High Dose Preoperative Cholecalciferol Supplementation and Perioperative Vitamin D Status

Phase 3

Completed

Conditions: Hypovitaminosis D

Interventions: Drug: 100,000 IU cholecalciferol
Drug: Placebo

Registration Number: NCT01689779

Lead Sponsor: Massachusetts General Hospital

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 60

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cholecalciferol	100,000 IU cholecalciferol	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.
Placebo	Placebo	A maximum of 40 patients will receive a one-time oral sugar pill 3-7 days before their scheduled elective surgery.

Primary Outcome Measures

Name	Time	Method
Percent (%) Change in 25(OH)D 5 Days Following Supplementation With 100,000 IU Cholecalciferol	Patients will be followed between the initial preoperative evaluation day and an average duration of 5 days	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
Percent (%) Change in LL-37 5 Days Following Supplementation With 100,000 IU Cholecalciferol	Patients will be followed between the initial preoperative evaluation day and an average duration of 5 days	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

Secondary Outcome Measures

Name	Time	Method
Percent (%) Change in Pre-surgical LL-37 Within 24 Hours of Surgery	Patients will be followed between the day of surgery and 1 day after 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.
Percent (%) Change in Pre-surgical 25(OH)D Within 24 Hours of Surgery	Patients will be followed between the day of surgery and 1 day after 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.