Musculoskeletal InjuryPhase 2NCT04850222
Fluoxetine Mitigation Mental Health Study for Patients With Musculoskeletal Trauma
A Phase 2 study testing Fluoxetine and Calcium in people with Musculoskeletal Injury, run by University of Florida at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Musculoskeletal Injury
- What is being tested?
- Fluoxetine and Calcium
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 55 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Sep 2021to 17 Feb 2025
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- patients 18 and older under the care of the UF Orthopedic Trauma Division admitted to UF Health for trauma resulting in one or more extremity or pelvic fractures requiring surgery will be screened.
Who cannot join
- patients with Traumatic Brain Injury or a past medical history of bipolar or other mental health conditions on current medical management will be excluded
- patients unlikely to follow up (live in at a distance from Gainesville, incarcerated etc.) will also be excluded.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Can Fluoxetine Mitigate the Mental Health Decline Seen in Patients With Musculoskeletal Trauma?
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.
Read the detailed description
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.
- Conditions
- Musculoskeletal Injury
- Being tested
- Fluoxetine, Calcium
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FluoxetineDrug
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.
CalciumDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Subjects randomized to get Fluoxetine therapy | Experimental | 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. Receives: Drug: Fluoxetine |
| Subjects randomized to get Calcium Supplmentation | Active comparator | 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. Receives: Drug: Calcium |
What is being measured
The primary outcome is the main question the study is designed to answer.
BDI-II - Beck Depression Inventory-II
Score range 0-63. Higher scores indicate worse outcomes, reflecting greater severity of depressive symptoms.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 6 weeks, 3 months,6 months, 1 year
Secondary outcomes (1)
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.
Measured: Baseline, 2 weeks, 6 weeks, 3 months, 6 months, 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Apr 2021
- Study start1 Sep 2021
- Primary completion17 Feb 2025
- Study completion17 Feb 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Musculoskeletal InjuryStudies of the same condition, open and under way.
- More trials run by University of FloridaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Investigator
- Enrolment
- 55 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Florida
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jennifer Hagen, MD, Principal investigator, University of Florida
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04850222
- Sponsor's protocol ID
- IRB202100808
- Other IDs
- OCR40926
- Status last verified
- Aug 2025
- First submitted
- 14 Apr 2021
- Last updated
- 14 May 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Lossada-Soto E, Pazik M, Horodyski MB, Vasilopoulos T, de Faria LB, Mathews C, Hagen J. Can fluoxetine mitigate mental health decline in musculoskeletal trauma patients: a pilot single-center randomized clinical trial. Pilot Feasibility Stud. 2022 Aug 17;8(1):184. doi: 10.1186/s40814-022-01119-8.
PubMed 35978446
Study at a glance
From the registry record, last updated by the sponsor on 14 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Can Fluoxetine Mitigate the Mental Health Decline Seen in Patients With Musculoskeletal Trauma?
- ClinicalTrials.gov ID
- NCT04850222
- Acronym / sponsor ID
- IRB202100808
- Conditions
- Musculoskeletal Injury
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 55 participants (actual)
- Lead sponsor
- University of FloridaUniversity, hospital or other
- Study start
- 1 Sep 2021 (actual)
- Primary completion
- 17 Feb 2025 (actual)
- Study completion
- 17 Feb 2025 (actual)
- First posted
- 20 Apr 2021 (actual)
- Results
- Posted 14 Apr 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Subjects randomized to get Fluoxetine therapy | Experimental | Drug: FluoxetineSubjects 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 randomized to get Calcium Supplmentation | Active comparator | Drug: CalciumSubjects 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- patients 18 and older under the care of the UF Orthopedic Trauma Division admitted to UF Health for trauma resulting in one or more extremity or pelvic fractures requiring surgery will be screened.
Key exclusion criteria (2 listed)
- patients with Traumatic Brain Injury or a past medical history of bipolar or other mental health conditions on current medical management will be excluded
- patients unlikely to follow up (live in at a distance from Gainesville, incarcerated etc.) will also be excluded.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| FluoxetineSubjects 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 | Subjects randomized to get Fluoxetine therapy |
| CalciumSubjects 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 | Subjects randomized to get Calcium Supplmentation |
Primary outcome
BDI-II - Beck Depression Inventory-II
Time frame: Baseline, 2 weeks, 6 weeks,3 months, 6 months, 1 year
Score range 0-63. Higher scores indicate worse outcomes, reflecting greater severity of depressive symptoms.
BAI - Beck Anxiety Inventory
Time frame: Baseline, 2 weeks, 6 weeks, 3 months, 6 months, 1 year
Score range 0-63. Higher scores indicate worse outcomes, reflecting greater severity of anxiety symptoms.
PSQI - Pittsburgh Sleep Quality Index
Time frame: 2 weeks, 6 weeks, 3 months
Score range 0-21. Higher scores indicate worse outcomes, representing poorer sleep quality.
PSS-SR5 - PTSD Symptom Scale-Self-Report for DSM-5
Time frame: Baseline, 2 weeks, 6 weeks, 6 months, 1 year
Score range 0-80. Higher scores indicate worse outcomes, representing greater PTSD symptom severity.
PROMIS Social Isolation - Patient-Reported Outcomes Measurement Information System
Time frame: 6 weeks, 3 months,6 months, 1 year
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.
1 secondary outcome
PEG - Pain, Enjoyment of Life, and General Activity Scale
Time frame: Baseline, 2 weeks, 6 weeks, 3 months, 6 months, 1 year
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 May 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 35978446Lossada-Soto E, Pazik M, Horodyski MB, Vasilopoulos T, de Faria LB, Mathews C, Hagen J. Can fluoxetine mitigate mental health decline in musculoskeletal trauma patients: a pilot single-center randomized clinical trial. Pilot Feasibility Stud. 2022 Aug 17;8(1):184. doi: 10.1186/s40814-022-01119-8.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jennifer Hagen, MD principal investigator
University of Florida
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Fluoxetine and Calcium in people with Musculoskeletal Injury, run by University of Florida at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 14 Apr 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
BDI-II - Beck Depression Inventory-II (time frame: Baseline, 2 weeks, 6 weeks,3 months, 6 months, 1 year). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04850222, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 May 2026.