Spinal Stimulation for Depression

(MOSPID Trial)

Overseen By Francisco Romo-Nava, MD, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1 & 2

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for major depressive disorder (MDD) using transcutaneous spinal direct current stimulation (tsDCS). The goal is to determine if stimulating specific spinal pathways can improve depression symptoms. Researchers aim to identify the optimal dose and its effects on brain signals associated with depression. Suitable participants have experienced a current episode of MDD for at least four weeks but not more than two years and are on stable antidepressant medication. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to receive this innovative treatment.

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 prior data suggests that this spinal stimulation technique is safe for treating depression?

Research has shown that transcutaneous spinal direct current stimulation (tsDCS) is generally safe. In over 18,000 sessions with both healthy individuals and those with neurological or mental health conditions, no serious health issues occurred. This indicates that participants did not experience major problems from the treatment.

Studies also indicate that tsDCS is well-tolerated. In trials involving individuals with chronic pain, participants managed the treatment without significant issues. These findings suggest that tsDCS is a promising and safe option for exploring new treatments for depression. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for depression?

Researchers are excited about transcutaneous spinal direct current stimulation (tsDCS) for treating depression because it offers a non-invasive approach, unlike traditional treatments like antidepressant medications and psychotherapy. This method involves applying a mild electrical current to the spinal cord, which could modulate neural pathways linked to mood regulation. Unlike medications, which can take weeks to become effective and often have side effects, tsDCS has the potential to provide quicker relief with fewer side effects. Additionally, this technique might benefit patients who haven't responded well to conventional treatments, offering a new avenue of hope for those with treatment-resistant depression.

What evidence suggests that transcutaneous spinal direct current stimulation might be an effective treatment for major depressive disorder?

Research has shown that a new method called transcutaneous spinal direct current stimulation (tsDCS) could help treat major depressive disorder (MDD). A small initial study found that tsDCS is safe, easy to handle, and may assist with MDD. Early results suggest that tsDCS can change how certain brain areas process signals from the body, potentially improving depression symptoms. Other studies indicate that similar types of stimulation can reduce depression symptoms and work well with medications. In this trial, participants will receive different active doses of tsDCS or a sham treatment to evaluate its effectiveness. Overall, tsDCS presents a promising new option for people with MDD. ^{5 6 7 8 9}

Who Is on the Research Team?

Francisco Romo-Nava, MD, PhD

Principal Investigator

Lindner Center of Hope/ University of Cincinnati

Are You a Good Fit for This Trial?

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 can do tasks required by the study.

Using an effective contraceptive method for participants with childbearing potential

Exclusion Criteria

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

Any other relevant clinical reason as judged by the clinician

My IQ is suspected to be below 80.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

Group I: 3.0 Active Active Control 1 Intervention

Group II: 3.5 Active Active Control 1 Intervention

Group III: 2.5 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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12485468/

Effects of Transcranial Direct Current Stimulation on pain and ... tDCS appears to decrease pain intensity and modulate thresholds for pressure and heat pain, as well as enhance tolerance to heat and cold.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8450534/

Effects of Transcutaneous Spinal Direct Current Stimulation ... Our results demonstrated that the use of tsDCS for chronic pain subjects is safe and feasible. All subjects tolerated the stimulation well ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1935861X11001197

Transcranial direct current stimulation in treatment resistant ... Scores on the Hamilton Depression Rating Scale were reduced from baseline by 14.7% for active tDCS and 10% for placebo tDCS. In contrast, subjective mood ...

4. nature.com nature.com/articles/s41380-023-02349-9

Effect of non-invasive spinal cord stimulation in ... The results from this pilot study suggest that tsDCS is feasible, well-tolerated, and shows therapeutic potential in MDD.

5. joghnp.scholasticahq.com joghnp.scholasticahq.com/article/77442-transcranial-direct-current-stimulation-as-an-adjuvant-in-the-improvement-of-symptoms-of-depression-a-quasi-experimental-design-study

Transcranial direct current stimulation as an adjuvant in the ... Transcranial direct current stimulation is an effective therapeutic option in the reduction of depressive symptoms as an adjunct to pharmacological treatment.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5007190/

Safety of transcranial Direct Current Stimulation: Evidence ... To date, the use of conventional tDCS protocols in human trials (≤40 min, ≤4 mA, ≤7.2 Coulombs) has not produced any reports of a Serious Adverse Effect or ...

7. epain.org epain.org/journal/view.html?uid=1917&vmd=Full

Effects of Transcranial Direct Current Stimulation on pain ... Conclusions: Our findings suggest that tDCS might be effective for fibromyalgia, migraine, and neuropathic pain associated with spinal cord ...

8. sciencedirect.com sciencedirect.com/science/article/abs/pii/S138824572400316X

Effects of cervical transcutaneous spinal direct current ... No serious adverse events have been reported so far in over 18,000 sessions administered to healthy participants, neurological and psychiatric patients.

9. frontiersin.org frontiersin.org/journals/neurology/articles/10.3389/fneur.2021.695910/full

Effects of Transcutaneous Spinal Direct Current Stimulation ... Our results demonstrated that the use of tsDCS for chronic pain subjects is safe and feasible. All subjects tolerated the stimulation well ...