Vitamin D in Ventilated ICU Patients

NCT01372995 | Completed Phase 2 Results DMC

• 1 other identifier: IRB00049610
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 2

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).

Conditions

Respiratory Failure

Keywords

critical care; nosocomial infection; antiAntimicrobial peptide expression; LL-37; hBD-2; cathelicidin; microbial peptide

Outcome Measures

Primary Outcomes (6)

• Number of Participants With Plasma 25(OH)D Concentration >30ng/mL at 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

  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

  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

  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

  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

  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 Outcomes (8)

• Change in Plasma LL-37 Levels

  Baseline, Day 7, Day 14

• Duration of Time on Ventilator

  12 weeks

• Duration of Time in Intensive Care Unit (ICU)

  12 weeks

• Duration of Time in Hospital

  12 weeks

• Change in Sequential Organ Failure Assessment (SOFA) Score

  Baseline, Day 7

Study Arms (3)

Enteral vitamin D3 50,000 IU

EXPERIMENTAL

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

Drug: Enteral Vitamin D3 50,000 IU

Enteral Vitamin D3 100,000 IU

EXPERIMENTAL

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

Drug: Enteral Vitamin D3 100,000IU

Inactive Substance

PLACEBO COMPARATOR

Arm where patients receive inactive substance for 5 days.

Other: Inactive substance

Interventions

Enteral Vitamin D3 50,000 IU DRUG

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

Enteral vitamin D3 50,000 IU

Enteral Vitamin D3 100,000IU DRUG

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

Enteral Vitamin D3 100,000 IU

Inactive substance OTHER

Inactive substance given enterally for 5 days.

Inactive Substance

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Emory University: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (2)

Emory University Hospital Midtown

Atlanta, Georgia, 30308, United States

Location

Emory University Hospital

Atlanta, Georgia, 30322, United States

Location

Related Publications (9)

• Tejada Artigas A, Bello Dronda S, Chacon Valles E, Munoz Marco J, Villuendas Uson MC, Figueras P, Suarez FJ, Hernandez A. Risk factors for nosocomial pneumonia in critically ill trauma patients. Crit Care Med. 2001 Feb;29(2):304-9. doi: 10.1097/00003246-200102000-00015.

  PMID: 11246310 BACKGROUND

• Winther B, Greve JM, Gwaltney JM Jr, Innes DJ, Eastham JR, McClelland A, Hendley JO. Surface expression of intercellular adhesion molecule 1 on epithelial cells in the human adenoid. J Infect Dis. 1997 Aug;176(2):523-5. doi: 10.1086/517280.

  PMID: 9237723 BACKGROUND

• Urashima M, Segawa T, Okazaki M, Kurihara M, Wada Y, Ida H. Randomized trial of vitamin D supplementation to prevent seasonal influenza A in schoolchildren. Am J Clin Nutr. 2010 May;91(5):1255-60. doi: 10.3945/ajcn.2009.29094. Epub 2010 Mar 10.

  PMID: 20219962 BACKGROUND

• Manaseki-Holland S, Qader G, Isaq Masher M, Bruce J, Zulf Mughal M, Chandramohan D, Walraven G. Effects of vitamin D supplementation to children diagnosed with pneumonia in Kabul: a randomised controlled trial. Trop Med Int Health. 2010 Oct;15(10):1148-55. doi: 10.1111/j.1365-3156.2010.02578.x. Epub 2010 Aug 17.

  PMID: 20723187 BACKGROUND

• Yim S, Dhawan P, Ragunath C, Christakos S, Diamond G. Induction of cathelicidin in normal and CF bronchial epithelial cells by 1,25-dihydroxyvitamin D(3). J Cyst Fibros. 2007 Nov 30;6(6):403-10. doi: 10.1016/j.jcf.2007.03.003. Epub 2007 Apr 27.

  PMID: 17467345 BACKGROUND

• De Smet K, Contreras R. Human antimicrobial peptides: defensins, cathelicidins and histatins. Biotechnol Lett. 2005 Sep;27(18):1337-47. doi: 10.1007/s10529-005-0936-5.

  PMID: 16215847 BACKGROUND

• Barlow PG, Beaumont PE, Cosseau C, Mackellar A, Wilkinson TS, Hancock RE, Haslett C, Govan JR, Simpson AJ, Davidson DJ. The human cathelicidin LL-37 preferentially promotes apoptosis of infected airway epithelium. Am J Respir Cell Mol Biol. 2010 Dec;43(6):692-702. doi: 10.1165/rcmb.2009-0250OC. Epub 2010 Jan 22.

  PMID: 20097832 BACKGROUND

• Jeng L, Yamshchikov AV, Judd SE, Blumberg HM, Martin GS, Ziegler TR, Tangpricha V. Alterations in vitamin D status and anti-microbial peptide levels in patients in the intensive care unit with sepsis. J Transl Med. 2009 Apr 23;7:28. doi: 10.1186/1479-5876-7-28.

  PMID: 19389235 BACKGROUND

• Han JE, Jones JL, Tangpricha V, Brown MA, Brown LAS, Hao L, Hebbar G, Lee MJ, Liu S, Ziegler TR, Martin GS. High Dose Vitamin D Administration in Ventilated Intensive Care Unit Patients: A Pilot Double Blind Randomized Controlled Trial. J Clin Transl Endocrinol. 2016 Jun;4:59-65. doi: 10.1016/j.jcte.2016.04.004. Epub 2016 May 5.

  PMID: 27419080 DERIVED

MeSH Terms

Conditions

Respiratory Insufficiency; Cross Infection

Condition Hierarchy (Ancestors)

Respiration Disorders; Respiratory Tract Diseases; Infections; Iatrogenic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

Limitations to generalizability of this pilot study include the small sample size and imbalances in chronic conditions between treatment arms at study entry.

Results Point of Contact

• Title: Jenny Han, MD
• Organization: Emory University

jehan2@emory.edu

404-616-0821

Study Officials

• Greg Martin, MD, MSc

  Emory University

  PRINCIPAL INVESTIGATOR

• Thomas Ziegler, MD

  Emory University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: June 13, 2011
• First Posted: June 14, 2011
• Study Start: July 1, 2011
• Primary Completion: April 1, 2014
• Study Completion: April 1, 2014
• Last Updated: January 9, 2017
• Results First Posted: January 9, 2017

Record last verified: 2016-11

Locations

US (2)