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

Completed

• Conditions: Cognitive Decline
• Interventions: Drug: 540,000 IU vitamin D3; Drug: Placebo

• Registration Number: NCT03733418
• Lead Sponsor: Vanderbilt University Medical Center

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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2018-10-30
• Study Start: 2018-11-01
• Study First Submitted QC: 2018-11-06
• Study First Posted: 2018-11-07
• Primary Completion: 2019-10-02
• Study Completion: 2020-02-21
• Results First Submitted: 2022-02-23
• Status Verified: 2024-08
• Results First Submitted QC: 2024-08-01
• Last Update Submitted: 2024-08-01
• Results First Posted: 2024-10-21
• Last Update Posted: 2024-10-21

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 95

Inclusion Criteria

• Patients enrolled in the VIOLET parent study

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Exclusion Criteria

• Deaf or blind
• Non-English speaking

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Intervention	540,000 IU vitamin D3	Patients who received high dose D3 and completed the neuropsychological evaluations at 12 (+/-4) months after randomization.
Placebo	Placebo	Patients who received placebo and completed the neuropsychological evaluations at 12 (+/-4) months after randomization.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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 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.
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 (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 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).

Trial Locations

Locations (7)

University of Colorado Hospital; 🇺🇸 Aurora, Colorado, United States

Brigham and Women's Hospital; 🇺🇸 Boston, Massachusetts, United States

Beth Israel Deaconess Medical Center; 🇺🇸 Boston, Massachusetts, United States

Oregon Health and Science University Hospital; 🇺🇸 Portland, Oregon, United States

Intermountain Medical Center; 🇺🇸 Murray, Utah, United States

Vanderbilt University Medical Center; 🇺🇸 Nashville, Tennessee, United States

Montefiore Medical Center; 🇺🇸 New York, New York, United States