Vitamin D to Improve Outcomes by Leveraging Early Treatment: Long-term Brain Outcomes in Vitamin D Deficient Patients

Study Overview
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Brief Summary
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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
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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.

Official Title
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Vitamin D to Improve Outcomes by Leveraging Early Treatment: Long-term Brain Outcomes in Vitamin D Deficient Patients (VIOLET-BUD)

Conditions
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Cognitive Decline

Intervention / Treatment
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* Drug: 540,000 IU vitamin D3
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients enrolled in the VIOLET parent study Exclusion Criteria: Deaf or blind Non-English speaking

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| VIOLET participants<br>Neuropsychological evaluations will be conducted 12 (+/-4) months after randomization among a subset of 140 survivors enrolled in the VIOLET parent study at 7 (out of 42) PETAL sites. | Drug: 540,000 IU vitamin D3<br>* 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.<br>* Other names: Cholecalciferol;Drug: Placebo<br>* Placebo was administered by the VIOLET parent study. A single, liquid enteral dose of placebo was administered.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 12 (+/- 4) months | 
| 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 | 12 (+/- 4) months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 12-month functional status as measured by the Katz Activities of Daily Living (ADL) and Lawton Instrumental Activities of Daily Living (IADL) scales. | The Katz ADL quantifies basic ADLs such as bathing, dressing, toileting, transferring, continence, and feeding. The Lawton IADL quantifies instrumental ADLs such using the telephone, shopping, food preparation, housekeeping, laundry, transportation, medication management, and finances. For the analysis, the Katz ADL and Lawton IADL scales will be summed to provide a functional status score. | 12 (+/- 4) months | 
| 12-month employment as measured by the Outcomes After Critical Illness and Surgery (OACIS) Employment Survey. | The OACIS employment survey will characterize the patient's baseline and current (12 month) employment status. | 12 (+/- 4) months | 
| 12-month death | The patient's death status and time of death will be established during phone contact or medical record review. | 12 (+/- 4) months | 
| 12-month place of residence | 12-month residence status (e.g, home, assisted living, nursing home, etc.,) will be collected during phone contact or medical record review. | 12 (+/- 4) months | 
| 12-month immediate memory | Immediate memory is 1 of the 5 cognitive domains tested in the RBANS. | 12 (+/- 4) months | 
| 12-month visuospatial ability | Visuospatial is 1 of the 5 cognitive domains tested in the RBANS. | 12 (+/- 4) months | 
| 12-month language | Language is 1 of the 5 cognitive domains tested in the RBANS. | 12 (+/- 4) months | 
| 12-month attention | Attention is 1 of the 5 cognitive domains tested in the RBANS. | 12 (+/- 4) months | 
| 12-month delayed memory | Delayed memory is 1 of the 5 cognitive domains tested in the RBANS. | 12 (+/- 4) months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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vitamin D, cognitive decline, dementia, critical care