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Vitamin D in Ventilated ICU Patients (R21 HL-110044)

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by Emory University
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Greg S. Martin, M.D., M.Sc., Emory University
ClinicalTrials.gov Identifier:
NCT01372995
First received: June 13, 2011
Last updated: June 2, 2014
Last verified: June 2014
  Purpose

The increasing rate of hospital-acquired infection and antibiotic resistance are major causes of prolonged ICU stay and death in hospitalized patients. The enormous impact of ICU-related infection demands the need for cost-effective therapies that can be rapidly implemented to improve patient immune response to control infection. Unfortunately, little high-quality comparative effectiveness research has been performed on micronutrient treatment regimens as methods to decrease hospital-acquired infection in critically ill patients. Critically ill medical and surgical patients have an extremely high prevalence of vitamin D insufficiency.

We will perform a rigorous, double-blind, randomized, controlled, pilot clinical trial in ventilator-dependent ICU patients to test the clinical/metabolic safety and efficacy of two doses of oral high-dose vitamin D3 therapy versus standard therapy (no supplemental vitamin D). The primary endpoint is to test whether high-dose regimens [either 50,000 or 100,000 international units (IU) of enteral vitamin D3 given daily for 5 consecutive days (total dose = 250,000 or 500,000 IU, respectively) increase plasma 25(OH)D concentrations into a desirable range (> 30 ng/mL).


Condition Intervention Phase
Respiratory Failure
Dietary Supplement: Enteral Vitamin D3 50,000 IU
Dietary Supplement: Enteral Vitamin D3 100,000IU
Dietary Supplement: Inactive substance
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: High-Dose Vitamin D and Antimicrobial Peptide Expression in Lung Failure

Resource links provided by NLM:


Further study details as provided by Emory University:

Primary Outcome Measures:
  • To test whether two high-dose Vitamin D3 regimens given daily for 5 consecutive days increase plasma 25(OH)D concentrations into a desirable range (> 30 ng/mL). [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
    To perform a rigorous, double-blind, randomized, controlled, pilot clinical trial in ventilator-dependent ICU patients to test the clinical/metabolic safety and efficacy of two doses of oral high-dose vitamin D3 therapy versus standard therapy (no supplemental vitamin D). The primary endpoint is to test whether high-dose regimens [either 50,000 or 100,000 international units (IU) of enteral vitamin D3 given daily for 5 consecutive days (total dose = 250,000 or 500,000 IU, respectively) increase plasma 25(OH)D concentrations into a desirable range (> 30 ng/mL);


Secondary Outcome Measures:
  • To determine whether high-dose vitamin D treatment regimens increase antimicrobial peptide expression. [ Time Frame: 12 wks ] [ Designated as safety issue: No ]
    To determine, whether high-dose vitamin D treatment regimens increase LL-37 and hBD-2 concentrations in plasma and BAL fluid (by ELISA), cathelicidin and hBD-2 mRNA expression in PBMCs (by quantitative PCR), LL-37 and hBD-2 protein expression in alveolar macrophages (AM) (by immunohistochemistry), and ex vivo AM phagocytosis function.

  • To determine if high-dose vitamin D3 regimens decrease the overall incidence of ICU- and hospital-acquired infection [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
    To determine if high-dose vitamin D3 regimens decrease the overall incidence of ICU- and hospital-acquired infection (as a composite sum of all nosocomial infectious complications), reduce the occurrence of organ dysfunction (measured as SOFA score), and decrease the duration of mechanical ventilation and length of ICU and hospital stay.


Estimated Enrollment: 36
Study Start Date: July 2011
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Enteral vitamin D3 50,000 IU
An arm where subjects receive 50,000 IU of Vitamin D for 5 days.
Dietary Supplement: Enteral Vitamin D3 50,000 IU
Enteral Vitamin D3 50,000IU x 5 days (total dose 250,000IU)
Experimental: Enteral Vitamin D3 100,000 IU
Arm where subjects receive 100,000 IU of Vitamin D for 5 days
Dietary Supplement: Enteral Vitamin D3 100,000IU
Enteral Vitamin D3 100,000IU over 5 days (total 500,000IU)
Placebo Comparator: Inactive Substance
Arm where patients receive inactive substance for 5 days.
Dietary Supplement: Inactive substance
Inactive substance given enterally for 5 days.

Detailed Description:
  1. We will evaluate, over 12 weeks, the safety and efficacy of two high-dose vitamin D3 regimens in severely ill ICU patients. Vitamin D or placebo ( depending on study arm) will be given sequentially in divided doses for 5 days
  2. We will explore whether these vitamin D regimens are capable of increasing the production of key antimicrobial peptides LL-37 and hBD-2 ( substances produced by our bodies to fight infections), in both the blood and in lung.
  3. We will determine whether a higher vitamin D level in the blood is associated with a decrease in hospital infection rates and other complications in high-risk ICU patients with respiratory failure.

Study Design:

Enrollment goal is 36 patients. Once consent is obtained subjects will be randomly assigned to one of three study groups. Each group consists of 12 patients with enteral access ; a placebo arm, an arm where subjects receive 50,000 IU of Vitamin D for 5 days, and a third arm where subjects receive 100,000 IU of Vitamin D for 5 days.

Methods: Baseline blood samples (25-hydroxyvitamin D, vitamin D binding protein, ionized calcium, LL-37,and hBD-2) will be taken on study day 7,14,21,28,84 days. On study day 1 and 8, LL-37, hBD-2, cathelicidin from BAL fluid will also be analyzed. Patients will be given either placebo, Vitamin D3 50,000 IU x 5 days (total 250,000 IU) or Vitamin D3 100,000 IU x 5 days (total 500,000 IU) with an intention to treat model. Baseline data on the patients including demographic, laboratory, documented infections, severity illness score (APACHE II) and organ dysfunction score (SOFA) will be collected. ELISA assay on the serum and BAL will be performed.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Receiving care in an intensive care unit (ICU)
  • Age greater than 18 years
  • Expected to require mechanical ventilation for at least 72 hours after entry
  • Expected to survive and remain in the ICU for at least 96 hours after study entry
  • To enable delivery of study drug, the subject has enteral access in place and is deemed able to tolerate enteral drug administration

Exclusion Criteria:

  • Inability to obtain or declined informed consent from the subject and/or legally authorized representative
  • Pregnancy
  • Ongoing shock
  • Current hypercalcemia (albumin-corrected serum calcium > 10.8 mg/dL or ionized calcium > 5.2 mg/dL)
  • History of therapy with high-dose vitamin D to treat vitamin D deficiency within previous 6 months
  • History of disorders associated with hypercalcemia; history of cancer with history of hypercalcemia within the past 1 year, hyperparathyroidism, sarcoidosis, nephrolithiasis]
  • Chronic renal dysfunction requiring chronic dialysis
  • Known history of cirrhosis
  • History of AIDS
  • The patient has received any investigational drug within 60 days prior to study entry.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01372995

Contacts
Contact: Greg Martin, MD, MSc 404-616-0148 greg.martin@emory.edu
Contact: Jenny Han, MD jehan2@emory.edu

Locations
United States, Georgia
Emory University Hospital Recruiting
Atlanta, Georgia, United States, 30322
Contact: Greg Martin, MD, MSc    404-616-0148    greg.martin@emory.edu   
Contact: Jenny Han, MD    404-686-5500 ext 18600    jehan2@emory.edu   
Emory University Hospital Midtown Recruiting
Atlanta, Georgia, United States, 30308
Contact: Greg Martin, MD, MSc    404-616-0148    greg.martin@emory.edu   
Contact: Jenny Han, MD    404-686-5500 ext 18600    jehan2@emory.edu   
Sponsors and Collaborators
Emory University
Investigators
Principal Investigator: Greg Martin, MD, MSc Emory University
Principal Investigator: Thomas Ziegler, MD Emory University
  More Information

Publications:

Responsible Party: Greg S. Martin, M.D., M.Sc., Associate Professor, Emory University
ClinicalTrials.gov Identifier: NCT01372995     History of Changes
Other Study ID Numbers: IRB00049610
Study First Received: June 13, 2011
Last Updated: June 2, 2014
Health Authority: United States: Institutional Review Board
United States: Emory University IRB
United States: National Heart Lung and Blood Institute

Keywords provided by Emory University:
critical care
nosocomial infection
antiAntimicrobial peptide expression
LL-37
hBD-2
cathelicidin
microbial peptide

Additional relevant MeSH terms:
Respiratory Insufficiency
Respiration Disorders
Respiratory Tract Diseases
Cholecalciferol
Ergocalciferols
Vitamin D
Vitamins
Bone Density Conservation Agents
Growth Substances
Micronutrients
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on November 25, 2014