Randomized Controlled Trial of Vitamin D to Reduce Racial Disparity in Chronic Pain Following Motor Vehicle Collision
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Enrollment
- 71
- Locations
- 4
- Primary Endpoint
- Chronic Pain Severity
Study Overview
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:
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Prevention
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description
This will be a blinded study. Investigators, participants, and coordinators will be blinded to the treatment assignment. Active and placebo treatments will be indistinguishable.
Eligibility Criteria
- Ages
- 18 Years to 65 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
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)
Arms & Interventions
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.
Intervention: Vitamin D 2 (Drug)
Ergocalciferol placebo
Inert substance will be administered in 6 capsules indistinguishable from the 50,000 IU Ergocalciferol capsules administered in the active treatment arm.
Intervention: Vitamin D2 Placebo (Drug)
Outcomes
Primary Outcomes
Chronic Pain Severity
Time Frame: Over 3 months following MVC
Estimates of efficacy will be obtained via repeated measures analysis of pain severity over the 3 months following injury using mixed effects models. Pain will be assessed using a 0-10 numeric rating scale with 0 indicating no pain and 10 indicating pain as severe as one can imagine. Higher scores represent worse outcome. These values (collected in identical fashion over 3 months following motor vehicle collision) will be entered into a linear mixed model, and overall effect estimates (beta coefficients) among treatment groups will be determined
Percent of Participants Who Are Compliant With Follow-up (Feasibility)
Time Frame: through study completion, 3 months following MVC
The primary objective of this study is to ensure that the investigators are able to make follow-up assessments on a majority of participants. The percent of participants who are compliant with follow-up will be determined 3 months following their motor vehicle collision. Feasibility is defined as \>80% of enrolled participants at 3 months following Motor Vehicle Collision (MVC).
Chronic Pain Race X Treatment Arm Interaction
Time Frame: Over 3 months following MVC
Estimates of interaction between race and treatment assignment will be obtained via repeated measures analysis of pain severity over the 3 months following injury using mixed effects models. Pain will be assessed using a 0-10 numeric rating scale with 0 indicating no pain and 10 indicating pain as severe as one can imagine. Higher scores represent worse outcome. These values (collected in identical fashion over 3 months following burn injury) will be entered into a linear mixed model, and the beta coefficient for the race by treatment interaction term will be assessed.
Enrollment of the 90-participant Sample Size During Enrollment Period (Feasibility)
Time Frame: 13 months of enrollment after the first participant
One feasibility measure of this study is demonstrating the ability to recruit 90 patients into the trial within 15 months of enrollment of the first participant. Feasibility of enrollment is defined as the number of potential participants screened for study eligibility versus the number of persons who enrolled in the study.
Secondary Outcomes
No secondary outcomes reported