Clinical trial NCT02138591: Therapeutic Benefit of Preoperative Supplemental Vitamin D in Patients Undergoing Major Surgical Procedures.
Official title: Therapeutic Benefit of Preoperative Supplemental Vitamin D in Patients Undergoing Major Surgical Procedures.
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE3
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
Lead sponsor: University of Missouri, Kansas City
Sponsor class: OTHER
Collaborators: name: Truman Medical Center
First posted: 2014-05-14
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Detailed description: The long term goal in our research is to develop and implement effective, evidence-and mechanism-based interventions to improve outcomes for surgical and trauma patients. Of potential importance, findings from our own recent pilot studies have established that \> 95% of patients seen at Truman Medical Center (TMC) are seriously Vitamin D deficient with plasma levels significantly lower than normal. Our objective in this application, therefore, is to assess the short term therapeutic benefit of high dose Vitamin D in patients admitted to TMC for elective major abdominal surgery. We propose to measure plasma Vitamin D and Calcium levels before supplementation (pre-operatively), and after supplementation (post-operatively), and monitor the biomarker proteins cathelicidin and resistin at the same times. Data on Vitamin D levels will be used to assess direct biochemical effects. Measurement of cathelicidin levels will provide additional information. Since Vitamin D has been shown to induce increased expression of this antimicrobial protein. Monitoring of circulating levels of resistin provides a highly sensitive early measure of infection (unpublished observations). Calcium levels will also be monitored since there is a significant chance that pre-operative calcium levels will be low in some patients, and that supplementation with vitamin D may increase the calcium level.

Measures of secondary clinical outcomes will include length of hospital stay and incidence of post-operation infection. Our central hypothesis is that, relative to patients receiving peri-operative standard of care, patients receiving 250,000 units of Vitamin D pre-operatively will manifest levels of Vitamin D to within the normal range and will have elevated levels of cathelicidin. We further hypothesize that patients receiving Vitamin D will have reduced incidence of infection, which will correlate with lower levels of resistin, and will exhibit trends toward shorter hospital stay. Our proposed specific aims are:

Specific Aim #1: Determine biochemical consequences of Vitamin D supplementation in elective surgery patients We hypothesize that preoperative supplementation with high dose Vitamin D will result in levels of Vitamin D in treated patients within the normal range, corresponding with significant increases in plasma levels of cathelicidin, relative to control patients receiving standard of care.

Specific Aim # 2: Evaluate clinical benefits of Vitamin D supplementation in post-elective surgery patients We postulate that patients given Vitamin D will trend toward lower rates of post-surgery infection, as evidenced by the absence of circulating resistin and decreased detection of pulmonary or wound-site infection, and will have shorter hospital stays relative to patients receiving standard of care.

It is our expectation that, at the completion of this pilot study, we will have provided strong evidence that plasma levels of Vitamin D, as measured by 25-OHD, can be reproducibly raised to normal levels as measured in post-surgery patients and that the administered Vitamin D will have detectable biochemical benefits. We further expect that, while the power of the proposed study will not be sufficient for statistically valid results, there will be trends toward clinical benefits in Vitamin D treated patients. Collectively, these findings would provide strong evidence to support feasibility of an NIH-supported Phase I trial to assess Vitamin D benefits in surgery and/or trauma.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

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

Primary outcomes:
measure: Change in Vitamin D level as measured as 25-OHD level
timeFrame: Pre-operatively, Post-operative Day 1 and Postoperative Day 2
Secondary outcomes:
measure: Change in Resistin level in the blood
timeFrame: Pre-operatively, Post-operative Day 1, Post-operative Day 2
measure: Change in Cathelicidin level in the blood
timeFrame: Pre-operatively, Post-operative Day 1, Post-operative Day 2
measure: Change in Calcium Level in the blood
timeFrame: Pre-operatively, Post-operative Day 1, Post-operative Day 2
Other outcomes:
Locations:
city: Kansas City
country: United States
facility: Truman Medical Center Hospital Hill
state: Missouri
Study officials:
affiliation: Truman Medical Center and University of Missouri Kansas City
name: Charles Van Way III, M.D.
role: STUDY_DIRECTOR
affiliation: Truman Medical Center and University of Missouri Kansas City
name: Dustin Neel, MD
role: PRINCIPAL_INVESTIGATOR
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