Vitamin D in Ventilated ICU Patients

NCT ID: NCT01372995

Last Updated: 2017-01-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 31 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-07-31
• Study Completion Date: 2014-04-30

Brief Summary

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).

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.

Conditions

Respiratory Failure

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Enteral vitamin D3 50,000 IU

An arm where subjects receive 50,000 IU of Vitamin D for 5 days.

Group Type: EXPERIMENTAL

Enteral Vitamin D3 50,000 IU

Intervention Type: DRUG

Enteral Vitamin D3 50,000IU x 5 days (total dose 250,000IU)

Enteral Vitamin D3 100,000 IU

Arm where subjects receive 100,000 IU of Vitamin D for 5 days

Group Type: EXPERIMENTAL

Enteral Vitamin D3 100,000IU

Intervention Type: DRUG

Enteral Vitamin D3 100,000IU over 5 days (total 500,000IU)

Inactive Substance

Arm where patients receive inactive substance for 5 days.

Group Type: PLACEBO_COMPARATOR

Inactive substance

Intervention Type: OTHER

Inactive substance given enterally for 5 days.

Interventions

Enteral Vitamin D3 50,000 IU

Enteral Vitamin D3 50,000IU x 5 days (total dose 250,000IU)

Intervention Type: DRUG

Enteral Vitamin D3 100,000IU

Enteral Vitamin D3 100,000IU over 5 days (total 500,000IU)

Intervention Type: DRUG

Inactive substance

Inactive substance given enterally for 5 days.

Intervention Type: OTHER

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

Emory University

OTHER

Sponsor Role: lead

Responsible Party

Greg S. Martin, M.D., M.Sc.

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Greg Martin, MD, MSc

Role: PRINCIPAL_INVESTIGATOR

Emory University

Thomas Ziegler, MD

Role: PRINCIPAL_INVESTIGATOR

Emory University

Locations

Emory University Hospital Midtown

Atlanta, Georgia, United States

Emory University Hospital

Atlanta, Georgia, United States

Countries

United States

References

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Other Identifiers

IRB00049610

Identifier Type: -

Identifier Source: org_study_id