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

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

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.

Study Overview

• Status: Completed
• Conditions: Cognitive Decline
• Intervention / Treatment: Drug: 540,000 IU vitamin D3; Drug: Placebo

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.

• Study Type: Observational
• Enrollment (Actual): 95

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Hospital
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
  • New York
    • New York, New York, United States, 10467
      • Montefiore Medical Center
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science University Hospital
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
  • Utah
    • Murray, Utah, United States, 84107
      • Intermountain Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

584 patients enrolled in VIOLET.

Description

Inclusion Criteria:

• Patients enrolled in the VIOLET parent study

Exclusion Criteria:

• Deaf or blind
• Non-English speaking

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Intervention; Patients who received high dose D3 and completed the neuropsychological evaluations at 12 (+/-4) months after randomization.	Drug: 540,000 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.; Other Names: Cholecalciferol
Placebo; Patients who received placebo and completed the neuropsychological evaluations at 12 (+/-4) months after randomization.	Drug: Placebo; Placebo that matched the vitamin D3 color was provided.

What is the study measuring?

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. Scores range from 0 to 160 with 100 representing the population average. Higher score represents better cognition.	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 score. Scores range from 1 to 18; 10 is considered normal, and higher values indicate better executive function.	12 (+/- 4) months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	12 (+/- 4) months
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.	12 (+/- 4) months
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.	12 (+/- 4) months
Nursing Home Residence at 12-months	Patient resides in a nursing home.	12 (+/- 4) months
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.	12 (+/- 4) months
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.	12 (+/- 4) months
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.	12 (+/- 4) months
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.	12 (+/- 4) months
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.	12 (+/- 4) months
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).	12 months (+/- 4 months)

Collaborators and Investigators

• Sponsor: Vanderbilt University Medical Center
• Collaborators: University of Colorado, Denver; Beth Israel Deaconess Medical Center; Montefiore Medical Center; Brigham and Women's Hospital; Oregon Health and Science University; Intermountain Medical Center
• Investigators: Principal Investigator: Jin H. Han, MD, Vanderbilt University Medical Center

Publications and helpful links

General Publications

• Han JH, Ginde AA, Brown SM, Baughman A, Collar EM, Ely EW, Gong MN, Hope AA, Hou PC, Hough CL, Iwashyna TJ, Jackson JC, Khan A, Orun OM, Patel MB, Raman R, Rice TW, Ringwood N, Semler MW, Shapiro NI, Talmor DS, Self WH; Vitamin D to Improve Outcomes by Leveraging Early Treatment Network Investigators. Effect of Early High-Dose Vitamin D3 Repletion on Cognitive Outcomes in Critically Ill Adults. Chest. 2021 Sep;160(3):909-918. doi: 10.1016/j.chest.2021.03.046. Epub 2021 Apr 2.

Helpful Links

• Pubmed link to manuscript

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2018
• Primary Completion (Actual): October 2, 2019
• Study Completion (Actual): February 21, 2020

Study Registration Dates

• First Submitted: October 30, 2018
• First Submitted That Met QC Criteria: November 6, 2018
• First Posted (Actual): November 7, 2018

Study Record Updates

• Last Update Posted (Actual): October 21, 2024
• Last Update Submitted That Met QC Criteria: August 1, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: critical care; dementia; cognitive decline; vitamin D
• Additional Relevant MeSH Terms: Mental Disorders; Neurocognitive Disorders; Cognition Disorders; Cognitive Dysfunction; Physiological Effects of Drugs; Micronutrients; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Cholecalciferol
• Other Study ID Numbers: 181553

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

This data sharing plan is only pertinent to data collected specifically for VIOLET-BUD. Because VIOLET-BUD is an ancillary study to a Prevention and Early Treatment of Acute Lung Injury (PETAL) network study, the same data sharing plan will be instituted as the PETAL Clinical Coordinating Center. Limited access data sets will be prepared and provided to the NHLBI in accordance with National, Heart, Lung and Blood Institute (NHLBI) policies on data sharing: http://www.nhlbi.nih.gov/research/funding/human-subjects/set-preparation-guidelines.

VIOLET-BUD data will be made available on the Biologic Specimen and Data Repository Information Coordinating Center (BioLINCC). In addition to the data, documentation such as data collection forms, study procedures and protocols, data dictionaries and algorithms for calculated data elements and descriptions of all variable recoding performed will also be provided.

• IPD Sharing Time Frame: Data will be available after the publication of the primary manuscript.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No