Therapeutic Benefit of Preoperative Supplemental Vitamin D in Patients Undergoing Major Surgical Procedures.

NCT02138591 | Withdrawn Phase 3

• 1 other identifier: 14-149
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

Vitamin D (Vitamin D) deficiency is very common. We recently showed that 97% of 204 patients admitted to Truman Medical Center were Vitamin D deficient (\<30 ng/ml). However, the consequences of Vitamin D deficiency, particularly with respect to infection, are not well understood. It is known that production of cathelicidin, an important antimicrobial peptide, is critically dependent upon Vitamin D. It is also established that levels of cathelicidin correlate inversely with urinary tract infection risk. We hypothesize that restoration of Vitamin D levels to normal in patients undergoing major surgery will result in significant decreases in levels of perioperative infections due to restoration of normal levels of circulating Vitamin D, which in turn will elevate cathelicidin levels. As an initial test of this hypothesis, we propose a double-blind, prospective, randomized study of pre-operative Vitamin D supplementation. Fifty subjects undergoing surgery will receive daily Vitamin D3 (50,000 IU) for five days pre-operatively, with controls receiving placebo. Levels of Vitamin D, calcium, cathelicidin, and the pro-inflammatory protein resistin, will be monitored before Vitamin D supplementation (pre-operatively) and after Vitamin D supplementation (post-operative days 1 and 2). The effect of these changes should be to decrease the incidence of infectious complications. We expect to observe Vitamin D levels increase to normal, and cathelicidin levels become elevated. We expect to see increased levels of resistin in patients developing infections. This study will provide strong pilot evidence for future NIH funding.

Conditions

Vitamin d Deficiency

Keywords

vitamin d deficiency; cathelicidin antimicrobial peptide; resistin, human; protein, human; 1,25-dihydroxy-16,23-diene vitamin D3; Cholecalciferol; Nutritional Status; length of stay

Outcome Measures

Primary Outcomes (1)

• Change in Vitamin D level as measured as 25-OHD level

  Change in Vitamin D level from Pre-Operatively to Post-Operative Day 1 and Post-Operative Day 2

  Pre-operatively, Post-operative Day 1 and Postoperative Day 2

Secondary Outcomes (3)

• Change in Resistin level in the blood

  Pre-operatively, Post-operative Day 1, Post-operative Day 2

• Change in Cathelicidin level in the blood

  Pre-operatively, Post-operative Day 1, Post-operative Day 2

• Change in Calcium Level in the blood

  Pre-operatively, Post-operative Day 1, Post-operative Day 2

Study Arms (2)

Vitamin D3

EXPERIMENTAL

Vitamin D3 (cholecalciferol) 50,000 IU by mouth daily for each of the five days prior to surgery. Blood draw pre-operatively Blood draw post-operative Day 1 Blood draw post-operative Day 2

Procedure: Blood draw pre-operatively; Procedure: Blood draw post-operative Day 1; Procedure: Blood draw post-operative Day 2

Placebo pill

PLACEBO COMPARATOR

Placebo pill by mouth daily for each of the five days prior to surgery. Blood draw pre-operatively Blood draw post-operative Day 1 Blood draw post-operative Day 2

Procedure: Blood draw pre-operatively; Procedure: Blood draw post-operative Day 1; Procedure: Blood draw post-operative Day 2

Interventions

Blood draw pre-operatively PROCEDURE

Pre-Operative blood draw of approximately 32ml will check the following: Vitamin D (25-OHD), Calcium, Cathelicidin and Resistin levels in the blood.

Also known as: Venipuncture

Placebo pill; Vitamin D3

Blood draw post-operative Day 1 PROCEDURE

Blood draw of approximately 32ml to check the following: Vitamin D (25-OHD), Calcium, Cathelicidin and Resistin levels in the blood.

Also known as: Venipuncture

Placebo pill; Vitamin D3

Blood draw post-operative Day 2 PROCEDURE

Blood draw of approximately 32ml to check the following: Vitamin D (25-OHD), Calcium, Cathelicidin and Resistin levels in the blood.

Also known as: Venipuncture

Placebo pill; Vitamin D3

Eligibility Criteria

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

You may qualify if:

• English Speaking
• Age 18 years or older
• Patient undergoing major elective surgery with planned open abdominal incisions, and planned hospitalization of two days or longer.

You may not qualify if:

• Pregnant
• Non-English Speaking
• Chronic severe kidney disease (Stage III, IV, V)

Sponsors & Collaborators

• University of Missouri, Kansas City: lead
• Truman Medical Center: collaborator

Study Sites (1)

Truman Medical Center Hospital Hill

Kansas City, Missouri, 64108, United States

Location

Related Publications (13)

• Flynn L, Zimmerman LH, McNorton K, Dolman M, Tyburski J, Baylor A, Wilson R, Dolman H. Effects of vitamin D deficiency in critically ill surgical patients. Am J Surg. 2012 Mar;203(3):379-82; discussion 382. doi: 10.1016/j.amjsurg.2011.09.012. Epub 2011 Dec 28.

  PMID: 22206852 BACKGROUND

• Bacon CJ, Gamble GD, Horne AM, Scott MA, Reid IR. High-dose oral vitamin D3 supplementation in the elderly. Osteoporos Int. 2009 Aug;20(8):1407-15. doi: 10.1007/s00198-008-0814-9. Epub 2008 Dec 20.

  PMID: 19101755 BACKGROUND

• von Restorff C, Bischoff-Ferrari HA, Theiler R. High-dose oral vitamin D3 supplementation in rheumatology patients with severe vitamin D3 deficiency. Bone. 2009 Oct;45(4):747-9. doi: 10.1016/j.bone.2009.06.012. Epub 2009 Jun 17.

  PMID: 19539796 BACKGROUND

• Amrein K, Sourij H, Wagner G, Holl A, Pieber TR, Smolle KH, Stojakovic T, Schnedl C, Dobnig H. Short-term effects of high-dose oral vitamin D3 in critically ill vitamin D deficient patients: a randomized, double-blind, placebo-controlled pilot study. Crit Care. 2011;15(2):R104. doi: 10.1186/cc10120. Epub 2011 Mar 28.

  PMID: 21443793 BACKGROUND

• Serrone R, Loveless B, Frankel E, Ross V, Geehan D, Van Way, CW III. vitamin D Deficiency in Patients Admitted to a Midwestern Urban Hospital. Poster presentation at Clinical Nutrition Week, American Society of Parenteral and Enteral Nutrition, Phoenix, AZ, 2013

  BACKGROUND

• Braun AB, Litonjua AA, Moromizato T, Gibbons FK, Giovannucci E, Christopher KB. Association of low serum 25-hydroxyvitamin D levels and acute kidney injury in the critically ill. Crit Care Med. 2012 Dec;40(12):3170-9. doi: 10.1097/CCM.0b013e318260c928.

  PMID: 22975885 BACKGROUND

• Schwalfenberg GK. A review of the critical role of vitamin D in the functioning of the immune system and the clinical implications of vitamin D deficiency. Mol Nutr Food Res. 2011 Jan;55(1):96-108. doi: 10.1002/mnfr.201000174. Epub 2010 Sep 7.

  PMID: 20824663 BACKGROUND

• Vieth R. Vitamin D supplementation, 25-hydroxyvitamin D concentrations, and safety. Am J Clin Nutr. 1999 May;69(5):842-56. doi: 10.1093/ajcn/69.5.842.

  PMID: 10232622 BACKGROUND

• Ilahi M, Armas LA, Heaney RP. Pharmacokinetics of a single, large dose of cholecalciferol. Am J Clin Nutr. 2008 Mar;87(3):688-91. doi: 10.1093/ajcn/87.3.688.

  PMID: 18326608 BACKGROUND

• Gombart AF, Bhan I, Borregaard N, Tamez H, Camargo CA Jr, Koeffler HP, Thadhani R. Low plasma level of cathelicidin antimicrobial peptide (hCAP18) predicts increased infectious disease mortality in patients undergoing hemodialysis. Clin Infect Dis. 2009 Feb 15;48(4):418-24. doi: 10.1086/596314.

  PMID: 19133797 BACKGROUND

• White JH. Vitamin D as an inducer of cathelicidin antimicrobial peptide expression: past, present and future. J Steroid Biochem Mol Biol. 2010 Jul;121(1-2):234-8. doi: 10.1016/j.jsbmb.2010.03.034. Epub 2010 Mar 17.

  PMID: 20302931 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

• van der Does AM, Bergman P, Agerberth B, Lindbom L. Induction of the human cathelicidin LL-37 as a novel treatment against bacterial infections. J Leukoc Biol. 2012 Oct;92(4):735-42. doi: 10.1189/jlb.0412178. Epub 2012 Jun 13.

  PMID: 22701042 BACKGROUND

MeSH Terms

Conditions

Vitamin D Deficiency; Muscle Cramp

Interventions

Phlebotomy

Condition Hierarchy (Ancestors)

Avitaminosis; Deficiency Diseases; Malnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Blood Specimen Collection; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Therapeutics; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Charles Van Way III, M.D.

  Truman Medical Center and University of Missouri Kansas City

  STUDY DIRECTOR

• Dustin Neel, MD

  Truman Medical Center and University of Missouri Kansas City

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Co-Principal Investigator

Study Record Dates

• First Submitted: April 9, 2014
• First Posted: May 14, 2014
• Study Start: February 1, 2016
• Primary Completion: May 1, 2016
• Study Completion: May 1, 2016
• Last Updated: June 16, 2017

Record last verified: 2017-06

Locations

US (1)