Therapeutic Benefit of Preoperative Supplemental Vitamin D in Patients Undergoing Major Surgical Procedures.
| Status: | Withdrawn |
|---|---|
| Conditions: | Other Indications, Gastrointestinal |
| Therapuetic Areas: | Gastroenterology, Other |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 5/14/2016 |
| Start Date: | February 2016 |
| End Date: | May 2016 |
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.
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.
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.
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.
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)
We found this trial at
1
site
Kansas City, Missouri 64108
Principal Investigator: Dustin Neel, M.D.
Phone: 816-404-1380
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