High Dose Preoperative Cholecalciferol Supplementation and Perioperative Vitamin D Status

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

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.

Study Overview

• Status: Completed
• Conditions: Hypovitaminosis D
• Intervention / Treatment: Drug: 100,000 IU cholecalciferol; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital

Participation Criteria

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:

• 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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent (%) Change in Pre-surgical 25(OH)D 2 Weeks After Surgery	The goal is to determine whether pre-operative supplementation with 100,000 IU cholecalciferol (vs. placebo) alters the natural course of changes in vitamin D status within 10-18 days after surgery. To assess vitamin D status, we will measure: 1) 25(OH)D and 2) LL-37.	Patients will be followed between the day of surgery and an average duration of 14 days after surgery
Percent (%) Change in Pre-surgical LL-37 2 Weeks After Surgery	The goal is to determine whether pre-operative supplementation with 100,000 IU cholecalciferol (vs. placebo) alters the natural course of changes in vitamin D status within 10-18 days after surgery. To assess vitamin D status, we will measure: 1) 25(OH)D and 2) LL-37.	Patients will be followed between the day of surgery and an average duration of 14 days after surgery

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Collaborators: Bio-Tech Pharmacal, Inc.
• Investigators: Principal Investigator: Sadeq A Quraishi, MD, MHA, Massachusetts General Hospital

Study record dates

Study Major Dates

• Study Start: January 1, 2013
• Primary Completion (Actual): May 1, 2015
• Study Completion (Actual): May 1, 2015

Study Registration Dates

• First Submitted: September 4, 2012
• First Submitted That Met QC Criteria: September 17, 2012
• First Posted (Estimate): September 21, 2012

Study Record Updates

• Last Update Posted (Actual): September 28, 2017
• Last Update Submitted That Met QC Criteria: August 29, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Keywords: surgery; vitamin D; acute stress
• Additional Relevant MeSH Terms: Metabolic Diseases; Nutrition Disorders; Musculoskeletal Diseases; Deficiency Diseases; Malnutrition; Bone Diseases; Bone Diseases, Metabolic; Calcium Metabolism Disorders; Vitamin D Deficiency; Rickets; Avitaminosis; Physiological Effects of Drugs; Micronutrients; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Cholecalciferol
• Other Study ID Numbers: 2012P001852

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

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