasibility of recruiting HD patients for this study, and 3) Evaluate the proposed regimen for safely and effectively increasing nutritional vitamin D levels with oral supplementation. The investigators anticipate that correction of nutritional vitamin D deficiency to optimal levels will improve the high prevalence of cognitive impairment and physical impairment in this population. These results will be used as evidence to support a larger study aimed at treating nutritional vitamin D deficiency in all patients receiving HD. These results may also contribute to a change in current guidelines which place little emphasis on the monitoring and treatment of nutritional vitamin D levels in HD patients. These results are important for the Veteran dialysis population since many of them are required to perform high-level cognitive tasks such as management of complex medical regimens and physical tasks such as orchestrating independent transportation to and from HD sessions and multiple physician appointments.

Detailed Description
-----------------
Patients will first be identified based on the inclusion criteria, then informed about the study and consented. Those who meet the exclusion criteria will be randomized to treatment or placebo. Enrolled participants will be randomized 2:1 to receive vitamin D (n=20) or placebo (n=10) for 6 months. All participants will be tested twice over two weeks to establish baseline values. Following baseline testing, the treatment group will receive 50,000 IU (standard replacement therapy) of oral cholecalciferol or placebo. The initial dose of cholecalciferol will be 50,000 IU weekly for 6 weeks. Vitamin D levels will then be measured. Participants who still have Vitamin D insufficiency ( 35 ng/ml) will remain on 50,000 IU of cholecalciferol for another 6 weeks, at which point Vitamin D levels will be measured again. Participants who reach 25-OH levels > 35 ng/ml will have their dosing regimen lessened to 10,000 IU weekly (maintenance dose) for the remainder of the 6 months. Participants receiving placebo will start taking the placebo maintenance dose after the first 6 weeks. For safety monitoring, 25(OH) vitamin D3 levels will also be re-measured at monthly intervals and followed by an independent medical monitor. In patients who have serum vitamin D levels 60ng/ml, the frequency of administration will be reduced to once a month. The participants will receive supplementation for a total of 6 months. At this time, vitamin D levels will be reassessed and participants will undergo follow-up functional assessments, and cognitive and immune testing.

Official Title
-----------------
Vitamin D Supplementation on Physical and Cognitive Function-Pilot Study

Conditions
-----------------
Renal Dialysis, Vitamin D Deficiency

Intervention / Treatment
-----------------
* Dietary Supplement: Cholecalciferol (Vitamin D)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Receiving HD for at least two weeks Receiving IV vitamin D supplementation according to National Kidney Foundation guidelines. Male or female with an between the ages of 45-89 years Veteran outpatient or stable community living center patient Able to ambulate independently or with an assistive device for at least 20 feet Exclusion Criteria: 25-OH vitamin D level < 25 ng/ml Hypercalcemia Active malignancy within 6 months Receiving intravenous antibiotics for infection History of Dementia Hemoglobin < 8.5g History of conditions that interfere with postural instability (e.g. cerebellar disease, vestibular disease or any others that may present) Poor compliance with dialysis treatments (history of skipping 2 treatments per month for > 2 months)

Ages Eligible for Study
-----------------
Minimum Age: 45 Years
Maximum Age: 89 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm 1<br>Hemodialysis Patients randomized to take Vitamin D supplements | Dietary Supplement: Cholecalciferol (Vitamin D)<br>* 50,000 units of cholecalciferol or a placebo pill administered once a week for 6 months<br>|
| Placebo Comparator: Arm 2<br>Hemodialysis Patients randomized to take placebo pills | Dietary Supplement: Cholecalciferol (Vitamin D)<br>* 50,000 units of cholecalciferol or a placebo pill administered once a week for 6 months<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neuromuscular Function | strength testing of hip flexors and extensors | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality-of-Life self assessment | questionnaire of physical/medical health | 6 months | 
| Neuropsychological assessments | battery of neurocognitive tests | 6 months | 
| Immune Function assessments | assay of immunity markers | 6 months |