A Phase 2 interventional study of Fluoxetine and Calcium in Musculoskeletal Injury, sponsored by University of Florida. Completed at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-05-14.
Sponsored by University of Florida · Phase 2, Interventional, and Treatment
Musculoskeletal trauma is one of the leading causes of disability in the United States and its negative quality of life impact extends beyond that of physical recovery. More than 50% of victims of musculoskeletal trauma suffer lasting mental health issues following their injury. These symptoms can develop across all spectrums of patients with a variety of injury severities. Previously, this research team developed a ten-step program with the aim of developing fostering coping mechanisms in trauma patients. We were unable to demonstrate a measurable benefit to their mental health or physical function. This has been mirrored in other studies as well; talk therapy and support groups are not a strong enough intervention for some patients.
We hypothesize that a subset of the trauma population would benefit from medical treatment for their depressive and anxious symptoms in the early recovery period. Given the limited resources of mental health systems, it would be ideal for their surgical providers to be able to manage safely their post-injury mental health issues during their surgical follow up. This is a pragmatic pilot study to develop an effective, acceptable, time-limited treatment strategy that could be safely implemented by non-mental health care providers for victims of musculoskeletal trauma.
Rationale
Over 50% of victims of musculoskeletal trauma suffer prolonged depressive and anxious symptomology following their initial injury. This is an independent risk factor for prolonged mental and physical disability. In previous research by the study team in orthopedic trauma patients without previous diagnosis of psychiatric illness, we have demonstrated 28% of these patients had depressive symptomology and 40% had anxiety symptomology 3 months following their traumatic injury. [1] Mental health resources are limited, placing the bulk of patient care on the orthopedic surgeons and primary care physicians. Support groups, self-help programs and talk therapy, while valuable, have not demonstrated measurable efficacy for this patient population. We hypothesize that a subset of the trauma population would benefit from medical treatment for their depressive and anxious symptoms in the early recovery period.
Specific Aims
Aim 1: Evaluate the efficacy of immediate Fluoxetine therapy versus standard of care Calcium treatment in improving mental health and wellbeing in the post-injury period for patients with musculoskeletal trauma.
Hypothesis: Patients randomized to Fluoxetine will have less severe depression, anxiety and post-traumatic stress symptoms than those treated with calcium.
Methodology: Patients >18 years of age admitted to UF Health with extremity fracture(s) resulting from high energy trauma (more than ground level fall) will be enrolled during their index hospitalization. Baseline mental well-being surveys will be obtained (Table 1) and patients will be randomized to calcium supplementation or Fluoxetine. The medications will be started during the hospitalization and prescribed upon discharge. The patient will be followed in the orthopedic clinic on a standard of care post-operative schedule (2 weeks, 3 months, 6 months, and 12 months). Serial mental well-being surveys will be administered at these time points. Post-operative complications such as infection, nonunion or any other reason for return to the operating room will be tracked.
Aim 2: Develop a safe Fluoxetine treatment protocol with a goal to be therapeutic by 6 weeks and taper completely off of treatment by 6-12 months.
Hypothesis: We will be able to develop a standardized, time-limited protocol that could feasibly be utilized by non-mental health providers.
Methodology: Dr. Barbosa De Faria will monitor symptoms and side effects of the Fluoxetine treatment study arm. Any evidence of escalation of depressive or suicidal ideology in either study population will result in immediate psychiatric treatment. Common side effects, medication adherence and appropriate discontinuation will be tracked. Patient reported pain scales will be obtained at each clinic visit as well as documentation of narcotic and cannabis pain treatment during recovery. Patients will be informed of the finite nature of the medical management. We will assess how many patients in the Fluoxetine arm report worsening of symptomology after the cessation of therapy at 9 months and how many seek continued management.
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Exclusion Criteria:
Subjects will be randomized to take Fluoxetine (10mg by mouth per day). The randomized drug will be prescribed by the orthopedic team on the day 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.
Drug: Fluoxetine
Subjects will be randomized to take Calcium supplementation (1000mg by mouth per day). The randomized drug will be prescribed by the orthopedic team on the day 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.
Drug: Calcium
Subjects will be randomized to take Fluoxetine (10mg by mouth per day). The randomized drug will be prescribed by the orthopedic team on the day 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.
Subjects will be randomized to take Calcium supplementation (1000mg by mouth per day). The randomized drug will be prescribed by the orthopedic team on the day 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.
BDI-II - Beck Depression Inventory-II
Score range 0-63. Higher scores indicate worse outcomes, reflecting greater severity of depressive symptoms.
Time frame: Baseline, 2 weeks, 6 weeks,3 months, 6 months, 1 year
BAI - Beck Anxiety Inventory
Score range 0-63. Higher scores indicate worse outcomes, reflecting greater severity of anxiety symptoms.
Time frame: Baseline, 2 weeks, 6 weeks, 3 months, 6 months, 1 year
PSQI - Pittsburgh Sleep Quality Index
Score range 0-21. Higher scores indicate worse outcomes, representing poorer sleep quality.
Time frame: 2 weeks, 6 weeks, 3 months
PSS-SR5 - PTSD Symptom Scale-Self-Report for DSM-5
Score range 0-80. Higher scores indicate worse outcomes, representing greater PTSD symptom severity.
Time frame: Baseline, 2 weeks, 6 weeks, 6 months, 1 year
PROMIS Social Isolation - Patient-Reported Outcomes Measurement Information System
Scores are typically reported as T-scores, which generally range from about 20-80 (population mean = 50, standard deviation = 10). Higher scores indicate worse outcomes, meaning greater perceived social isolation, a higher PROMIS Social Isolation score reflects feeling more isolated, excluded, or disconnected from others, while lower scores indicate better social connectedness and less isolation.
Time frame: 6 weeks, 3 months,6 months, 1 year
PEG - Pain, Enjoyment of Life, and General Activity Scale
Score range 0-10. Higher scores indicate worse outcomes, representing greater pain intensity and interference with enjoyment of life and general activity.
Time frame: Baseline, 2 weeks, 6 weeks, 3 months, 6 months, 1 year
| Milestone | Subjects Randomized to Get Fluoxetine Therapy | Subjects Randomized to Get Calcium Supplmentation |
|---|---|---|
| Started | 22 | 33 |
| Completed | 13 | 17 |
| Not completed | 9 | 16 |
Score range 0-63. Higher scores indicate worse outcomes, reflecting greater severity of depressive symptoms.
| units on a scale | Subjects Randomized to Get Fluoxetine Therapy | Subjects Randomized to Get Calcium Supplmentation |
|---|---|---|
| Baseline | 11.4 ± 7.4 | 12.8 ± 15.3 |
| 2 weeks | 9.6 ± 8.9 | 11.5 ± 11.6 |
| 6 weeks | 8.1 ± 6.4 | 12.2 ± 12.9 |
| 3 months | 11.1 ± 12.6 | 7.5 ± 8.9 |
| 6 months | 7.2 ± 11.2 | 11.9 ± 15.5 |
| 1 year | 7.9 ± 11 | 9.1 ± 11 |
Score range 0-63. Higher scores indicate worse outcomes, reflecting greater severity of anxiety symptoms.
| units on a scale | Subjects Randomized to Get Fluoxetine Therapy | Subjects Randomized to Get Calcium Supplmentation |
|---|---|---|
| Baseline | 12.7 ± 12.2 | 11.5 ± 9.9 |
| 2 weeks | 9.9 ± 10.3 | 12.5 ± 10 |
| 6 weeks | 10.5 ± 10.5 | 10.8 ± 11.2 |
| 3 months | 10.8 ± 12.6 | 9 ± 10.2 |
| 6 months | 7.9 ± 12.3 | 12.4 ± 12.6 |
| 1 year | 9.7 ± 12.9 | 8.9 ± 8.1 |
Score range 0-21. Higher scores indicate worse outcomes, representing poorer sleep quality.
| units on a scale | Subjects Randomized to Get Fluoxetine Therapy | Subjects Randomized to Get Calcium Supplmentation |
|---|---|---|
| 2 weeks | 7 ± 4.1 | 9.4 ± 5.3 |
| 6 weeks | 7.1 ± 4.8 | 7.3 ± 4.4 |
| 3 months | 7.1 ± 4.8 | 6.6 ± 4.7 |
Score range 0-80. Higher scores indicate worse outcomes, representing greater PTSD symptom severity.
| units on a scale | Subjects Randomized to Get Fluoxetine Therapy | Subjects Randomized to Get Calcium Supplmentation |
|---|---|---|
| Baseline | 21.9 ± 17.2 | 15.1 ± 16 |
| 2 weeks | 15.9 ± 16.4 | 19.3 ± 18.2 |
| 6 weeks | 14.8 ± 15.1 | 17.3 ± 19.5 |
| 6 months | 11.1 ± 18.5 | 15.5 ± 18.7 |
| 1 year | 10.5 ± 15.1 | 19.9 ± 21.1 |
Scores are typically reported as T-scores, which generally range from about 20-80 (population mean = 50, standard deviation = 10). Higher scores indicate worse outcomes, meaning greater perceived social isolation, a higher PROMIS Social Isolation score reflects feeling more isolated, excluded, or disconnected from others, while lower scores indicate better social connectedness and less isolation.
| units on a scale | Subjects Randomized to Get Fluoxetine Therapy | Subjects Randomized to Get Calcium Supplmentation |
|---|---|---|
| 6 weeks | 43.7 ± 9.4 | 47.7 ± 8.4 |
| 3 months | 45.9 ± 9.5 | 49 ± 9.6 |
| 6 months | 50.8 ± 8 | 47.8 ± 8.4 |
| 1 year | 54.3 ± 10.1 | 48.9 ± 7.9 |
Score range 0-10. Higher scores indicate worse outcomes, representing greater pain intensity and interference with enjoyment of life and general activity.
| units on a scale | Subjects Randomized to Get Fluoxetine Therapy | Subjects Randomized to Get Calcium Supplmentation |
|---|---|---|
| Baseline | 5.7 ± 3.6 | 4.9 ± 3.7 |
| 2 weeks | 5.3 ± 3 | 6.1 ± 2.8 |
| 6 weeks | 3.9 ± 3.1 | 4.2 ± 2.9 |
| 3 months | 4.3 ± 2.5 | 4.6 ± 3.1 |
| 6 months | 2.7 ± 2.3 | 4 ± 2.8 |
| 1 year | 3 ± 2.8 | 4.9 ± 3.1 |
Collected over From baseline thru 1 year post hospital discharge. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Subjects Randomized to Get Fluoxetine Therapy | 0/22 (0%) | 0/22 (0%) | 0/22 (0%) |
| Subjects Randomized to Get Calcium Supplmentation | 0/33 (0%) | 0/33 (0%) | 0/33 (0%) |
| Age, Categorical(Participants) | Subjects Randomized to Get Fluoxetine Therapy | Subjects Randomized to Get Calcium Supplmentation | Total |
|---|---|---|---|
| <=18 years | 0 | 0 | 0 |
| Between 18 and 65 years | 20 | 29 | 49 |
| >=65 years | 2 | 4 | 6 |
| Age, Continuous(Years) | Subjects Randomized to Get Fluoxetine Therapy | Subjects Randomized to Get Calcium Supplmentation | Total |
|---|---|---|---|
| Mean | 40.3 ± 17.7 | 43.5 ± 15.8 | 41.9 ± 16.75 |
| Sex: Female, Male(Participants) | Subjects Randomized to Get Fluoxetine Therapy | Subjects Randomized to Get Calcium Supplmentation | Total |
|---|---|---|---|
| Female | 12 | 14 | 26 |
| Male | 10 | 19 | 29 |
| Race and Ethnicity Not Collected(Participants) | Subjects Randomized to Get Fluoxetine Therapy | Subjects Randomized to Get Calcium Supplmentation | Total |
|---|---|---|---|
| Count of participants | — | — | 0 |
| Region of Enrollment(Participants) | Subjects Randomized to Get Fluoxetine Therapy | Subjects Randomized to Get Calcium Supplmentation | Total |
|---|---|---|---|
| United States | 22 | 33 | 55 |
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