Optimized, Neuroplasticity-Enhanced-Depression (ONE-D) Transcranial Magnetic Stimulation (TMS) Treatment for Female Athletes With Co-morbid Depression and Concussion

Optimized, Neuroplasticity Enhanced-Depression (ONE-D) Transcranial Magnetic Stimulation (TMS) Treatment for Female Athletes With Co-morbid Depression and Concussion

Concussion and depression have long been recognized to be intertwined pathologies.1-3 Although female athletes are more likely to suffer from mental health symptoms than males athletes following a concussion,2 research in this area has been largely biased toward males.4 Recently functional MRI (fMRI) studies5 in concussed athletes have established that there are patterns of local alterations in neural connectivity in the frontal cortex that demonstrate anatomic congruency with transcranial magnetic stimulation (TMS) studies that mapped alternations in neural connectivity to functional and somatic symptoms.6 Thus, there is potential that TMS treatment could decrease both symptom profiles, revolutionizing comorbid treatment options. Possible Benefits:

Previous studies have showed a 70% remission rate for depression symptoms. It is possible that participants could have improvement in depressive or concussive symptoms after the ONE-D TMS treatment.

Study Overview

• Status: Not yet recruiting
• Conditions: Depression; Concussion
• Intervention / Treatment: Device: ONE-D TMS protocol and d-cycloserine (125 mg)

Detailed Description

Concussion and depression have long been recognized to be intertwined pathologies.1-3 Although female athletes are more likely to suffer from mental health symptoms than males athletes following a concussion,2 research in this area has been largely biased toward males.4 Recently functional MRI (fMRI) studies5 in concussed athletes have established that there are patterns of local alterations in neural connectivity in the frontal cortex that demonstrate anatomic congruency with transcranial magnetic stimulation (TMS) studies that mapped alternations in neural connectivity to functional and somatic symptoms.6 Thus, there is potential that TMS treatment could decrease both symptom profiles, revolutionizing comorbid treatment options.

The objective of this application is to treat female athletes with depression and concussion with the Optimized, Neuroplasticity-Enhanced techniques in Depression (ONE-D) protocol.7 This is an innovative, one-day duration TMS treatment for depression. We propose to utilize tradition depression assessments, such as the Patient Health Questionnaire 9 (PHQ-9)8, as well as athlete-specific symptom inventories, including the Post-Concussion Symptom Scale (PCSS)9 and the Sport Mental Health Assessment Tool 1 (SMHAT-1)10 surveys to test our central hypothesis that female athletes with a history of concussion and depression will experience symptom improvement in depression inventories as well as athlete-specific symptom domains. We will assess associations between TMS treatment and depression through PHQ-9 and SMHAT-1 and associations between TMS treatment and concussion symptoms through PCSS.

Treatment Delivery

Once the subject completes the consent process, they will begin the ONE-D TMS protocol.9 The protocol consists of pharmacologic neural priming via a single dose of orally dissolving d-cycloserine (125 mg).The UF-World Equestrian center (WEC) pharmacy will dispense this medication prior to the study visit. The WEC pharmacy is located in the same physical building as the clinic where the treatment will take place. Patients will obtain their medication from the pharmacy prior to their treatment appointment. The medications will be consumed one hour (50-70 min) prior to the start of the first treatment under study staff supervision. After consuming the medication, the participant will begin baseline symptom inventory scores, including Sport Concussion Office Assessment Tool 6 (SCOAT6), Post-Concussion Symptom Scale (PCSS), Patient Health Questionnaire 9 (PHQ-9) and the Sport Mental Health Assessment Tool 1 (SMHAT-1).18 The treatment protocol consists of an AMPA device delivering accelerate theta-burst stimulation for a total of 600 pulses over 3 minute sessions.9 The treatment is repeated every 30 minutes (± 3 min) for a total of 20 sessions over 9.5 hours in a single day. The treatment will be performed by the research assistant or the research coordinator under PI supervision.

The Ampa TMS system was selected for this study as it uses anatomic locations to guide treatment targets, as opposed to other commercially available TMS systems that require FMRI imaging to create individual treatment plans. AMPS technology is FDA approved to be utilized in this manner.

Treatment parameters:

• 3 Hz x 600 pulses
• 90% of motor threshold for contralateral upper extremity

Symptom inventories will be recorded at weeks 3, 6, and 12 after the treatment session. The surveys will be collected through Redcap. Due to the nature of the surveys, the subjects will be called by a member of the research team during business hours so that if any subject is deemed positive for suicidality, the research team can immediately contact the PI and refer patient to treatment as stated in DSMB/DSMP. This may include a 911 welfare check. At the 12-week mark, the subjects will be called via zoom video call to complete the SCOAT6.

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• Study Type: Interventional
• Enrollment (Estimated): 35
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Sara Gould, MD; Phone Number: 352-273-7381; Email: gouldsj@ortho.ufl.edu
• Study Contact Backup: Name: Virginia Dykes, DAT,LAT,ATC; Phone Number: 352-273-7343; Email: jacksve@ortho.ufl.edu

Study Locations

• United States
  • Florida
    • Ocala, Florida, United States, 34482
      • UF World Equestrian Center
      • Contact: Sara Gould, MD; Phone Number: 352-273-7381; Email: gouldsj@ortho.ufl.edu
      • Contact: Virginia Dykes, DAT,LAT,ATC; Phone Number: 352-273-7343; Email: jacksve@ortho.ufl.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Female athletes, both recreational and professional
• ages 18-65 years old
• Concussion as determined by clinical history (at least 72 hours post-diagnosis) and Post-Concussion Symptom Scale (PCSS) score above 7 OR more than 4 total symptoms present
• Depression as determined by Patient Health Questionnaire - (PHQ-9) score of 10 or greater indicating moderate depression or greater
• Treatment-resistant depression as determined by previously taken or currently taking an oral antidepressant for at least 6 weeks

Exclusion Criteria:

• Pregnant or breast-feeding individuals
• History of seizures or epilepsy
• Implanted devices (such as cochlear implants, brain stimulators, aneurysm clips or stents)
• Participants undergoing treatment with ototoxic medications (aminoglycosides, cisplatin)
• History of bipolar disorder
• Pacemakers or implanted defibrillators
• Allergy or other contraindications to d-cycloserine
• Other contraindications as determined by PI
• Unable to provide informed consent due to language or other barriers
• Incarceration
• Biological male gender

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Female athletes with a history of concussion and depression; Participants are treated with ONE-D TMS protocol.9 The protocol consists of pharmacologic neural priming via a single dose of orally dissolving d-cycloserine (125 mg).	Device: ONE-D TMS protocol and d-cycloserine (125 mg); Begin the ONE-D TMS protocol.9 The protocol consists of pharmacologic neural priming via a single dose of orally dissolving d-cycloserine (125 mg).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient Health Questionnaire 9 (PHQ-9) depression symptom inventory scores	These inventories track not only mental health symptoms, but also somatic symptoms that can be affected by depression, including sleep and athletic performance.	Baseline, 12 weeks
Sport Mental Health Assessment Tool 1 (SMHAT-1) depression symptom inventory scores	These inventories track not only mental health symptoms, but also somatic symptoms that can be affected by depression, including sleep and athletic performance.	Baseline, 3 weeks, 6 weeks, 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Post-Concussion Symptom Scale (PCSS) inventory of concussion symptoms	This inventory monitors concussion symptoms	Baseline, 12 weeks
Sport Concussion Office Assessment Tool 6 (SCOAT6) inventory scores	This inventory monitors post-concussion symptoms	Baseline, 3 weeks, 6 weeks, 12 weeks

Collaborators and Investigators

• Sponsor: University of Florida
• Investigators: Principal Investigator: Sara Gould, MD, University of Florida

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): June 1, 2028

Study Registration Dates

• First Submitted: March 27, 2026
• First Submitted That Met QC Criteria: March 27, 2026
• First Posted (Actual): April 2, 2026

Study Record Updates

• Last Update Posted (Actual): April 2, 2026
• Last Update Submitted That Met QC Criteria: March 27, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Injuries, Traumatic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Behavioral Symptoms; Craniocerebral Trauma; Trauma, Nervous System; Head Injuries, Closed; Wounds, Nonpenetrating; Brain Injuries; Behavior; Depression; Brain Concussion
• Other Study ID Numbers: IRB202600155

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes