Can Immediate Post-injury Fluoxetine Improve the Recovery Trajectories of Victims in Bodily Trauma?

• ClinicalTrials.gov Identifier: NCT06046859
• Recruitment Status: Recruiting
• First Posted: September 21, 2023
• Last Update Posted: March 15, 2024
• Sponsor: University of Florida
• Information provided by (Responsible Party): University of Florida

Study Description

Brief Summary:

With this prospective double-blinded, placebo controlled clinical trial we hypothesize that immediate (post-injury) intervention with Fluoxetine will prevent/mitigate the development of negative psychiatric symptomology such as PTSD and depression for victims of bodily trauma. We also hypothesize that immediate use of Fluoxetine will decrease subjects' pain, pain interference and opioid use without changing our standard of care post-injury pain medication regimen. Enrolled subjects will be randomized to Fluoxetine or placebo at their index hospitalization.

Condition or disease	Intervention/treatment	Phase
Musculoskeletal Injury	Drug: Fluoxetine; Drug: Placebo	Phase 4

Detailed Description:

Upwards of 40-85% survivors of bodily trauma (in the civilian world most commonly motor vehicle accidents, falls and assaults), develop moderate to severe negative psychiatric symptomology following their injuries. (2,7) This symptomology can persist for years; at least 20% of patients with musculoskeletal trauma, specifically, display symptomology consistent with post-traumatic stress disorder (PTSD) symptomology up to three years following their injury. (8) Poor mental health outcomes are an independent risk factor for poor physical and social outcomes. (9,10) These symptoms, which are highly impairing, are complicated and heightened by loss of work/income following trauma, limited financial and social resources, and a large percentage of the population being uninsured/underinsured. Research has demonstrated that the pressures of poverty and low socioeconomic status alone predispose to PTSD symptomology and poor coping mechanisms, and this is compounded by decreased ability to obtain and pay for mental health care by those impoverished. There are significant barriers to mental health care for many adults, and these hurdles are even more insurmountable for those under or uninsured, minorities, and those in rural communities. (11) Very few victims of trauma who screen positive for psychological disorder receive mental health services following injury (12% at 3-months from injury), and if so, it is far removed from the injury (22% at 24-months from injury).

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 200 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Investigator)
• Masking Description: Researchers collecting survey data will be blinded to patients' intervention status.
• Primary Purpose: Treatment
• Official Title: Can Immediate Post-injury Fluoxetine Improve the Recovery Trajectories of Victims in Bodily Trauma?
• Actual Study Start Date: March 1, 2024
• Estimated Primary Completion Date: November 30, 2026
• Estimated Study Completion Date: November 30, 2026

Arms and Interventions

Arm	Intervention/treatment
Experimental: Subjects randomized to get Fluoxetine therapy; Subjects will be randomized to take Fluoxetine (10mg by mouth per day for first 14 days then 20 mg by mouth for 9 months). The randomized drug will be prescribed by the study team on the day of randomization so that the patient may be monitored for side effects during the remainder of their hospitalization. The patient will be prescribed the randomized medication on the day of discharge and a 90 day supply will be provided by the inpatient research pharmacy at the 2 week, 3 month, and 6 month follow-up visits	Drug: Fluoxetine; Subjects will be randomized to take Fluoxetine (10mg by mouth per day for first 14 days then 20 mg by mouth for 9 months). The randomized drug will be prescribed by the study team on the day of randomization so that the patient may be monitored for side effects during the remainder of their hospitalization. The patient will be prescribed the randomized medication on the day of discharge and a 90 day supply will be provided by the inpatient research pharmacy at the 2 week, 3 month, and 6 month follow-up visits
Active Comparator: Subjects randomized to Placebo; When a patient is enrolled, the inpatient research pharmacy will dispense the appropriately randomized medication in a visually similar, over-encapsulated form as Fluoxetine	Drug: Placebo; When a patient is enrolled, the inpatient research pharmacy will dispense the appropriately randomized medication in a visually similar, over-encapsulated form as Fluoxetine

Outcome Measures

Primary Outcome Measures :

1. Beck Dression Inventory survey, in the post injury period for patients with musculoskeletal trauma. [ Time Frame: Baseline up to 12 months ]
   BDI-II Beck Depression Inventory: higher score means worse outcome; 0-63.

Secondary Outcome Measures :

1. Patient reported pain scores, PROMIS Pain Interference, will be recorded at each visit. [ Time Frame: Baseline up to 12 months ]
   PROMIS PI: Pain Interference; A score of 50 is average; Adaptive so no minimum/maximum values.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 85 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Admitted to UF Health for trauma resulting in:

  • One or more extremity fractures requiring surgery
  • Pelvic Fracture
  • Chest/abdominal Injury requiring intervention in operating room
• Polytrauma (multiple organ systems/multiple fractures) or Beck Depression Inventory (BDI-II) ≥ 14

Exclusion Criteria:

• Severe Traumatic Brain Injury or cognitively not able to participate in surveys. (Glasgow Coma Scale 3-8)
• Other psychiatric conditions on current medical management (SSRI)
• Incarceration or Pregnancy
• Expected Injury Survival of less than 90 days
• Medical or physical condition in opinion of investigators that would preclude safe study participation
• Unable to provide informed consent due to language or other barriers
• Current or previous substance abuse (excluding cannabinoids and alcohol)

Contacts and Locations

Contacts

Contact: Jennifer Hagen, MD; 352-273-7016; hagenje@ortho.ufl.edu

Contact: MaryBeth Horodyski, EdD; 352-273-7074; horodmb@ortho.ufl.edu

Locations

United States, Florida

University of Florida; Recruiting

Gainesville, Florida, United States, 32608

Principal Investigator: Jennifer Hagen, MD

Sponsors and Collaborators

University of Florida

Investigators

• Principal Investigator: Jennifer Hagan, MD; University of Florida

More Information

• Responsible Party: University of Florida
• ClinicalTrials.gov Identifier: NCT06046859
• Other Study ID Numbers: IRB202301506
• First Posted: September 21, 2023
• Last Update Posted: March 15, 2024
• Last Verified: March 2024

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:

Wounds and Injuries; Fluoxetine; Selective Serotonin Reuptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Agents; Serotonin Agents; Physiological Effects of Drugs; Antidepressive Agents, Second-Generation; Antidepressive Agents; Psychotropic Drugs; Cytochrome P-450 CYP2D6 Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Enzyme Inhibitors