Vitamin D to ENhance TraUma REcovery

NCT ID: NCT05458024

Last Updated: 2025-03-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 71 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-01-24
• Study Completion Date: 2024-05-01

Brief Summary

The main objective of this study is to determine whether the administration of a single dose of Vitamin D in the Emergency Department following a motor vehicle collision can improve musculoskeletal pain severity as well as reduce musculoskeletal pain outcome disparity between Blacks and White following a motor vehicle collision. This randomized controlled trial is a pilot study to determine feasibility and potential efficacy (response to study drug, ability to reduce racial disparity in pain outcomes). This data can be used to adequately power a larger randomized controlled trial to fully assess efficacy.

Detailed Description

Motor vehicle collisions (MVCs) are one of the most common traumatic stress exposures in the US, and the most common for which individuals seek emergency department (ED) care. More than 1 million Black Americans (Blacks) come to the ED after MVC each year, and >90% of such ED MVC patients are discharged home with a diagnosis of acute musculoskeletal pain (MSP)/strain only. More than 80% of these individuals report acute moderate or severe (mod/sev) MSP in the ED, and >50% of those with acute mod/sev MSP transition to chronic MSP. MVCs, as well as pain after MVC, disproportionately affect Blacks vs. Whites. For example, in previous cohort studies 67% of Blacks had mod/sev MSP six months after MVC, vs. only 40% of Whites. Interventions are urgently needed that prevent chronic MSP and reduce these MSP outcome disparities.

One safe, inexpensive, widely available, and well-tolerated intervention, with exciting potential to achieve these goals, is Vitamin D (Vitamin D). The dose of Ergocalciferol that the investigators propose, 300,000 IU, has been shown to effectively raise Vitamin D concentration by ~9 ng/ml, and to raise serum 25 hydroxyvitamin D concentration above 30 ng/ml (Vitamin D sufficient levels) for over 3 months5. The ability of this single-dose protocol to raise Vitamin D will be a primary feasibility endpoint of this pilot study.

Importantly, this dose is extremely well-tolerated: in previous trials, reports of side effects/adverse events is rare,6 many studies administering single, high-dose regimens report no side effects7-9, and the most common side effects have been mild GI complaints (e.g. nausea).6 Vitamin D administration has also been demonstrated to be safe, even among individuals who are already Vitamin D sufficient. 10-12

Chronic pain is associated with reduced mental and physical health and interferes with essential activities of daily life. Currently there are limited treatment options to address chronic pain once it has become established and the overarching aim of this clinical trial is to prevent chronic pain development, therefore there is a critical unmet need of safe, non-addictive, non-invasive preventative treatment options that can be administered to MVC survivors in the aftermath of an injury. This study has the potential to benefit participants and future MVC survivors and improve pain and general health outcomes. The risks of taking Vitamin D are small. Side effects from Vitamin D are rare, however, it is possible that over supplementation of Vitamin D may be associated with headache, loss of appetite, dry mouth, metallic taste, and nausea/vomiting.

Primary Objective:

1. Assess the feasibility of the Randomized Controlled Trial (RCT) protocol by (a) calculating recruitment rate and participant retention, and (b) measuring the ability of Vitamin D administration to generate sustained increases in whole-blood Vitamin D concentrations (assessed 3 months after MVC).

2. To demonstrate the preliminary efficacy of Vitamin D administration per protocol on decreasing overall MSP severity during the 3 months following MVC, and reducing MSP outcome disparity between Blacks and Whites following MVC.

Secondary Objectives:

The investigators will assess the effect of race and sex on treatment outcomes in secondary analyses. This will be accomplished using two analytic strategies. First, a sex X treatment interaction term (secondary analyses) will be entered into the statistical models to assess pain reduction in response to treatment. Second, a stratified analysis will be performed which will examine the influence of both sex and race on treatment effect on primary and secondary outcomes. Further, Secondary stratified analyses evaluate the influence of initial vitamin D level on treatment response. In addition, exploratory analyses on the relationship of vitamin D outcome and trajectory of pain as well as restricting analyses to participants with vitamin D deficiency at baseline will be performed. Secondary analyses will examine treatment effects adjusting for any baseline differences in psychosocial factors between treatment arms.

Long-Term Aims Beyond the Present Proposal:

To use data collected to design and adequately power a larger-scale RCT assessing the efficacy of Vitamin D treatment in decreasing chronic pain in high-risk patients presenting for treatment in the aftermath of MVC and to reduce racial disparity in pain outcomes following MVC.

Described the sequence of events in recruiting 90 patients in a multi-center randomized controlled trial. To assess a key primary outcome, 50% white and 50% black MVC will be enrolled into the study. Each participant will be screened in based on a point of care Vitamin D test. This will be performed at the time of screening. Individuals with a Vitamin D level <100 ng/ml will be enrolled. Patients will be randomized 1:1 to receive a single dose of 300,000 IU of ergocalciferol versus placebo and followed for 3 months. At 3 months, patients will send a blood sample easily collected at home on a blood spot card to assess Vitamin D level 3 months following injury which is a key feasibility primary outcome.

Patients presenting to the ED within 24 hours of MVC (n=90, 45 non-Hispanic Black, and 45 non-Hispanic White) will receive a single dose of study drug prior to ED discharge (1:1 allocation 300,000 IU ergocalciferol or placebo). Prior to study drug administration, a baseline assessment will be performed (see below), and a fingerstick blood sample will be obtained to evaluate 25-hydroxyvitamin D level. Telephone follow-ups assessing primary and secondary outcomes and potential adverse events will be performed 3 weeks, 6 weeks, and 3 months after ED enrollment by study Research Assistants using web-based REDCap™ software. At 3 months, participants will also perform fingerstick blood collection at home and mail to the study team to enable assessment of 3 month 25-hydroxyvitamin D concentration by treatment group.

Conditions

Musculoskeletal Pain

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Ergocalciferol (Vitamin D2)

300,000 international units (IUs) of Ergocalciferol in 6 50,000 IU capsules. These will be given in a single dose prior to discharge from the Emergency Department.

Group Type: ACTIVE_COMPARATOR

Vitamin D 2

Intervention Type: DRUG

300,000 international units (IUs) of Ergocalciferol in 6 50,000 IU capsules.

Ergocalciferol placebo

Inert substance will be administered in 6 capsules indistinguishable from the 50,000 IU Ergocalciferol capsules administered in the active treatment arm.

Group Type: PLACEBO_COMPARATOR

Vitamin D2 Placebo

Intervention Type: DRUG

Inert substance will be administered in 6 capsules indistinguishable from the 50,000 IU

Interventions

Vitamin D 2

300,000 international units (IUs) of Ergocalciferol in 6 50,000 IU capsules.

Intervention Type: DRUG

Vitamin D2 Placebo

Inert substance will be administered in 6 capsules indistinguishable from the 50,000 IU

Intervention Type: DRUG

Other Intervention Names

Ergocalciferol 300,000 IU; Ergocalciferol Placebo

Eligibility Criteria

Inclusion Criteria

• ≥ 18 years and ≤ 65 years of age
• Admitted to ED within 24 hours of motor vehicle collision
• Plan to discharge to home from the emergency department
• Stated willingness to comply with all study procedures and availability for the duration of the study (with the exception of the blood draw sample collected in the ED, which is optional)
• Has a smartphone with continuous service >1 year
• Able to speak and read English
• Alert and oriented, and capable of engaging in informed consent
• Willing to take on-time dose of study medication (6 capsules of Vitamin D or placebo)
• Non-Hispanic white or non-Hispanic black
• Point of care Vitamin D level <100 ng/ml
• During ED admission pain severity must be at least 4/10 or higher

Exclusion Criteria

• Substantial comorbid injury (e.g., long bone fracture)
• Pregnancy/breastfeeding
• Prisoner status
• Chronic daily opioid use prior to MVC (>20 mg oral daily morphine equivalents)
• Active psychosis, suicidal ideation, or homicidal ideation
• Plans for hospital admission
• Known chronic kidney disease, stage 4 or higher (GFR≤29)
• Intubated and sedated at time of enrollment
• Inability to provide informed consent (receipt of sedative, hypnotic agent making the patient non-decisional for consent)
• Vitamin D supplements in excess of 800 IU daily
• Any other history or condition that would, in the site investigator's judgement, indicate that the patient would very likely be non-compliant with the study or unsuitable for the study (e.g., might interfere with the study, confound interpretation, or endanger patient)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institute on Minority Health and Health Disparities (NIMHD)

NIH

Sponsor Role: collaborator

University of North Carolina, Chapel Hill

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Samuel McLean

Role: PRINCIPAL_INVESTIGATOR

University of North Carolina, Chapel Hill

Locations

University of Massachusetts Medical School

Worcester, Massachusetts, United States

Washington University School of Medicine

St Louis, Missouri, United States

Cooper University Hospital

Camden, New Jersey, United States

Rhode Island Hospital

Providence, Rhode Island, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

R21MD016467

Identifier Type: NIH

Identifier Source: secondary_id

View Link

21-2589

Identifier Type: -

Identifier Source: org_study_id