High Dose Preoperative Cholecalciferol Supplementation and Perioperative Vitamin D Status

Hypovitaminosis D Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01689779
• Other study ID #: 2012P001852
• Status: Completed
• Phase: Phase 3
• First received: September 4, 2012
• Last updated: August 29, 2017
• Start date: January 2013
• Est. completion date: May 2015

Study information

• Verified date: August 2017
• Source: Massachusetts General Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: May 2015
• Est. primary completion date: May 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Avitaminosis
• Hypovitaminosis D
• Rickets
• Vitamin D Deficiency

Intervention

Drug:
• 100,000 IU cholecalciferol
active drug
• Placebo
comparator drug

Locations

Country	Name	City	State
United States	Massachusetts General Hospital	Boston	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Massachusetts General Hospital	Bio-Tech Pharmacal, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	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
Primary	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
Primary	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	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
Secondary	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