Hypovitaminosis D
Conditions
Keywords
vitamin D, surgery, acute stress
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.
Interventions
DRUG100,000 IU cholecalciferol
active drug
DRUGPlacebo
comparator drug
Sponsors
Bio-Tech Pharmacal, Inc.
Massachusetts General Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Percent (%) Change in Pre-surgical 25(OH)D 2 Weeks After Surgery | Patients will be followed between the day of surgery and an average duration of 14 days 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. |
| Percent (%) Change in Pre-surgical LL-37 2 Weeks After Surgery | Patients will be followed between the day of surgery and an average duration of 14 days 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cholecalciferol 40 patients will receive 100,000 IU cholecalciferol orally 3-7 days before surgery.
100, 000 IU cholecalciferol | 28 |
| Sugar Pill 40 patients will receive a sugar pill orally 3-7 days before surgery.
Placebo: sugar pill | 32 |
| Total | 60 |
Baseline characteristics
| Characteristic | Cholecalciferol | Sugar Pill | Total |
|---|---|---|---|
| Age, Continuous | 56 years STANDARD_DEVIATION 13 | 61 years STANDARD_DEVIATION 13 | 57 years STANDARD_DEVIATION 13 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 2 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 25 Participants | 28 Participants | 53 Participants |
| Sex: Female, Male Female | 14 Participants | 20 Participants | 34 Participants |
| Sex: Female, Male Male | 14 Participants | 12 Participants | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 28 | 1 / 32 |
| other Total, other adverse events | 0 / 28 | 0 / 32 |
| serious Total, serious adverse events | 0 / 28 | 0 / 32 |
Outcome results
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
Time frame: Patients will be followed between the initial preoperative evaluation day and an average duration of 5 days
Population: Data are presented as percent change in levels between baseline assessment and day of surgery
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cholecalciferol | Percent (%) Change in 25(OH)D 5 Days Following Supplementation With 100,000 IU Cholecalciferol | 8 percent change in 25(OH)D | Standard Deviation 6 |
| Sugar Pill | Percent (%) Change in 25(OH)D 5 Days Following Supplementation With 100,000 IU Cholecalciferol | -2 percent change in 25(OH)D | Standard Deviation 4 |
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
Time frame: Patients will be followed between the initial preoperative evaluation day and an average duration of 5 days
Population: Data are presented as percent change in levels between baseline assessment and day of surgery
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cholecalciferol | Percent (%) Change in LL-37 5 Days Following Supplementation With 100,000 IU Cholecalciferol | -10 percent change in LL-37 | Standard Deviation 17 |
| Sugar Pill | Percent (%) Change in LL-37 5 Days Following Supplementation With 100,000 IU Cholecalciferol | -5 percent change in LL-37 | Standard Deviation 12 |
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.
Time frame: Patients will be followed between the day of surgery and 1 day after surgery
Population: Data are presented as percent change in levels between baseline assessment and day after surgery
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cholecalciferol | Percent (%) Change in Pre-surgical 25(OH)D Within 24 Hours of Surgery | -5 Percent change in 25(OH)D | Standard Deviation 6 |
| Sugar Pill | Percent (%) Change in Pre-surgical 25(OH)D Within 24 Hours of Surgery | -4 Percent change in 25(OH)D | Standard Deviation 4 |
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.
Time frame: Patients will be followed between the day of surgery and 1 day after surgery
Population: Data are presented as percent change in levels between baseline assessment and day after surgery
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cholecalciferol | Percent (%) Change in Pre-surgical LL-37 Within 24 Hours of Surgery | -3 Percent change in LL-37 | Standard Deviation 24 |
| Sugar Pill | Percent (%) Change in Pre-surgical LL-37 Within 24 Hours of Surgery | -5 Percent change in LL-37 | Standard Deviation 31 |
Other Pre-specified
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.
Time frame: Patients will be followed between the day of surgery and an average duration of 14 days after surgery
Population: Data are presented as percent change in levels between baseline assessment and 2 weeks after surgery
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cholecalciferol | Percent (%) Change in Pre-surgical 25(OH)D 2 Weeks After Surgery | 3 Percent change in 25(OH)D | Standard Deviation 7 |
| Sugar Pill | Percent (%) Change in Pre-surgical 25(OH)D 2 Weeks After Surgery | 1 Percent change in 25(OH)D | Standard Deviation 11 |
Other Pre-specified
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.
Time frame: Patients will be followed between the day of surgery and an average duration of 14 days after surgery
Population: Data are presented as percent change in levels between baseline assessment and 2 weeks after surgery
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cholecalciferol | Percent (%) Change in Pre-surgical LL-37 2 Weeks After Surgery | 16 Percent change in LL-37 | Standard Deviation 27 |
| Sugar Pill | Percent (%) Change in Pre-surgical LL-37 2 Weeks After Surgery | 2 Percent change in LL-37 | Standard Deviation 37 |