rTMS Dosing for Depression Post-Spinal Cord Injury

Overseen By Catherine J VanDerwerker, PhD DPT PT

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: VA Office of Research and Development

Must not be taking: Antidepressants, Anti-seizure, others

Disqualifiers: Neurologic diseases, Dementia, Psychosis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 32

Duration: 6 weeks

24 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new application of rTMS (Repetitive Transcranial Magnetic Stimulation) for treating depression in individuals with spinal cord injury (SCI). The goal is to determine if this method is more effective than the current approach, which some SCI patients cannot use properly due to arm or hand issues. The study involves two groups: one receives real rTMS, while the other receives a placebo (a treatment that appears real but is not). It is suitable for individuals who have had a spinal cord injury for at least six months, are experiencing major depression, and have not changed their depression medications in the past month. As an unphased trial, this study provides a unique opportunity to contribute to innovative research that could enhance treatment options for SCI-related depression.

Will I have to stop taking my current medications?

The trial requires that you are not taking antidepressant medications or that there has been no change in doses of psychotropic medications for at least 4 weeks before the study (6 weeks if you started a new medication).

What prior data suggests that this technique is safe for individuals with depression post-spinal cord injury?

Studies have shown that repetitive transcranial magnetic stimulation (rTMS) is generally well-tolerated for treating depression. The FDA has approved this treatment for depression, supporting its safety. Research indicates that most people experience only mild side effects, such as slight headaches or scalp discomfort, while serious side effects are rare. For individuals with spinal cord injuries (SCI), early findings suggest rTMS can be used safely to aid recovery, though its use is still under investigation. Overall, the safety of rTMS makes it a promising option for those considering this treatment. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about repetitive transcranial magnetic stimulation (rTMS) for depression following a spinal cord injury because it offers a novel approach compared to traditional treatments like medication or psychotherapy. rTMS uses magnetic fields to stimulate nerve cells in the brain, which could potentially address depression more directly and quickly than medications that often take weeks to show effects. Additionally, rTMS is non-invasive and tailored to the individual's needs using reverse-calculation electric-field modeling, which could enhance its effectiveness and reduce side effects. This personalized and targeted method represents a promising advancement in managing depression in this specific patient group.

What evidence suggests that this trial's treatments could be effective for depression post-SCI?

Research shows that repetitive transcranial magnetic stimulation (rTMS) effectively treats depression. The FDA has approved it for this purpose, indicating its effectiveness for many people. For those with spinal cord injuries (SCI), rTMS has also shown promise in improving movement and reducing pain. This trial will compare two approaches: Active rTMS, administered 5 days a week for 6 weeks, and Sham rTMS, which uses a sham treatment coil to simulate the procedure without delivering active treatment. Early studies suggest that a new method of administering rTMS might benefit those with SCI who cannot use the current thumb-involved method. This could make rTMS more accessible and effective for people with depression after an SCI. ^{2 3 6 7 8}

Who Is on the Research Team?

Catherine VanDerwerker, PT DPT PhD

Principal Investigator

Ralph H. Johnson VA Medical Center, Charleston, SC

Are You a Good Fit for This Trial?

This trial is for adults aged 18-60 with major depressive disorder and a spinal cord injury (cervical or thoracic) of at least 6 months duration. Candidates should not be on antidepressants, or have stable doses for at least 4 weeks. They must not have cognitive impairments, psychosis, metallic implants, seizure history, pregnancy, high suicide risk, other neurological disorders/dementia or claustrophobia.

Inclusion Criteria

Hamilton Depression Rating Scale-17 score greater than 18

I have been diagnosed with major depressive disorder.

I haven't changed my mental health medication doses for at least 4 weeks.

Exclusion Criteria

Cognitive impairment (Montreal Cognitive Assessment score less than 17)

History of psychosis or other primary Axis I disorder

Presence of electronic or metallic implants (e.g., metal in the head, cochlear implant, or pacemaker)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either active or sham rTMS treatment for depression post-SCI, administered 5 days/week for 6 weeks

6 weeks

30 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments at 12 and 24 weeks post-intervention

24 weeks

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• rTMS

Trial Overview The study tests a new way to dose repetitive transcranial magnetic stimulation (rTMS), an FDA-approved depression treatment that doesn't rely on thumb movement responses—important for those with arm/hand impairment post-spinal cord injury. It compares active rTMS against sham (placebo-like) treatment to assess its effect on depression in these individuals.

How Is the Trial Designed?

Group I: Active rTMS Experimental Treatment 1 Intervention

Active repetitive transcranial magnetic stimulation (rTMS) that will be administered 5 days/week for 6 weeks. Intensity will be individualized based on reverse-calculation electric-field modeling.

Group II: Sham rTMS Placebo Group 1 Intervention

Sham repetitive transcranial magnetic stimulation (rTMS) that will be administered 5 days/week for 6 weeks. Intensity will be individualized based on reverse-calculation electric-field modeling, but a sham treatment coil will be used; thus, no active treatment will be administered.

rTMS is already approved in United States, European Union for the following indications:

Approved in United States as rTMS for:

• Obsessive-Compulsive Disorder (OCD)
• Major Depressive Disorder
• Migraines
• Smoking cessation

Approved in European Union as rTMS for:

• Obsessive-Compulsive Disorder (OCD)
• Major Depressive Disorder

Who Is Running the Clinical Trial?

VA Office of Research and Development

Lead Sponsor

Trials

1,691

Recruited

3,759,000+

Published Research Related to This Trial

A case study of a 71-year-old stroke survivor showed that repetitive transcranial magnetic stimulation (rTMS) significantly reduced depression symptoms after 10 sessions, indicating its efficacy for post-stroke depression.

Ongoing maintenance rTMS treatments helped sustain the improvements in depressive symptoms for at least 3 months after the initial treatment, suggesting that continued therapy may enhance long-term benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Extended Repetitive Transcranial Magnetic Stimulation Therapy for Post-stroke Depression in a Patient With a Pre-frontal Cortical Lesion: A Case Study. Hordacre, B., Chau, A., Graetz, L., et al.[2022]

Repetitive transcranial magnetic stimulation (rTMS) has been explored as a noninvasive method to enhance recovery of motor and sensory functions in patients with spinal cord injury (SCI), but results have been mixed, with some studies showing improvements while others did not.

The effectiveness of rTMS may depend on specific parameters of the treatment and the extent of post-injury reorganization in the nervous system, indicating a need for more research to optimize its use in rehabilitation for SCI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of repetitive transcranial magnetic stimulation on recovery of function after spinal cord injury. Tazoe, T., Perez, MA.[2021]

In a pilot trial with 29 participants suffering from major depressive disorder, different doses of repetitive transcranial magnetic stimulation (rTMS) were tested, showing that all doses led to significant reductions in depression severity after 4 weeks, with no serious adverse events reported.

The highest dose of 4000 pulses showed the most substantial improvement in depression scores during the first two weeks, suggesting that higher doses may lead to a quicker antidepressant effect, warranting further investigation in a larger definitive trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation in major depression: A three-arm parallel-group dose-response randomized pilot trial. Johansson, K., Adler, M., Båve, U., et al.[2023]

A study of 77 military patients receiving rTMS treatment showed significant reductions in depression and PTSD symptoms, with over 44% of patients experiencing a notable decrease in depression scores after treatment.

Most patients had previously tried multiple antidepressants (average of 2.7 trials), indicating that rTMS may be an effective alternative for those with treatment-resistant depression and comorbid PTSD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impacts of rTMS on Refractory Depression and Comorbid PTSD Symptoms at a Military Treatment Facility. Wilkes, S., Ona, C., Yang, M., et al.[2021]

In a study involving 300 patients with treatment-resistant depression, different doses of repetitive transcranial magnetic stimulation (rTMS) did not show significant differences in response rates, with all groups exceeding a 45% response rate.

While increasing the number of TMS pulses did not correlate with better overall outcomes, higher doses of left-sided rTMS were associated with improved remission rates when considering the duration of illness, suggesting that other factors may influence treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A pragmatic randomized controlled trial exploring the relationship between pulse number and response to repetitive transcranial magnetic stimulation treatment in depression. Fitzgerald, PB., Hoy, KE., Reynolds, J., et al.[2020]

In a study involving subjects with spinal cord injury (SCI), real repetitive transcranial magnetic stimulation (rTMS) did not show significant differences in the ASIA impairment scale compared to sham treatment, indicating limited efficacy in this specific measure.

However, rTMS did lead to short-term improvements in upper limb function as measured by the Action Research Arm Test (ARAT) and increased motor thresholds, suggesting that electrophysiological measures could be valuable in assessing functional changes in SCI patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Action of 5 Hz repetitive transcranial magnetic stimulation on sensory, motor and autonomic function in human spinal cord injury. Kuppuswamy, A., Balasubramaniam, AV., Maksimovic, R., et al.[2011]

In a study involving 60 rats with partial spinal cord injury, the combination of repetitive transcranial magnetic stimulation (rTMS) and treadmill training (TT) significantly improved motor function compared to other treatment groups, indicating enhanced recovery.

The combined rTMS and TT treatment also led to increased levels of brain-derived neurotrophic factor (BDNF), synapsin I (SYN), and postsynaptic density protein-95 (PSD-95) in both the motor cortex and spinal cord, suggesting that this approach promotes neuroplasticity essential for motor recovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Repetitive Transcranial Magnetic Stimulation (rTMS) and Treadmill Training on Recovery of Motor Function in a Rat Model of Partial Spinal Cord Injury. Wang, P., Yin, R., Wang, S., et al.[2022]

Repetitive transcranial magnetic stimulation (rTMS) shows promise as a non-invasive treatment to enhance recovery and functional outcomes in individuals with spinal cord injury (SCI), with potential benefits for motor function and spasticity based on a review of 16 studies.

Future research should focus on optimizing rTMS parameters, such as timing and dosage, and emphasize the need for more rigorous studies comparing real versus sham rTMS to strengthen the evidence for its efficacy in SCI rehabilitation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stimulation Parameters Used During Repetitive Transcranial Magnetic Stimulation for Motor Recovery and Corticospinal Excitability Modulation in SCI: A Scoping Review. Brihmat, N., Allexandre, D., Saleh, S., et al.[2022]

High-frequency repetitive transcranial magnetic stimulation (rTMS) significantly improved lower extremities motor score (LEMS) and various gait parameters in 17 patients with motor incomplete spinal cord injury after 15 sessions, with effects lasting for at least 2 weeks.

The active rTMS group showed notable improvements in spasticity and gait metrics, while the sham group did not demonstrate significant changes, highlighting the efficacy of rTMS as a therapeutic intervention for enhancing motor function in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Motor and gait improvement in patients with incomplete spinal cord injury induced by high-frequency repetitive transcranial magnetic stimulation. Benito, J., Kumru, H., Murillo, N., et al.[2021]

In a proof-of-concept study involving three adults with cervical spinal cord injury, repetitive QuadroPulse transcranial magnetic stimulation (rTMS(QP)) showed functional benefits, particularly in improving walking speed and cortical excitability without any adverse effects.

The combination of rTMS(QP) with targeted exercises led to even greater improvements in motor function, suggesting that this approach could be effective and warrants further investigation in larger studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of QuadroPulse rTMS for improving motor function after spinal cord injury: Three case studies. Alexeeva, N., Calancie, B.[2018]

Repetitive transcranial magnetic stimulation (rTMS) can be safely administered to individuals with traumatic brain injury (TBI) when following specific guidelines, minimizing risks such as seizures.

In a case study of a 48-year-old man with severe TBI, rTMS treatment for post-TBI depression over 6 weeks led to a 49% reduction in depression symptoms, demonstrating its potential efficacy in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preliminary guidelines for safe and effective use of repetitive transcranial magnetic stimulation in moderate to severe traumatic brain injury. Nielson, DM., McKnight, CA., Patel, RN., et al.[2022]

High-frequency repetitive transcranial magnetic stimulation (rTMS) applied to the leg motor area significantly reduced lower limb spasticity in patients with incomplete spinal cord injury, with effects lasting for at least one week after treatment.

The study involved 15 patients who underwent 5 days of rTMS sessions, showing that active stimulation led to clinical improvements compared to sham stimulation, although neurophysiological measures did not show changes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reduction of spasticity with repetitive transcranial magnetic stimulation in patients with spinal cord injury. Kumru, H., Murillo, N., Samso, JV., et al.[2021]

Citations

1. reporter.nih.gov reporter.nih.gov/project-details/10977065

Project Details [This study specifically addresses current limitations in treating depression post- SCI using rTMS and will: (1) identify the target electric-field (e-field) ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S2772529425000530

nTMS in spinal cord injury: Current evidence, challenges ... nTMS has shown encouraging preliminary results in both clinical assessment and rehabilitation (motor and pain) of patients with SCI.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7526137/

Effects of Repetitive Transcranial Magnetic Stimulation on ... Overall, rTMS has been used to target three main consequences of SCI: a) sensory and motor function impairments, b) spasticity, and c) ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT02899637

Effects of Transcranial Magnetic Stimulation in Incomplete ... The main objective is to conduct a study protocol to investigate the effects of repetitive Transcranial Magnetic Stimulation (rTMS) on sensory and motor ...

5. frontiersin.org frontiersin.org/journals/neurology/articles/10.3389/fneur.2025.1587060/full

Repetitive transcranial magnetic stimulation for enhancing ... This narrative review examines the current state of evidence regarding the therapeutic use of rTMS for motor function recovery after SCI.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11766194

Repetitive Transcranial Magnetic Stimulation for the Treatment ... This review is expected to offer a relatively comprehensive understanding and new perspectives of rTMS for SCI treatment. Keywords: spinal cord injury, ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9094636/

Safety and recommendations for TMS use in healthy subjects ... Safety and recommendations for TMS use in healthy subjects and patient populations, with updates on training, ethical and regulatory issues: Expert Guidelines

8. clinicaltrial.be clinicaltrial.be/en/details/14573?per_page=100&recruiting=1&enrolling_by_invitation=0&active_not_recruiting=0&not_yet_recruiting=0&completed=0&only_recruiting=1&only_eligible=0

Dosing rTMS for Depression Post-SCI Repetitive transcranial magnetic stimulation (rTMS), a type of non-invasive brain stimulation, is an FDA-approved treatment option for major ...