High Dose Preoperative Cholecalciferol Supplementation and Perioperative Vitamin D Status

Study Overview
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Brief Summary
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A growing body of evidence suggests that robust postoperative immune function is associated with a lower risk of surgical site infections (SSIs). At the same time, vitamin D is increasingly recognized as a key regulator of the innate and adaptive immune systems. The investigators elected to conduct the current study in patients who will undergo colorectal surgery since these patients are historically at higher risk of developing SSIs and therefore would be ideal for future investigations.

Detailed Description
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While vitamin D insufficiency [25(OH)D <30 ng/mL] is common in the general population, hypovitaminosis D may affect 40-80% of patients in the perioperative setting. Recent evidence also suggests that surgical stress may be associated with a 40% reduction in circulating 25(OH)D levels when compared to preoperative values. Moreover, the derangement in perioperative 25(OH)D levels may be sustained for up to 3 months after surgery. This finding has potential implications regarding modifiable risk factors for surgical site infections (SSIs), which account for nearly 40% of all nosocomial infections. On aggregate, SSIs result in 3.7 million extra hospital days per annum and an added burden of $1.6 billion in annual healthcare costs. A growing body of evidence suggests that robust postoperative immune function is associated with a lower risk of SSIs. At the same time, vitamin D is increasingly recognized as a key regulator of the innate and adaptive immune systems. Yet, optimization of perioperative vitamin D status remains grossly understudied. Although our overarching aim is to study the impact of vitamin D status on SSIs, the focus of the current investigation is to determine whether the administration of a bolus oral dose of cholecalciferol (vitamin D3) in the preoperative setting alters vitamin D status in the perioperative setting (compared to a placebo). The investigators elected to conduct the current study in patients who will undergo colorectal surgery since these patients are historically at higher risk of developing SSIs and therefore would be ideal for future investigations.

Official Title
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Effect of High-dose Cholecalciferol Supplementation on Perioperative Vitamin D Status in Colorectal Surgery Patients

Conditions
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Hypovitaminosis D

Intervention / Treatment
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* Drug: 100,000 IU cholecalciferol
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women; 18 years or older; Scheduled for elective (non-emergent) colorectal surgery; Cleared for anesthesia; and Expected to stay overnight following surgery Exclusion Criteria: Scheduled for a purely laparoscopic procedure; Diagnosis of a terminal illness and/or in hospice care; Inability to sign informed consent; Inability to comply with study protocol; Intending to start vitamin D supplementation within 30 days of surgery; Intending to leave the Boston area during the follow-up period; History of renal stones or hypercalcemia; Medical conditions that can cause hypercalcemia (e.g. metastatic cancer, sarcoidosis, myeloma primary hyperparathyroidism) History of hypercalcemia History of severe anemia (Hematocrit <25%) Medications that affect vitamin D metabolism (e.g. anti-epileptics, tuberculosis medication); and Already enrolled or planning to enroll in a research study that would conflict with full participation in the current study or confound the observation or interpretation of the study findings

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Cholecalciferol<br>A maximum of 40 patients will receive a one-time oral dose of 100,000 IU cholecalciferol 3-7 days before their scheduled elective surgery. | Drug: 100,000 IU cholecalciferol<br>* active drug<br>* Other names: vitamin D3;|
| Placebo Comparator: Placebo<br>A maximum of 40 patients will receive a one-time oral sugar pill 3-7 days before their scheduled elective surgery. | Drug: Placebo<br>* comparator drug<br>* Other names: sugar pill;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent (%) Change in 25(OH)D 5 Days Following Supplementation With 100,000 IU Cholecalciferol | 3-7 days before surgery, patients will receive 100,000 IU of cholecalciferol (vs. placebo) during their pre-op assessment. They will also have their baseline vitamin D status measured during this initial visit. The main study outcome is to determine if 100,000 IU cholecalciferol can be given preoperatively to safely boost vitamin D status. To assess vitamin D status, we will measure: 1) 25(OH)D and 2) LL37 | Patients will be followed between the initial preoperative evaluation day and an average duration of 5 days | 
| Percent (%) Change in LL-37 5 Days Following Supplementation With 100,000 IU Cholecalciferol | 3-7 days before surgery, patients will receive 100,000 IU of cholecalciferol (vs. placebo) during their pre-op assessment. They will also have their baseline vitamin D status measured during this initial visit. The main study outcome is to determine if 100,000 IU cholecalciferol can be given preoperatively to safely boost vitamin D status. To assess vitamin D status, we will measure: 1) 25(OH)D and 2) LL37 | Patients will be followed between the initial preoperative evaluation day and an average duration of 5 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent (%) Change in Pre-surgical 25(OH)D Within 24 Hours of Surgery | The goal is to determine whether pre-operative supplementation with 100,000 IU cholecalciferol (vs. placebo) alters the natural course of short-term changes in vitamin D status following surgery. To assess vitamin D status, we will measure: 1) 25(OH)D and 2) LL37. | Patients will be followed between the day of surgery and 1 day after surgery | 
| Percent (%) Change in Pre-surgical LL-37 Within 24 Hours of Surgery | The goal is to determine whether pre-operative supplementation with 100,000 IU cholecalciferol (vs. placebo) alters the natural course of short-term changes in vitamin D status following surgery. To assess vitamin D status, we will measure: 1) 25(OH)D and 2) LL37. | Patients will be followed between the day of surgery and 1 day after surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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vitamin D, surgery, acute stress