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

June 14, 2017 updated by: Dustin Neel, University of Missouri, Kansas City
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.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Missouri
      • Kansas City, Missouri, United States, 64108
        • Truman Medical Center Hospital Hill

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Vitamin D3

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
Pre-Operative blood draw of approximately 32ml will check the following: Vitamin D (25-OHD), Calcium, Cathelicidin and Resistin levels in the blood.
Other Names:
  • Venipuncture
Procedure: Blood draw post-operative Day 1
Blood draw of approximately 32ml to check the following: Vitamin D (25-OHD), Calcium, Cathelicidin and Resistin levels in the blood.
Other Names:
  • Venipuncture
Procedure: Blood draw post-operative Day 2
Blood draw of approximately 32ml to check the following: Vitamin D (25-OHD), Calcium, Cathelicidin and Resistin levels in the blood.
Other Names:
  • Venipuncture
Placebo Comparator: Placebo pill
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
Pre-Operative blood draw of approximately 32ml will check the following: Vitamin D (25-OHD), Calcium, Cathelicidin and Resistin levels in the blood.
Other Names:
  • Venipuncture
Procedure: Blood draw post-operative Day 1
Blood draw of approximately 32ml to check the following: Vitamin D (25-OHD), Calcium, Cathelicidin and Resistin levels in the blood.
Other Names:
  • Venipuncture
Procedure: Blood draw post-operative Day 2
Blood draw of approximately 32ml to check the following: Vitamin D (25-OHD), Calcium, Cathelicidin and Resistin levels in the blood.
Other Names:
  • Venipuncture

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Vitamin D level as measured as 25-OHD level
Time Frame: Pre-operatively, Post-operative Day 1 and Postoperative Day 2
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Resistin level in the blood
Time Frame: Pre-operatively, Post-operative Day 1, Post-operative Day 2
Change in Resistin level from Pre-Operatively to Post-Operative Day 1 and Post-Operative Day 2
Pre-operatively, Post-operative Day 1, Post-operative Day 2
Change in Cathelicidin level in the blood
Time Frame: Pre-operatively, Post-operative Day 1, Post-operative Day 2
Change in Cathelicidin level from Pre-Operatively to Post-Operative Day 1 and Post-Operative Day 2
Pre-operatively, Post-operative Day 1, Post-operative Day 2
Change in Calcium Level in the blood
Time Frame: Pre-operatively, Post-operative Day 1, Post-operative Day 2
Change in Calcium level from Pre-Operatively to Post-Operative Day 1 and Post-Operative Day 2
Pre-operatively, Post-operative Day 1, Post-operative Day 2

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Missouri, Kansas City

Collaborators

Truman Medical Center

Investigators

  • Study Director: Charles Van Way III, M.D., Truman Medical Center and University of Missouri Kansas City
  • Principal Investigator: Dustin Neel, MD, Truman Medical Center and University of Missouri Kansas City

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2016

Primary Completion (Actual)

May 1, 2016

Study Completion (Actual)

May 1, 2016

Study Registration Dates

First Submitted

April 9, 2014

First Submitted That Met QC Criteria

May 12, 2014

First Posted (Estimate)

May 14, 2014

Study Record Updates

Last Update Posted (Actual)

June 16, 2017

Last Update Submitted That Met QC Criteria

June 14, 2017

Last Verified

June 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 14-149

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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