Spinal Stimulation for Depression

(MOSPID Trial)

Overseen By Francisco Romo-Nava, MD, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: University of Cincinnati

Must be taking: Antidepressants

Must not be taking: Anticonvulsants, Calcium channel blockers

Disqualifiers: Bipolar, Schizophrenia, Substance use, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 5 weeks

67 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires participants to be on a stable dose of an FDA-approved antidepressant for at least 8 weeks before joining. However, you cannot participate if you are using anticonvulsant medications, calcium channel blockers, or need chronic pain medication like NSAIDs and opiates.

What data supports the effectiveness of the treatment Transcutaneous Spinal Direct Current Stimulation for depression?

Research shows that Transcutaneous Spinal Direct Current Stimulation (tsDCS) can modulate spinal cord function and increase pain tolerance, suggesting it might help manage various conditions. While not directly studied for depression, its ability to influence spinal and brain activity could potentially offer therapeutic benefits. ^{1 2 3 4 5}

Is transcutaneous spinal direct current stimulation (tsDCS) safe for humans?

Research indicates that transcutaneous spinal direct current stimulation (tsDCS) is generally safe for humans, even in the presence of spinal implants, as it does not reach levels that could damage tissue. Studies have not reported any serious adverse effects or irreversible injuries from tsDCS in human trials. ^{1 6 7 8 9}

How does the treatment Transcutaneous Spinal Direct Current Stimulation (tsDCS) for depression differ from other treatments?

Transcutaneous Spinal Direct Current Stimulation (tsDCS) is unique because it uses weak electrical currents applied over the spinal cord to modulate its excitability, potentially affecting both pain pathways and interhemispheric brain connectivity. Unlike traditional depression treatments like medication or psychotherapy, tsDCS is noninvasive and targets the spinal cord directly, which may lead to different neurophysiological changes. ^{1 10 11 12 13}

What is the purpose of this trial?

Spinal interoceptive pathways (SIPs) convey bodily signals to an interoceptive system in the brain and their dysregulation is linked to major depressive disorder (MDD). Current treatments are partially effective and the role of SIPs in MDD is vastly unexplored. Preliminary data suggests that SIPs are feasible therapeutic targets in MDD. The central hypothesis is that non-invasive spinal cord stimulation will modulate SIPs to elucidate their role and therapeutic potential in MDD using an R61/33 phased innovation approach. R61 phase specific aims (SA). The specific goal will be to evaluate spinal and brain-based SIPs target engagement markers of transcutaneous spinal direct current stimulation (tsDCS) in MDD with two SAs: SA1) To determine tsDCS SIPs modulation using laser-evoked potentials (LEPs) as electroencephalography (EEG)- based neural measures of target engagement. SA2) To evaluate optimal tsDCS dose based upon tolerability and SIPs target engagement markers. Anodal tsDCS will be evaluated as a tool to modulate SIPs in MDD. SIPs (Aδ and C fibers) can be evaluated via LEPs as neural measures (EEG) elicited in MDD-relevant brain regions within an interoceptive system. Prior data shows anodal tsDCS inhibits SIPs and LEPs N2 component will be assessed as tsDCS engagement markers. Adults with MDD (n=67) will participate in a double-blind, crossover, sham-controlled study to evaluate tsDCS at 0,2.5,3, and 3.5 mA. The working hypothesis is that tsDCS will induce a change in LEPs (SA1) in a dose-dependent and tolerable manner (SA2), supporting their use as SIPs engagement markers. Go/No-Go milestones: Compared to sham, the active tsDCS dose that induces a change in LEPs at a preestablished threshold will be evidence of SIPs engagement and "Go" criteria for the R33 phase.

Research Team

Francisco Romo-Nava, MD, PhD

Principal Investigator

Lindner Center of Hope/ University of Cincinnati

Eligibility Criteria

This trial is for adults with Major Depressive Disorder (MDD) who may benefit from a non-invasive treatment. Participants should be interested in exploring new therapeutic options that involve spinal cord stimulation to manage their depression symptoms.

Inclusion Criteria

My mental health treatment has been stable for over 4 weeks.

I have anxiety, but it's moderate and not my primary health issue.

Using an effective contraceptive method for participants with childbearing potential

Exclusion Criteria

My blood pressure is stable and not above 150/95 mmHg.

My IQ is suspected to be below 80.

Any other relevant clinical reason as judged by the clinician

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive transcutaneous spinal direct current stimulation (tsDCS) to evaluate spinal and brain-based SIPs target engagement markers in MDD

5 weeks

Multiple visits for tsDCS sessions and assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Transcutaneous Spinal Direct Current Stimulation

Trial Overview The study tests if transcutaneous spinal direct current stimulation (tsDCS) can modulate bodily signals linked to MDD. It's a double-blind, crossover, sham-controlled study where participants receive different doses of tsDCS to see how it affects brain activity related to depression.

Participant Groups

Group I: 2.5 Active Active Control 1 Intervention

Group II: 3.5 Active Active Control 1 Intervention

Group III: 3.0 Active Active Control 1 Intervention

Group IV: 2.0 Sham Placebo Group 1 Intervention

Sham will also be compared to "No intervention"

Who Is Running the Clinical Trial?

University of Cincinnati

Lead Sponsor

Trials

442

Recruited

639,000+

National Institute of Mental Health (NIMH)

Collaborator

Trials

3,007

Recruited

2,852,000+

Findings from Research

Transcutaneous spinal direct current stimulation (tsDCS) is a safe technique that can effectively modulate spinal cord excitability, as shown by changes in motor-evoked potentials (MEPs) in healthy subjects after stimulation.

The study found that cathodal tsDCS increased MEP amplitudes indicating enhanced inhibitory GABA(A)ergic drive, while anodal tsDCS had the opposite effect, suggesting tsDCS could be a promising rehabilitation strategy for patients with acute brain lesions or spinal diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Spinal Direct Current Stimulation Modulates Short Intracortical Inhibition. Bocci, T., Barloscio, D., Vergari, M., et al.[2022]

Anodal transcutaneous spinal direct current stimulation (tsDCS) significantly increased spinal excitability, as shown by a leftward shift in the H reflex recruitment curve during and after stimulation in a study of 17 healthy subjects.

Unlike anodal tsDCS, cathodal and sham stimulation did not produce significant effects, suggesting that anodal tsDCS could be a promising noninvasive method for inducing long-lasting changes in spinal circuitry, potentially benefiting patients with central nervous system lesions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modulation of soleus H reflex by spinal DC stimulation in humans. Lamy, JC., Ho, C., Badel, A., et al.[2022]

In a randomized controlled trial involving 135 participants with chronic low back pain, transcranial direct current stimulation (tDCS) was found to be ineffective in reducing pain and disability compared to a sham treatment, with no significant differences in outcomes.

Despite the lack of efficacy, tDCS was well tolerated by participants, showing only minimal and temporary side effects, indicating it is safe for use in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of transcranial direct current stimulation preceding cognitive behavioural management for chronic low back pain: sham controlled double blinded randomised controlled trial. Luedtke, K., Rushton, A., Wright, C., et al.[2023]

Transcutaneous spinal DC stimulation (tsDCS) can effectively modulate spinal cord function without adverse effects, as demonstrated by its ability to depress specific somatosensory potentials in healthy subjects.

tsDCS shows promise as a non-invasive therapeutic tool for managing conditions like pain by influencing spinal excitability, potentially serving as a complementary approach to traditional drugs and invasive spinal cord stimulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcutaneous spinal direct current stimulation. Cogiamanian, F., Ardolino, G., Vergari, M., et al.[2022]

Transcutaneous spinal direct current stimulation (tsDCS) can modulate corticospinal excitability in individuals with chronic incomplete spinal cord injury, showing trends of increased excitability on one side and decreased on the other, depending on the stimulation polarity.

In a study with six participants, no significant differences were found between stimulation conditions, but the results suggest that further research is needed to optimize electrode placement and explore the potential for improved movement function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of transcutaneous spinal direct current stimulation on corticospinal excitability in chronic incomplete spinal cord injury. Powell, ES., Carrico, C., Salyers, E., et al.[2018]

Trans-spinal direct current stimulation (tsDCS) can be safely applied in patients with spinal implants, as the presence of these implants does not significantly increase the risk of hazardous current density levels during stimulation.

The study found that while spinal implants can influence peak current density, the levels remain well below those that could cause tissue damage, ensuring that tsDCS remains a viable treatment option for individuals with spinal injuries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modeling Trans-Spinal Direct Current Stimulation in the Presence of Spinal Implants. Kuck, A., Stegeman, DF., van Asseldonk, EHF.[2020]

Transcutaneous spinal direct current stimulation (tsDCS) can induce lasting changes in spinal circuitry, as shown by its effects on H-reflex post-activation depression in a study of 10 healthy subjects.

Anodal tsDCS decreased H-reflex post-activation depression, while cathodal tsDCS increased it, demonstrating that tsDCS is a non-invasive method to modulate spinal motor pathways effectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Spinal DC stimulation in humans modulates post-activation depression of the H-reflex depending on current polarity. Winkler, T., Hering, P., Straube, A.[2022]

Transcranial Direct Current Stimulation (tDCS) has been shown to be safe, with no reports of Serious Adverse Effects or irreversible injuries across over 33,200 sessions involving more than 1,000 subjects, including vulnerable populations.

Safety assessments indicate that the current densities used in conventional tDCS (≤4 milliamperes) are significantly lower than those that could potentially cause brain injury, suggesting that tDCS protocols are well within safe limits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of Transcranial Direct Current Stimulation: Evidence Based Update 2016. Bikson, M., Grossman, P., Thomas, C., et al.[2022]

Trans-spinal direct current stimulation (tsDCS) has shown potential benefits, such as reducing hypertonia and neuropathic pain, particularly with anodal stimulation in patients with central nervous system diseases, based on a review of 8 studies involving 143 subjects.

The application of tsDCS was found to be feasible and safe, with no severe adverse effects reported, although the overall effectiveness remains uncertain due to variability in study results and the need for further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trans-Spinal Direct Current Stimulation in Neurological Disorders: A systematic review. Fernández-Pérez, JJ., Serrano-Muñoz, D., Beltran-Alacreu, H., et al.[2023]

Trans-spinal direct current stimulation (tsDCS) can significantly alter synaptic and nonsynaptic transmission in the spinal cord, with cathodal stimulation (c-tsDCS) increasing response amplitudes at high frequencies while reducing them at low frequencies, and anodal stimulation (a-tsDCS) having the opposite effects.

The study highlights that the effects of tsDCS on axonal excitability are influenced by various factors, including the polarity of stimulation, duration, and local tissue environment, suggesting that both synaptic and axonal mechanisms contribute to the outcomes of tsDCS interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trans-spinal direct current stimulation modifies spinal cord excitability through synaptic and axonal mechanisms. Ahmed, Z.[2021]

Transcutaneous spinal Direct Current Stimulation (tsDCS) can effectively modulate interhemispheric motor connectivity, with anodal stimulation increasing interhemispheric delay and decreasing the duration of the ipsilateral Silent Period, indicating enhanced communication between brain hemispheres.

The study suggests that tsDCS could serve as a promising therapeutic tool for conditions involving impaired interhemispheric balance, offering a safe alternative for rehabilitation in patients with acute brain lesions when other non-invasive brain stimulation techniques may not be suitable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An unexpected target of spinal direct current stimulation: Interhemispheric connectivity in humans. Bocci, T., Caleo, M., Vannini, B., et al.[2022]

Anodal transcutaneous spinal direct current stimulation (tsDCS) significantly increased the temporal summation threshold of the nociceptive withdrawal reflex in 10 healthy subjects, indicating its potential to modulate spinal cord pain pathways.

This stimulation also led to a decrease in the perception of pain, suggesting that anodal tsDCS could be an effective non-invasive treatment for clinical pain conditions related to spinal cord activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modulation of temporal summation threshold of the nociceptive withdrawal reflex by transcutaneous spinal direct current stimulation in humans. Perrotta, A., Bolla, M., Anastasio, MG., et al.[2017]

Transcutaneous spinal direct current stimulation (tsDCS) is predicted to be safe and can induce both transient and neuroplastic changes in the spinal cord, suggesting potential for new clinical applications, such as in spinal cord injury treatment.

The effectiveness of tsDCS is highly dependent on individual anatomy and electrode placement, highlighting the importance of using MRI-based computational models to tailor stimulation protocols for optimal clinical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modeling Electric Fields in Transcutaneous Spinal Direct Current Stimulation: A Clinical Perspective. Guidetti, M., Giannoni-Luza, S., Bocci, T., et al.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

Spinal Direct Current Stimulation Modulates Short Intracortical Inhibition. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Modulation of soleus H reflex by spinal DC stimulation in humans. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Effectiveness of transcranial direct current stimulation preceding cognitive behavioural management for chronic low back pain: sham controlled double blinded randomised controlled trial. [2023]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Transcutaneous spinal direct current stimulation. [2022]

5. Netherlands pubmed.ncbi.nlm.nih.gov

The effect of transcutaneous spinal direct current stimulation on corticospinal excitability in chronic incomplete spinal cord injury. [2018]

6. United States pubmed.ncbi.nlm.nih.gov

Modeling Trans-Spinal Direct Current Stimulation in the Presence of Spinal Implants. [2020]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Spinal DC stimulation in humans modulates post-activation depression of the H-reflex depending on current polarity. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Safety of Transcranial Direct Current Stimulation: Evidence Based Update 2016. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Trans-Spinal Direct Current Stimulation in Neurological Disorders: A systematic review. [2023]

10. United States pubmed.ncbi.nlm.nih.gov

Trans-spinal direct current stimulation modifies spinal cord excitability through synaptic and axonal mechanisms. [2021]

11. Netherlands pubmed.ncbi.nlm.nih.gov

An unexpected target of spinal direct current stimulation: Interhemispheric connectivity in humans. [2022]

12. Netherlands pubmed.ncbi.nlm.nih.gov

Modulation of temporal summation threshold of the nociceptive withdrawal reflex by transcutaneous spinal direct current stimulation in humans. [2017]

13. Switzerland pubmed.ncbi.nlm.nih.gov

Modeling Electric Fields in Transcutaneous Spinal Direct Current Stimulation: A Clinical Perspective. [2023]