Chronic Pain Following Thermal Burn Injury Clinical Trial
Official title:
Pilot, Double-blind, Randomized Controlled, Multi-center Study of the Effects of Fish Oil and Vitamin D in the Prevention of Chronic Pain Following Major Thermal Burn Injury
| Verified date | March 2021 |
| Source | University of North Carolina, Chapel Hill |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
The goal of this study is to develop a safe, effective, and readily available treatment that will prevent chronic pain following Major Thermal Burn Injury (MThBI). Burn survivors are prone to develop chronic pain and there is an urgent unmet need for preventative treatments. The preventative treatments proposed for this study, Omega-3 Fatty Acids (O3FA) and Vitamin D have been selected given effectiveness across a range of painful musculoskeletal disorders and their wide availability and low cost. This study is a 2x2 factorial, double-blind, placebo-controlled randomized controlled trial test for the effectiveness of O3FA and Vitamin D to prevent chronic pain development. Burn survivors will be enrolled who have experienced thermal burns that cover less than 30% total body surface area that are severe enough to warrant surgical management, which represents the most common burn injury characteristics. Patients will be enrolled within 72 hours of their burn, and randomized via 1:1:1:1 allocation to receive placebo, O3FA, Vitamin D or both. The investigators will obtain blood samples on enrollment and at 6 weeks to assist in elucidating key mechanisms by which O3FA and Vitamin D reduce chronic pain following MThBI. Chronic pain severity, assessed with a 0-10 numeric rating scale at 6 weeks, 3 months, 6 months and 1 year will be entered into a repeated-measures model. Model estimated contrasts will serve as the primary outcome.
| Status | Terminated |
| Enrollment | 24 |
| Est. completion date | July 31, 2020 |
| Est. primary completion date | July 31, 2020 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years to 65 Years |
| Eligibility | Inclusion Criteria: - = 18 years and = 65 years of age - Admitted to burn center within 72 hours of thermal burn injury - Estimated Total Body Surface area (TBSA) = 30% - Surgical team has plans for surgical management of the burn wound (e.g. xenograft and/or autograft). - Patients experience a thermal burn injury, not an electrical or chemical burn. - Has a telephone to receive follow-up calls. - Able to speak and read English - Resides within 150 miles of study site - Alert and oriented - Willing to take study medication for 6 weeks following enrollment - Subjects are capable of giving informed consent. - Predicted probability of chronic pain = 0.3 when demographic parameters are entered into a logistic regression model developed from a previous cohort. (Initial pain score entered into this model will be based on the highest pain severity over the initial 24 hours of hospital admission). - European American or African American Exclusion Criteria: - Unwilling to take study drug - Allergy to fish oil or corn/soybean oil. - Patient taking clopidogrel (Plavix) - Patient taking warfarin or dabigatran. - Substantial comorbid injury (e.g. long bone fracture) - Pregnancy/Breastfeeding - Prisoner status - Chronic daily opioid use prior to burn (>20 mg oral daily morphine equivalents). - Active psychosis, suicidal ideation, or homicidal ideation - Requires an escharotomy or fasciotomy for the treatment of burn injury. - Has a disorder of pain processing or diminished capacity to perceive pain (congenital insensitivity to pain) - Known Child-Pugh liver disease severity classification B or C. - Known chronic kidney disease stage 4 or higher (GFR=29). - Known Hemophilia A/B - Known bleeding dyscrasia - History of an inability to tolerate fish oil or corn/soybean oil. - Severe gastroesophageal reflux disease - No other history or condition that would, in the investigator's judgment, 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). - Intubated and sedated at time of enrollment. - Hypersensitivity to Vitamin D3, ergocalciferol, calcitriol, alfacalcidol, calcipotriol - Hypercalcemia (if not already completed, this will be assessed by clinical labs with albumin correction prior to enrollment). - Hypervitaminosis - Sarcoidosis - Hyperphosphatemia - Arteriosclerosis - Active myocardial ischemia - Frequent antacid use (calcium carbonate, cimetidine) - Cholestyramine or Colestipol use - Taking Vitamin D supplements in excess of 800 IU daily. - Taking >1g of fish oil per day. |
| Country | Name | City | State |
|---|---|---|---|
| United States | University Of North Carolina | Chapel Hill | North Carolina |
| Lead Sponsor | Collaborator |
|---|---|
| University of North Carolina, Chapel Hill |
United States,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Qualitative Review of Treatment-Related Adverse Events | A primary objective of this pilot study is to ensure safety of both treatments as well as combined. A qualitative review of treatment-related adverse events will be performed and a determination about the degree of relatedness of each adverse event with the intervention using CTCAE criteria will be made as CTCAE criteria assesses relatedness to therapy. Investigator reviewing the details of each adverse event rated the likelihood of relatedness to the study drug on a scale: (unrelated, unlikely, possible, probably, definitely). | 6 weeks following burn injury | |
| Primary | Percent of Participants Who Are Compliant With Follow-up (Feasibility) | The primary objective of this pilot 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 6 weeks following major thermal burn injury. Feasibility is defined as >80% of enrolled participants at 6 weeks following Major Thermal Burn Injury (MThBI). | 6 weeks following burn injury | |
| Primary | By Group Efficacy Estimates Over Year Following Thermal Burn Injury | Estimates of efficacy will be obtained via repeated measures analysis of pain severity over the 1 year 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 you can imagine. Higher scores represent worse outcome. These values (collected in identical fashion over 1 year following burn injury) will be entered into a linear mixed model, and overall effect estimates (beta coefficients) among groups will be determined. Final model was a piece-wise linear mixed model, with a cut-point at 6 weeks. Mixed models were adjusted for age, sex, race, initial pain severity. Every 1 unit change in beta coefficient represents a 1 unit change in pain severity on the 0-10 numeric rating scale. | Over 1 year following MThBI | |
| Secondary | Sex Differences in Treatment Response Based on Pain Scores | Examines existence of gender-based treatment response differences in pain severity measured by a 0-10 numeric rating scale where 0 is no pain and 10 is the most severe pain. Higher scores reflect greater pain (poor outcome). | 6 weeks following burn injury | |
| Secondary | General Mental Health as Measured by the Short Form (SF)-12 General Mental Health Component Scores | Assessment of mental health will be determined by the short form (SF)-12 mental component score. The short form SF-12 Health Survey is a 12-item participant completed questionnaire to measure general health. It includes a mental component score (MCS): ranging from 0 to 100 points. Low values represent a poor health state and high values represent a good mental health. | 6 weeks following burn injury | |
| Secondary | General Physical Health by Treatment Group Measured by the SF-12 General Physical Health Component Scores | Assessment of physical health will be determined by the SF-12 physical component score. The SF-12 Health Survey is a 12 item participant completed questionnaire to measure general health. It includes a physical component score (PCS): ranging from 0 to 100 points. Low values represent a poor physical health and high values represent a good physical health. | 6 weeks following burn injury | |
| Secondary | Pain Interference by Treatment Group Measured by the Brief Pain Inventory | The degree to which pain interferes with important life function will be determined by the Brief Pain Inventory. This is a validated, self-reported scale that measures the severity of pain based on the average pain experienced and assesses impact of pain across 7 domains of life function (e.g., enjoyment of life, relationships, normal work). The total severity scores range from 0 (no interference) to 70 (maximum interference). Higher scores reflect greater pain interference. | 6 weeks following burn injury |