Vitamin D in Ventilated ICU Patients
| Status: | Completed |
|---|---|
| Conditions: | Pulmonary |
| Therapuetic Areas: | Pulmonary / Respiratory Diseases |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 2/7/2015 |
| Start Date: | July 2011 |
| End Date: | December 2014 |
| Contact: | Greg Martin, MD, MSc |
| Email: | greg.martin@emory.edu |
| Phone: | 404-616-0148 |
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).
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).
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.
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.
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.
We found this trial at
2
sites
Emory University Hospital Midtown Emory University Hospital Midtown is a 511-bed community-based, acute care teaching...
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Emory University Hospital As the largest health care system in Georgia and the only health...
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