Vitamin D in Ventilated ICU Patients (R21 HL-110044)
10 de noviembre de 2016 actualizado por: 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).
Descripción general del estudio
Estado
Terminado
Condiciones
Intervención / Tratamiento
Descripción detallada
- 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
- 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.
- 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.
Tipo de estudio
Intervencionista
Inscripción (Actual)
31
Fase
- Fase 2
Contactos y Ubicaciones
Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.
Ubicaciones de estudio
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Georgia
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Atlanta, Georgia, Estados Unidos, 30322
- Emory University Hospital
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Atlanta, Georgia, Estados Unidos, 30308
- Emory University Hospital Midtown
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Criterios de participación
Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.
Criterio de elegibilidad
Edades elegibles para estudiar
18 años y mayores (Adulto, Adulto Mayor)
Acepta Voluntarios Saludables
No
Géneros elegibles para el estudio
Todos
Descripción
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.
Plan de estudios
Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Cuadruplicar
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
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Experimental: Enteral vitamin D3 50,000 IU
An arm where subjects receive 50,000 IU of Vitamin D for 5 days.
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Enteral Vitamin D3 50,000IU x 5 days (total dose 250,000IU)
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Experimental: Enteral Vitamin D3 100,000 IU
Arm where subjects receive 100,000 IU of Vitamin D for 5 days
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Enteral Vitamin D3 100,000IU over 5 days (total 500,000IU)
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Comparador de placebos: Inactive Substance
Arm where patients receive inactive substance for 5 days.
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Inactive substance given enterally for 5 days.
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Number of Participants With Plasma 25(OH)D Concentration >30ng/mL at Baseline
Periodo de tiempo: Baseline
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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.
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Baseline
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Number of Participants With Plasma 25(OH)D Concentration >30ng/mL at Day 7
Periodo de tiempo: Day 7
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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.
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Day 7
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Number of Participants With Plasma 25(OH)D Concentration >30ng/mL at Day 14
Periodo de tiempo: Day 14
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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.
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Day 14
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Number of Participants With Plasma 25(OH)D Concentration >30ng/mL at Day 21
Periodo de tiempo: Day 21
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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.
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Day 21
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Number of Participants With Plasma 25(OH)D Concentration >30ng/mL at Day 28
Periodo de tiempo: Day 28
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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.
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Day 28
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Number of Participants With Plasma 25(OH)D Concentration >30ng/mL at Day 84
Periodo de tiempo: Day 84
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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.
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Day 84
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Change in Plasma LL-37 Levels
Periodo de tiempo: Baseline, Day 7, Day 14
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Plasma LL-37 was measured at Baseline, Day 7 and Day 14.
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Baseline, Day 7, Day 14
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Duration of Time on Ventilator
Periodo de tiempo: 12 weeks
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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.
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12 weeks
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Duration of Time in Intensive Care Unit (ICU)
Periodo de tiempo: 12 weeks
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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.
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12 weeks
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Duration of Time in Hospital
Periodo de tiempo: 12 weeks
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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.
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12 weeks
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Change in Sequential Organ Failure Assessment (SOFA) Score
Periodo de tiempo: Baseline, Day 7
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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.
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Baseline, Day 7
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Number of Hospital Acquired Infections
Periodo de tiempo: 12 weeks
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The number of study participants who had a hospital acquired infection.
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12 weeks
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Number of Hospital Mortality Cases
Periodo de tiempo: 12 weeks
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The number of study participants who died while in the hospital was collected.
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12 weeks
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Day 84 Mortality
Periodo de tiempo: Day 84
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The number of participants who died prior to the end of the study (Day 84) was collected.
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Day 84
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Colaboradores e Investigadores
Aquí es donde encontrará personas y organizaciones involucradas en este estudio.
Patrocinador
Colaboradores
Investigadores
- Investigador principal: Thomas Ziegler, MD, Emory University
- Investigador principal: Greg Martin, MD, MSc, Emory University
Publicaciones y enlaces útiles
La persona responsable de ingresar información sobre el estudio proporciona voluntariamente estas publicaciones. Estos pueden ser sobre cualquier cosa relacionada con el estudio.
Publicaciones Generales
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
Fechas de registro del estudio
Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.
Fechas importantes del estudio
Inicio del estudio
1 de julio de 2011
Finalización primaria (Actual)
1 de abril de 2014
Finalización del estudio (Actual)
1 de abril de 2014
Fechas de registro del estudio
Enviado por primera vez
13 de junio de 2011
Primero enviado que cumplió con los criterios de control de calidad
13 de junio de 2011
Publicado por primera vez (Estimar)
14 de junio de 2011
Actualizaciones de registros de estudio
Última actualización publicada (Estimar)
9 de enero de 2017
Última actualización enviada que cumplió con los criterios de control de calidad
10 de noviembre de 2016
Última verificación
1 de noviembre de 2016
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
- IRB00049610
Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .
Ensayos clínicos sobre Enteral Vitamin D3 50,000 IU
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Aalborg UniversityAalborg University Hospital; CCBR Aalborg A/S, Aalborg, DenmarkTerminadoMigraña según los criterios de la International Headache Society (IHS) (ICHD-II)Dinamarca