Vitamin D Supplementation And Varicella Zoster Virus Vaccine Responsiveness In Older Long-Term Care Residents

Vitamin D Supplementation And Varicella Zoster Virus Vaccine Responsiveness In Older Nursing Home Residents

This is an ancillary study to a randomized controlled trial of high dose vitamin D in older long-term care residents (NCT01102374). In this study, a subset of trial subjects will receive the zoster vaccine and the investigators will determine the immunological response to the vaccine in this older, frail population, as well as the association between vitamin D and immunological outcomes.

Study Overview

• Status: Completed
• Conditions: Immunosenescence; Shingles
• Intervention / Treatment: Biological: Varicella Zoster Virus Vaccine (Zostavax)

Detailed Description

Objectives

1. To determine the increase in Varicella-zoster virus (VZV)-specific cell-mediated immune response from pre-zoster vaccination to 3 weeks post-vaccination in nursing home residents after 4 months of high dose vs. standard dose vitamin D3 supplementation.
2. In the same participants as Aim 1, to measure the association between pre-zoster vaccination 25-hydroxyvitamin D [25(OH)D] levels and the increase in VZV-specific cell-mediated immune response from pre- vaccination to 3 weeks post-vaccination.
3. Characterize the phenotypic and functional VZV-specific T cell responses to Zostavax, including memory, effector, Th1/Th2, and homing receptor-bearing T cells in the high compared to low ELISPOT responders.

Hypotheses

1. At baseline, higher serum 25(OH)D levels will be associated with higher levels of VZV-specific cell-mediated immunity (cross-sectional).
2. At baseline, higher serum 25(OH)D levels, independent of vitamin D supplementation dose, will be associated with greater increases in VZV-specific cell-mediated immune responses to Zostavax, as measured by the interferon (IFN)-γ ELISPOT assay.
3. Compared to standard dose, high dose vitamin D3 supplementation will enhance VZV-specific cell-mediated immune response to vaccination independent of baseline serum 25(OH)D levels.

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Denver

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Aged ≥ 60 years;
2. Residing in a long-term care facility;
3. Have not yet received VZV vaccine

Exclusion Criteria:

1. terminal illness (expected survival <6 months);
2. anticipated discharge within 12 months;
3. unable to take whole or crushed tablets;
4. active cancer, except squamous/basal cell carcinoma;
5. severe malnutrition (body mass index <18 kg/m2);
6. current immunosuppressive medications (including corticosteroids);
7. renal failure (eGFR<15 mL/min/1.73m2);
8. currently taking >800 IU/d vitamin D supplementation;
9. history (or strong family history) of kidney stones;
10. history of sarcoidosis or other granulomatous disorders associated with hypercalcemia;
11. elevated baseline hypercalcemia (albumin-adjusted serum calcium >10.5 mg/dL);
12. serum 25 (OH)D level ≥40 ngl/ml at baseline;
13. inability to provide informed consent and no available healthcare proxy;
14. inability of participant or proxy to speak/understand English.
15. previous receipt of the Zostavax (anticipate <10% of trial;
16. known allergy to gelatin, neomycin, or any other component of the vaccine.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: VZV vaccine; Varicella Zoster Virus vaccine (Zostavax), single dose X 1 injection All subjects in this trial will receive the VZV vaccine. The Investigators will primarily compare immune responses in those that are receiving high dose vs. standard dose vitamin D supplementation and those that have high and low 25-hydroxyvitamin D levels.	Biological: Varicella Zoster Virus Vaccine (Zostavax); Single 0.65 mL subcutaneous injection of the live, attenuated VZV zoster vaccine (Zostavax; Merck, Whitehouse Station, NJ).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
VZV-specific cell mediated immunity, as measured by the interferon-γ ELISPOT assay	3 weeks post-vaccination

Secondary Outcome Measures

Outcome Measure	Time Frame
VZV-gpELISA to measure the VZV-specific antibody concentration	3 weeks post-vaccination
VZV-specific effector and memory T cells	3 weeks post-vaccination
-specific cell mediated immunity, as measured by the responder cell frequency assay	3 weeks post-vaccination

Collaborators and Investigators

• Sponsor: University of Colorado, Denver
• Collaborators: Merck Sharp & Dohme LLC; National Institute on Aging (NIA)

Publications and helpful links

General Publications

• A randomized controlled trial of high dose vitamin D in older long-term care residents (NCT01102374)

Study record dates

Study Major Dates

• Study Start: November 1, 2010
• Primary Completion (Actual): January 23, 2014
• Study Completion (Actual): January 23, 2014

Study Registration Dates

• First Submitted: December 15, 2010
• First Submitted That Met QC Criteria: December 15, 2010
• First Posted (Estimate): December 17, 2010

Study Record Updates

• Last Update Posted (Actual): June 25, 2021
• Last Update Submitted That Met QC Criteria: June 23, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: Vitamin D; Vaccine; Immunosenescence; Immune Response; Geriatrics; Shingles; Varicella Zoster Virus
• Additional Relevant MeSH Terms: Virus Diseases; Infections; DNA Virus Infections; Herpesviridae Infections; Varicella Zoster Virus Infection; Herpes Zoster; Chickenpox
• Other Study ID Numbers: 10-0189; K23AG040708 (U.S. NIH Grant/Contract)