Cognitive Decline
Conditions
Keywords
vitamin D, cognitive decline, dementia, critical care
Brief summary
This ancillary study will determine if early administration of a single high-dose (540,000 IU) oral vitamin D3 (cholecalciferol) treatment improves 12-month global cognition and executive function as determined by comprehensive neuropsychological testing in 140 critically ill patients with Vitamin D deficiency at enrollment.
Detailed description
VIOLET-BUD is an ancillary study to a parent double-blinded, placebo-controlled randomized control trial (RCT) evaluating how a single, high-dose (540,000 IU) oral Vitamin D3 treatment affects 90-day mortality in patients who are at high risk for ARDS and have Vitamin D deficiency (plasma 25-hydroxyvitamin D \< 20 ng/ml) at enrollment. The parent RCT (Vitamin D to Improve Outcomes by Leveraging Early Treatment \[VIOLET\], NCT03096314) is part of the Clinical Trials Network for the Prevention and Early Treatment of Acute Lung Injury (PETAL) sponsored by the NHLBI. The VIOLET trial completed enrollment in July 2018 with 1,360 randomized to either high dose, enteral Vitamin D3 or placebo. This ancillary study will provide additional funding to perform comprehensive neuropsychological (cognitive) evaluations, which were not part of the parent trial. These neuropsychological evaluations will be conducted 12 (+/- 4) months after randomization among a subset of 140 survivors enrolled in VIOLET. This ancillary study will conducted in 7 (out of 42) sites.
Interventions
DRUG540,000 IU vitamin D3
This intervention was administered as part of VIOLET parent study. A single dose of 540,000 IU vitamin D3 was administered within 2 hours of randomization time.
DRUGPlacebo
Placebo that matched the vitamin D3 color was provided.
Sponsors
Beth Israel Deaconess Medical Center
Brigham and Women's Hospital
University of Colorado, Denver
Montefiore Medical Center
Intermountain Medical Center
Oregon Health and Science University
Vanderbilt University Medical Center
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients enrolled in the VIOLET parent study
Exclusion criteria
* Deaf or blind * Non-English speaking
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 12-month Cognition as Measured by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) | 12 (+/- 4) months | The RBANS is a comprehensive neuropsychological battery for the evaluation of global cognition and has been validated in subjects with mild cognitive impairment, moderate to severe traumatic brain injuries, vascular dementias, and Alzheimer's disease. It specifically tests for for immediate and delayed memory, attention, visuospatial construction, and language. Scores range from 0 to 160 with 100 representing the population average. Higher score represents better cognition. |
| 12-month Executive Function as Measured by the Components of the Delis-Kaplan Executive Function System (D-KEFS) Subscales. | 12 (+/- 4) months | The D-KEF's Proverbs, Number-Letter Switching, and Verbal Fluency Category Switching subscales will measure conceptual flexibility, inhibition, and monitoring, respecitvely, which encompasses the majority of executive function. The average of the three subscales will provide an executive function composite score. Scores range from 1 to 18; 10 is considered normal, and higher values indicate better executive function. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| All-cause Mortality | 12 (+/- 4) months | Patients were contacted and consented at the same time as the 12-month outcome assessments. Therefore, no patients who were enrolled in VIOLET-BUD died. |
| Nursing Home Residence at 12-months | 12 (+/- 4) months | Patient resides in a nursing home. |
| 12-month Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Immediate Memory Domain | 12 (+/- 4) months | Immediate memory is 1 of the 5 cognitive domains tested in the RBANS. Scores range from 40 to 160, with higher scores representing better immediate memory. A score of 100 represents the population average. The standard deviation for the population is 15. |
| 12-month Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Visuospatial Construction Domain | 12 (+/- 4) months | Visuospatial construction is 1 of the 5 cognitive domains tested in the RBANS. Scores range from 40 to 160, with higher scores representing better visuospatial construction. A score of 100 represents the population average. The standard deviation for the population is 15. |
| 12-month Functional Status as Measured by Katz Activities of Daily Living (ADL) Scale. | 12 (+/- 4) months | The Katz ADL quantifies basic ADLs such as bathing, dressing, toileting, transferring, continence, and feeding. Scores range from 0 (completely dependent) to 6 (completely independent). |
| 12-month Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Attention Domain | 12 (+/- 4) months | Attention is 1 of the 5 cognitive domains tested in the RBANS. Scores range from 40 to 160, with higher scores representing better attention. A score of 100 represents the population average. The standard deviation for the population is 15. |
| 12-month Delayed Memory Domain | 12 (+/- 4) months | Delayed memory is 1 of the 5 cognitive domains tested in the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Scores range from 40 to 160, with higher scores representing better delayed memory. A score of 100 represents the population average. The standard deviation for the population is 15. |
| Functional Status as Measured by the Lawton Instrumental Activities of Daily Living Scale. | 12 months (+/- 4 months) | The Lawton IADL quantifies instrumental ADLs such using the telephone, shopping, food preparation, housekeeping, laundry, transportation, medication management, and finances. This scale ranges from 0 (completely dependent) to 8 (completely independent). |
| 12-month (Repeatable Battery for the Assessment of Neuropsychological Status) RBANS Language Domain | 12 (+/- 4) months | Language is 1 of the 5 cognitive domains tested in the RBANS.Scores range from 40 to 160, with higher scores representing better language. A score of 100 represents the population average. The standard deviation for the population is 15. |
| 12-month Loss of Employment | 12 (+/- 4) months | Loss of employmentwas used using the Outcomes After Critical Illness and Surgery (OACIS) Employment Survey and characterizes the patient's baseline and current (12-month) employment status. Patients were defined as having a loss of employment if they went from full to partial or no employment or partial to no employment at 12 months. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Vitamin D3 Participants randomized to the vitamin D3 group received a single enteral (oral or enteral tube) dose of 540,000 IU vitamin D3 (cholecalciferol). | 47 |
| Placebo Patients randomized to the control group received a placebo solution matched in appearance to the vitamin D3 solution. | 48 |
| Total | 95 |
Baseline characteristics
| Characteristic | Placebo | Vitamin D3 | Total |
|---|---|---|---|
| Age, Continuous | 46.0 years | 56 years | 53 years |
| Barona Index | 109.0 units on a scale | 107.7 units on a scale | 108.4 units on a scale |
| Charlson Comorbidity Index | 2 units on a scale | 3 units on a scale | 2 units on a scale |
| Dementia | 4 Participants | 4 Participants | 8 Participants |
| Education, y | 14 years | 14 years | 14 years |
| Facility residence before hospitalization Home (independently) | 39 Participants | 39 Participants | 78 Participants |
| Facility residence before hospitalization Home (with help) | 7 Participants | 5 Participants | 12 Participants |
| Facility residence before hospitalization Home (with professional help) | 0 Participants | 2 Participants | 2 Participants |
| Facility residence before hospitalization Nursing facility | 2 Participants | 1 Participants | 3 Participants |
| Infection (Sepsis + Pneumonia) | 30 Participants | 30 Participants | 60 Participants |
| Race/Ethnicity, Customized Race American Indian or Alaskan Native | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Race Asian | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Race Black or African American | 8 Participants | 4 Participants | 12 Participants |
| Race/Ethnicity, Customized Race Multiple race | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Race Native Hawaiian or other Pacific Islander | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Race Other | 5 Participants | 0 Participants | 5 Participants |
| Race/Ethnicity, Customized Race White | 31 Participants | 40 Participants | 71 Participants |
| Sex: Female, Male Female | 25 Participants | 21 Participants | 46 Participants |
| Sex: Female, Male Male | 23 Participants | 26 Participants | 49 Participants |
| SOFA Score | 5 units on a scale | 4 units on a scale | 5 units on a scale |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 47 | 0 / 48 |
| other Total, other adverse events | 0 / 47 | 0 / 48 |
| serious Total, serious adverse events | 0 / 47 | 0 / 48 |
Outcome results
Primary
12-month Cognition as Measured by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)
The RBANS is a comprehensive neuropsychological battery for the evaluation of global cognition and has been validated in subjects with mild cognitive impairment, moderate to severe traumatic brain injuries, vascular dementias, and Alzheimer's disease. It specifically tests for for immediate and delayed memory, attention, visuospatial construction, and language. Scores range from 0 to 160 with 100 representing the population average. Higher score represents better cognition.
Time frame: 12 (+/- 4) months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Vitamin D3 | 12-month Cognition as Measured by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) | 79.6 units on a scale |
| Placebo | 12-month Cognition as Measured by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) | 82.1 units on a scale |
Primary
12-month Executive Function as Measured by the Components of the Delis-Kaplan Executive Function System (D-KEFS) Subscales.
The D-KEF's Proverbs, Number-Letter Switching, and Verbal Fluency Category Switching subscales will measure conceptual flexibility, inhibition, and monitoring, respecitvely, which encompasses the majority of executive function. The average of the three subscales will provide an executive function composite score. Scores range from 1 to 18; 10 is considered normal, and higher values indicate better executive function.
Time frame: 12 (+/- 4) months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Vitamin D3 | 12-month Executive Function as Measured by the Components of the Delis-Kaplan Executive Function System (D-KEFS) Subscales. | 8.1 units on a scale |
| Placebo | 12-month Executive Function as Measured by the Components of the Delis-Kaplan Executive Function System (D-KEFS) Subscales. | 8.7 units on a scale |
Secondary
12-month Delayed Memory Domain
Delayed memory is 1 of the 5 cognitive domains tested in the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Scores range from 40 to 160, with higher scores representing better delayed memory. A score of 100 represents the population average. The standard deviation for the population is 15.
Time frame: 12 (+/- 4) months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Vitamin D3 | 12-month Delayed Memory Domain | 85.1 score on a scale |
| Placebo | 12-month Delayed Memory Domain | 84.6 score on a scale |
Secondary
12-month Functional Status as Measured by Katz Activities of Daily Living (ADL) Scale.
The Katz ADL quantifies basic ADLs such as bathing, dressing, toileting, transferring, continence, and feeding. Scores range from 0 (completely dependent) to 6 (completely independent).
Time frame: 12 (+/- 4) months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Vitamin D3 | 12-month Functional Status as Measured by Katz Activities of Daily Living (ADL) Scale. | 6.0 score on a scale |
| Placebo | 12-month Functional Status as Measured by Katz Activities of Daily Living (ADL) Scale. | 6.0 score on a scale |
Secondary
12-month Loss of Employment
Loss of employmentwas used using the Outcomes After Critical Illness and Surgery (OACIS) Employment Survey and characterizes the patient's baseline and current (12-month) employment status. Patients were defined as having a loss of employment if they went from full to partial or no employment or partial to no employment at 12 months.
Time frame: 12 (+/- 4) months
Population: Patients who were partially or fully employed prior to randomization.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Vitamin D3 | 12-month Loss of Employment | 7 Participants |
| Placebo | 12-month Loss of Employment | 10 Participants |
Secondary
12-month Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Attention Domain
Attention is 1 of the 5 cognitive domains tested in the RBANS. Scores range from 40 to 160, with higher scores representing better attention. A score of 100 represents the population average. The standard deviation for the population is 15.
Time frame: 12 (+/- 4) months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Vitamin D3 | 12-month Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Attention Domain | 87.9 score on a scale |
| Placebo | 12-month Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Attention Domain | 90.1 score on a scale |
Secondary
12-month Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Immediate Memory Domain
Immediate memory is 1 of the 5 cognitive domains tested in the RBANS. Scores range from 40 to 160, with higher scores representing better immediate memory. A score of 100 represents the population average. The standard deviation for the population is 15.
Time frame: 12 (+/- 4) months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Vitamin D3 | 12-month Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Immediate Memory Domain | 84.1 score on a scale |
| Placebo | 12-month Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Immediate Memory Domain | 87.6 score on a scale |
Secondary
12-month (Repeatable Battery for the Assessment of Neuropsychological Status) RBANS Language Domain
Language is 1 of the 5 cognitive domains tested in the RBANS.Scores range from 40 to 160, with higher scores representing better language. A score of 100 represents the population average. The standard deviation for the population is 15.
Time frame: 12 (+/- 4) months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Vitamin D3 | 12-month (Repeatable Battery for the Assessment of Neuropsychological Status) RBANS Language Domain | 95.7 score on a scale |
| Placebo | 12-month (Repeatable Battery for the Assessment of Neuropsychological Status) RBANS Language Domain | 95.6 score on a scale |
Secondary
12-month Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Visuospatial Construction Domain
Visuospatial construction is 1 of the 5 cognitive domains tested in the RBANS. Scores range from 40 to 160, with higher scores representing better visuospatial construction. A score of 100 represents the population average. The standard deviation for the population is 15.
Time frame: 12 (+/- 4) months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Vitamin D3 | 12-month Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Visuospatial Construction Domain | 70.7 score on a scale |
| Placebo | 12-month Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Visuospatial Construction Domain | 68.7 score on a scale |
Secondary
All-cause Mortality
Patients were contacted and consented at the same time as the 12-month outcome assessments. Therefore, no patients who were enrolled in VIOLET-BUD died.
Time frame: 12 (+/- 4) months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Vitamin D3 | All-cause Mortality | 0 Participants |
| Placebo | All-cause Mortality | 0 Participants |
Secondary
Functional Status as Measured by the Lawton Instrumental Activities of Daily Living Scale.
The Lawton IADL quantifies instrumental ADLs such using the telephone, shopping, food preparation, housekeeping, laundry, transportation, medication management, and finances. This scale ranges from 0 (completely dependent) to 8 (completely independent).
Time frame: 12 months (+/- 4 months)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Vitamin D3 | Functional Status as Measured by the Lawton Instrumental Activities of Daily Living Scale. | 8.0 score on a scale |
| Placebo | Functional Status as Measured by the Lawton Instrumental Activities of Daily Living Scale. | 8.0 score on a scale |
Secondary
Nursing Home Residence at 12-months
Patient resides in a nursing home.
Time frame: 12 (+/- 4) months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Vitamin D3 | Nursing Home Residence at 12-months | 1 Participants |
| Placebo | Nursing Home Residence at 12-months | 1 Participants |