Impact of Vitamin D Repletion in Hemodialysis Patients

• Sponsor: Mehrotra, Anita, M.D. (Other)
• Overall Status: Completed
• CT.gov ID: NCT01175798
• Collaborator: National Kidney Foundation (Other), American Heart Association (Other)
• Enrollment: 116
• Location: 1
• Arms: 2
• Duration (Months): 36
• Patients Per Site Per Month: 3.2

Study Details

Study Description

Brief Summary

Dialysis patients often suffer from defects in their immune system (that part of the body which fights infection). Evidence suggests that Vitamin D deficiency may have a negative effect on immunity, and many dialysis patients are deficient in Vitamin D. We believe that by giving Vitamin D to dialysis patients who are deficient, we may help improve their immune system. This study will test that idea.

Condition or Disease	Intervention/Treatment	Phase
Vitamin D Deficiency; End-stage Renal Disease	Drug: Cholecalciferol	N/A

Detailed Description

Innate and adaptive immunity are commonly impaired in patients with end stage renal disease (ESRD) on dialysis. The myriad of immune defects in these patients, often attributed to uremia, may account for their high risk of bacterial infection and suboptimal responses to vaccination. The mechanisms underlying these abnormalities in immune function remain elusive, but emerging evidence indicates that 25OH-Vitamin D exerts potent and complex control over innate and adaptive immunity. Vitamin D deficiency is common in dialysis patients, and the immune effects associated with 25OH-Vit D deficiency overlap with those found in many dialysis patients. The kidney is the dominant site of 1-alpha-hydroxylase activity required for producing active 1,25OH-Vit D; however, immune cells also express the 1-alpha-hydroxylase enzyme. Evidence indicates the effects of Vitamin D on modulating immunity require conversion of 25OH-Vit D to 1,25OH-Vit D within the immune cells (rather than via circulating 1,25OH-Vit D). As a consequence, total body deficiency of 25OH-Vit D can impact immune function despite ongoing therapy with active 1,25OH-Vit D (which most dialysis patients are receiving). Our preliminary data confirm the high prevalence of 25OH-Vit D deficiency in dialysis patients and show that Th1 T cell alloimmunity is stronger in patients deficient in 25OH-Vit D, supporting the hypothesis that Vit D deficiency has important immunological consequences. Based on the published literature and our preliminary data, we hypothesize that repletion of 25OH-Vit D enhances immunity in dialysis patients. To test this hypothesis, we propose a randomized controlled trial of oral 25OH-Vit D repletion in this patient population. One hundred fifty 25OH-Vit D deficient study subjects will be randomized to either treatment with 50,000 IU oral 25OH-Vit D weekly or no treatment (standard of care). The primary outcome of change in 25OH-Vit D level will be measured at 6 weeks, 3 months, 6 months, and 12 months. Secondary outcomes to be measured include change in peripheral blood mononuclear cell (PBMC) profile by flow cytometry at 6 and 12 months, change in ELISPOT-based panel of reactive T cell (PRT) readout at 6 and 12 months, change in PMBC cytokine production in response to toll-like-receptor stimulation at 6 and 12 months, and response to influenza vaccination.

Study Design

• Study Type: Interventional
• Actual Enrollment: 116 participants
• Allocation: Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Immunologic Impact of Vitamin D Repletion in Hemodialysis Patients: A Randomized Controlled Trial
• Study Start Date: Aug 1, 2010
• Actual Primary Completion Date: Aug 1, 2013
• Actual Study Completion Date: Aug 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
No Intervention: No treatment (standard of care) Patients will be randomized in a 3:2 ratio to oral Vitamin D treatment, or standard of care (no repletion).
Experimental: Vitamin D repletion Patients will be randomized in a 3:2 ratio to oral Vitamin D treatment, or standard of care (no repletion).	Drug: Cholecalciferol; 50,000 IU PO weekly x 6 weeks; Other Names: Vitamin D

Outcome Measures

Primary Outcome Measures

1. Change in 25OH-Vitamin D Level [1 year]

   Vitamin D deficient study subjects will be randomized to either treatment with 50,000 IU oral 25OH-Vit D weekly or no treatment (standard of care). The primary outcome of change in 25OH-Vit D level will be measured at 6 weeks, 3 months, 6 months, and 12 months.

Secondary Outcome Measures

1. Change in Immune Parameters [1 year]

   Secondary outcomes to be measured include change in peripheral blood mononuclear cell (PBMC) profile by flow cytometry at 6 and 12 months, change in ELISPOT-based panel of reactive T cell (PRT) readout at 6 and 12 months, change in PMBC cytokine production in response to toll-like-receptor stimulation at 6 and 12 months, and response to influenza vaccination.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Age > 18 years

2. Chronic hemodialysis treatments for at least 2 consecutive months

3. 25OH-Vitamin D level < 25 ng/mL (inclusion criteria for randomization)

Exclusion Criteria:

1. History of acute renal failure requiring dialysis with potential for renal recovery

2. History of HIV/AIDS

3. Inability to provide informed consent

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mount Sinai School of Medicine	New York	New York	United States	10029

Sponsors and Collaborators

• Mehrotra, Anita, M.D.
• National Kidney Foundation
• American Heart Association

Investigators

• Principal Investigator: Anita Mehrotra, MD, Icahn School of Medicine at Mount Sinai

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Anita Mehrotra MD, Principal Investigator, Icahn School of Medicine at Mount Sinai
• ClinicalTrials.gov Identifier: NCT01175798
• Other Study ID Numbers: 09-2275
• First Posted: Aug 5, 2010
• Last Update Posted: Sep 22, 2014
• Last Verified: Sep 1, 2014

• Keywords provided by Anita Mehrotra MD, Principal Investigator, Icahn School of Medicine at Mount Sinai: Vitamin D deficiency; End-stage renal disease; Immunity
• Additional relevant MeSH terms: Kidney Diseases; Kidney Failure, Chronic; Vitamin D Deficiency; Vitamin D; Cholecalciferol

Study Results

Participant Flow

Arm/Group Title	No Treatment (Standard of Care)	Vitamin D Repletion
Arm/Group Description	Patients will be randomized in a 3:2 ratio to oral Vitamin D treatment, or standard of care (no repletion).	Patients will be randomized in a 3:2 ratio to oral Vitamin D treatment, or standard of care (no repletion). Cholecalciferol: 50,000 IU PO weekly x 6 weeks
Period Title: Overall Study
STARTED	34	62
COMPLETED	27	41
NOT COMPLETED	7	21

Baseline Characteristics

Arm/Group Title	No Treatment (Standard of Care)	Vitamin D Repletion	Total
Arm/Group Description	Patients will be randomized in a 3:2 ratio to oral Vitamin D treatment, or standard of care (no repletion).	Patients will be randomized in a 3:2 ratio to oral Vitamin D treatment, or standard of care (no repletion). Cholecalciferol: 50,000 IU PO weekly x 6 weeks	Total of all reporting groups
Overall Participants	34	62	96
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	58.9 (14.9)	60.2 (14.3)	59 (15)
Sex: Female, Male (Count of Participants)
Female	14 41.2%	26 41.9%	40 41.7%
Male	20 58.8%	36 58.1%	56 58.3%
25(OH) vitamin D (ng/dL) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [ng/dL]	13.1	13.4	13.2

Outcome Measures

1. Primary Outcome

Title	Change in 25OH-Vitamin D Level
Description	Vitamin D deficient study subjects will be randomized to either treatment with 50,000 IU oral 25OH-Vit D weekly or no treatment (standard of care). The primary outcome of change in 25OH-Vit D level will be measured at 6 weeks, 3 months, 6 months, and 12 months.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	No Treatment (Standard of Care)	Vitamin D Repletion
Arm/Group Description	Patients will be randomized in a 3:2 ratio to oral Vitamin D treatment, or standard of care (no repletion).	Patients will be randomized in a 3:2 ratio to oral Vitamin D treatment, or standard of care (no repletion). Cholecalciferol: 50,000 IU PO weekly x 6 weeks
Measure Participants	27	41
Median (Inter-Quartile Range) [ng/dL]	15.8	40.9

2. Secondary Outcome

Title	Change in Immune Parameters
Description	Secondary outcomes to be measured include change in peripheral blood mononuclear cell (PBMC) profile by flow cytometry at 6 and 12 months, change in ELISPOT-based panel of reactive T cell (PRT) readout at 6 and 12 months, change in PMBC cytokine production in response to toll-like-receptor stimulation at 6 and 12 months, and response to influenza vaccination.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Arm/Group Title	No Treatment (Standard of Care)		Vitamin D Repletion
Arm/Group Description	Patients will be randomized in a 3:2 ratio to oral Vitamin D treatment, or standard of care (no repletion).		Patients will be randomized in a 3:2 ratio to oral Vitamin D treatment, or standard of care (no repletion). Cholecalciferol: 50,000 IU PO weekly x 6 weeks
All Cause Mortality
	No Treatment (Standard of Care)		Vitamin D Repletion
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	No Treatment (Standard of Care)		Vitamin D Repletion
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/34 (0%)		0/62 (0%)
Other (Not Including Serious) Adverse Events
	No Treatment (Standard of Care)		Vitamin D Repletion
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/34 (0%)		0/62 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.