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

November 10, 2016 updated by: Greg S. Martin, M.D., M.Sc., Emory University

High-Dose Vitamin D and Antimicrobial Peptide Expression in Lung Failure

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).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

31

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Emory University Hospital
      • Atlanta, Georgia, United States, 30308
        • Emory University Hospital Midtown

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Enteral vitamin D3 50,000 IU
An arm where subjects receive 50,000 IU of Vitamin D for 5 days.
Drug: 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
Drug: 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.
Other: Inactive substance
Inactive substance given enterally for 5 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Plasma 25(OH)D Concentration >30ng/mL at Baseline
Time Frame: Baseline
The number of participants with a plasma 25(OH)D concentration in the desirable range (defined as greater than 30 ng/mL) at the baseline measurement.
Baseline
Number of Participants With Plasma 25(OH)D Concentration >30ng/mL at Day 7
Time Frame: Day 7
The number of participants with a plasma 25(OH)D concentration in the desirable range (defined as greater than 30 ng/mL) at the Day 7 measurement.
Day 7
Number of Participants With Plasma 25(OH)D Concentration >30ng/mL at Day 14
Time Frame: Day 14
The number of participants with a plasma 25(OH)D concentration in the desirable range (defined as greater than 30 ng/mL) at the Day 14 measurement.
Day 14
Number of Participants With Plasma 25(OH)D Concentration >30ng/mL at Day 21
Time Frame: Day 21
The number of participants with a plasma 25(OH)D concentration in the desirable range (defined as greater than 30 ng/mL) at the Day 21 measurement.
Day 21
Number of Participants With Plasma 25(OH)D Concentration >30ng/mL at Day 28
Time Frame: Day 28
The number of participants with a plasma 25(OH)D concentration in the desirable range (defined as greater than 30 ng/mL) at the Day 28 measurement.
Day 28
Number of Participants With Plasma 25(OH)D Concentration >30ng/mL at Day 84
Time Frame: Day 84
The number of participants with a plasma 25(OH)D concentration in the desirable range (defined as greater than 30 ng/mL) at the Day 84 measurement.
Day 84

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Plasma LL-37 Levels
Time Frame: Baseline, Day 7, Day 14
Plasma LL-37 was measured at Baseline, Day 7 and Day 14.
Baseline, Day 7, Day 14
Duration of Time on Ventilator
Time Frame: 12 weeks
The number of days spent on mechanical ventilation was collected for all study participants and the average number of days for each study arm is reported.
12 weeks
Duration of Time in Intensive Care Unit (ICU)
Time Frame: 12 weeks
The number of days spent in the intensive care unit (ICU) was collected for each participant and the average number of days for each study arm is reported.
12 weeks
Duration of Time in Hospital
Time Frame: 12 weeks
The number of days that each participant spent in the hospital was collected and the average number of days for each study arm is reported.
12 weeks
Change in Sequential Organ Failure Assessment (SOFA) Score
Time Frame: Baseline, Day 7
Change in Sequential Organ Failure Assessment (SOFA) score between Baseline and Day 7. The Sequential Organ Failure Assessment (SOFA) score is a mortality prediction score that is based on the degree of dysfunction of 6 organ systems (respiratory, nervous, cardiovascular, liver, coagulation, and kidneys). A score ranges from 0-24. 0 (normal) to 4 (high degree of dysfunction) is given for each organ system, with a higher score indicating greater severity. A score of 0-6 is associated with a mortality rate of less than 10% while a score between 16 and 24 is associated with a greater than 90% mortality rate. Scores decreasing between the Baseline and Day 7 measurements are represented as negative values for the change in SOFA score.
Baseline, Day 7
Number of Hospital Acquired Infections
Time Frame: 12 weeks
The number of study participants who had a hospital acquired infection.
12 weeks
Number of Hospital Mortality Cases
Time Frame: 12 weeks
The number of study participants who died while in the hospital was collected.
12 weeks
Day 84 Mortality
Time Frame: Day 84
The number of participants who died prior to the end of the study (Day 84) was collected.
Day 84

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Emory University

Collaborators

National Heart, Lung, and Blood Institute (NHLBI)

Investigators

  • Principal Investigator: Thomas Ziegler, MD, Emory University
  • Principal Investigator: Greg Martin, MD, MSc, Emory University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2011

Primary Completion (Actual)

April 1, 2014

Study Completion (Actual)

April 1, 2014

Study Registration Dates

First Submitted

June 13, 2011

First Submitted That Met QC Criteria

June 13, 2011

First Posted (Estimate)

June 14, 2011

Study Record Updates

Last Update Posted (Estimate)

January 9, 2017

Last Update Submitted That Met QC Criteria

November 10, 2016

Last Verified

November 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IRB00049610

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Respiratory Failure

Clinical Trials on Enteral Vitamin D3 50,000 IU

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Denmark

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe