Spinal Stimulation for Depression
(MOSPID Trial)
Recruiting in Palo Alto (17 mi)
Overseen ByFrancisco Romo-Nava, MD, PhD
Age: 18 - 65
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Academic
Recruiting
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
Trial Summary
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.
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.
12345Is 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.
16789How 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.
110111213Eligibility 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
+7 more
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
+15 more
Trial 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
Participant Groups
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.
4Treatment groups
Active Control
Placebo Group
Group I: 3.5 ActiveActive Control1 Intervention
Group II: 3.0 ActiveActive Control1 Intervention
Group III: 2.5 ActiveActive Control1 Intervention
Group IV: 2.0 ShamPlacebo Group1 Intervention
Sham will also be compared to "No intervention"
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Lindner Center of HopeMason, OH
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Who Is Running the Clinical Trial?
University of CincinnatiLead Sponsor
National Institute of Mental Health (NIMH)Collaborator
References
Spinal Direct Current Stimulation Modulates Short Intracortical Inhibition. [2022]Transcutaneous spinal direct current stimulation (tsDCS) is a new and safe technique for modulating spinal cord excitability. We assessed changes in intracortical excitability following tsDCS by evaluating changes in cortical silent period (cSP), paired-pulse short intracortical inhibition (SICI), and intracortical facilitation (ICF).
Modulation of soleus H reflex by spinal DC stimulation in humans. [2022]Transcranial direct current stimulation (tDCS) of the human motor cortex induces changes in excitability within cortical and spinal circuits that occur during and after the stimulation. Recently, transcutaneous spinal direct current stimulation (tsDCS) has been shown to modulate spinal conduction properties, as assessed by somatosensory-evoked potentials, and transynaptic properties of the spinal neurons, as tested by postactivation depression of the H reflex or by the RIII nociceptive component of the flexion reflex in the lower limb. To further explore tsDCS-induced plastic changes in spinal excitability, we examined, in a double-blind crossover randomized study, the stimulus-response curves of the soleus H reflex before, during, at current offset and 15 min after anodal, cathodal, and sham tsDCS delivered at the Th11 level (2.5 mA, 15 min, 0.071 mA/cm(2), 0.064 C/cm(2)) in 17 healthy subjects. Anodal tsDCS induced a progressive leftward shift of the recruitment curve of the soleus H reflex during the stimulation; the effects persisted for at least 15 min after current offset. In contrast, both cathodal and sham tsDCS had no significant effects. This exploratory study provides further evidence for the use of tsDCS as an expedient, noninvasive tool to induce long-lasting plastic changes in spinal circuitry. Increased spinal excitability after anodal tsDCS may have potential for spinal neuromodulation in patients with central nervous system lesions.
Effectiveness of transcranial direct current stimulation preceding cognitive behavioural management for chronic low back pain: sham controlled double blinded randomised controlled trial. [2023]To evaluate the effectiveness of transcranial direct current stimulation alone and in combination with cognitive behavioural management in patients with non-specific chronic low back pain.
Transcutaneous spinal direct current stimulation. [2022]In the past 10 years renewed interest has centered on non-invasive transcutaneous weak direct currents applied over the scalp to modulate cortical excitability ("brain polarization" or transcranial direct current stimulation, tDCS). Extensive literature shows that tDCS induces marked changes in cortical excitability that outlast stimulation. Aiming at developing a new, non-invasive, approach to spinal cord neuromodulation we assessed the after-effects of thoracic transcutaneous spinal DC stimulation (tsDCS) on somatosensory potentials (SEPs) evoked in healthy subjects by posterior tibial nerve (PTN) stimulation. Our findings showed that thoracic anodal tsDCS depresses the cervico-medullary PTN-SEP component (P30) without eliciting adverse effects. tsDCS also modulates post-activation H-reflex dynamics. Later works further confirmed that transcutaneous electric fields modulate spinal cord function. Subsequent studies in our laboratory showed that tsDCS modulates the flexion reflex in the human lower limb. Besides influencing the laser evoked potentials (LEPs), tsDCS increases pain tolerance in healthy subjects. Hence, though the underlying mechanisms remain speculative, tsDCS modulates activity in lemniscal, spinothalamic, and segmental motor systems. Here we review currently available experimental evidence that non-invasive spinal cord stimulation (SCS) influences spinal function in humans and argue that, by focally modulating spinal excitability, tsDCS could provide a novel therapeutic tool complementary to drugs and invasive SCS in managing various pathologic conditions, including pain.
The effect of transcutaneous spinal direct current stimulation on corticospinal excitability in chronic incomplete spinal cord injury. [2018]This study investigated the feasibility of modulating bilateral corticospinal excitability with different polarities of transcutaneous spinal direct current stimulation (tsDCS) in chronic, incomplete spinal cord injury (SCI).
Modeling Trans-Spinal Direct Current Stimulation in the Presence of Spinal Implants. [2020]Trans-spinal direct current stimulation (tsDCS) is a technique considered for the treatment of corticospinal damage or dysfunction. TsDCS aims to induce functional modulation in the corticospinal circuitry via a direct current (DC) generated an electric field (EF). To ensure subject safety, subjects with metallic implants are generally excluded from receiving neural dc stimulation. However, spinal injuries often require spinal implants for stabilization. Our goal was to investigate implant imposed changes to EF and current density (CD) magnitude during tsDCS. We simulated the EF and CD, generated by tsDCS in the presence of spinal rods for two electrode configurations and four implant locations along the spinal cord. For each scenario, a no-implant condition was computed for comparison. We assessed changes in EF and CD at the implant location and the EF inside the spinal cord. Our results show that implant presence was able to influence peak CD, compared to the no-implant condition. Nonetheless, the highest calculated CD levels were a factor six lower than those thought to lead to hazardous tissue-damaging effects. Additionally, implant presence did not considerably affect the average EF inside the spinal cord. Our findings do therefore not indicate potentially unsafe CD levels, or significant alterations to stimulation intensity inside the spinal cord, caused by a spinal implant during tsDCS. Our results are relevant to the safety of transcutaneous spinal stimulation applied in the presence of metallic spinal implants.
Spinal DC stimulation in humans modulates post-activation depression of the H-reflex depending on current polarity. [2022]Transcranial direct current stimulation induces long-lasting changes in cortical excitability in humans depending on the current used. Further, transcutaneous spinal application of direct current (tsDCS) induces plastic changes in spinal conduction properties, tested by somatosensory evoked potentials. To verify this thesis on plastic changes in spinal circuitry, we investigated the effects of tsDCS on H-reflex size and post-activation depression.
Safety of Transcranial Direct Current Stimulation: Evidence Based Update 2016. [2022]This review updates and consolidates evidence on the safety of transcranial Direct Current Stimulation (tDCS). Safety is here operationally defined by, and limited to, the absence of evidence for a Serious Adverse Effect, the criteria for which are rigorously defined. This review adopts an evidence-based approach, based on an aggregation of experience from human trials, taking care not to confuse speculation on potential hazards or lack of data to refute such speculation with evidence for risk. Safety data from animal tests for tissue damage are reviewed with systematic consideration of translation to humans. Arbitrary safety considerations are avoided. Computational models are used to relate dose to brain exposure in humans and animals. We review relevant dose-response curves and dose metrics (e.g. current, duration, current density, charge, charge density) for meaningful safety standards. Special consideration is given to theoretically vulnerable populations including children and the elderly, subjects with mood disorders, epilepsy, stroke, implants, and home users. Evidence from relevant animal models indicates that brain injury by Direct Current Stimulation (DCS) occurs at predicted brain current densities (6.3-13 A/m(2)) that are over an order of magnitude above those produced by conventional tDCS. To date, the use of conventional tDCS protocols in human trials (≤40 min, ≤4 milliamperes, ≤7.2 Coulombs) has not produced any reports of a Serious Adverse Effect or irreversible injury across over 33,200 sessions and 1000 subjects with repeated sessions. This includes a wide variety of subjects, including persons from potentially vulnerable populations.
Trans-Spinal Direct Current Stimulation in Neurological Disorders: A systematic review. [2023]Trans-spinal direct current stimulation (tsDCS) is a noninvasive stimulation technique that applies direct current stimulation over spinal levels. However, the effectiveness and feasibility of this stimulation are still unclear. This systematic review summarizes the effectiveness of tsDCS in clinical and neurophysiological outcomes in neurological patients, as well as its feasibility and safety.
Trans-spinal direct current stimulation modifies spinal cord excitability through synaptic and axonal mechanisms. [2021]The spinal cord is extremely complex. Therefore, trans-spinal direct current stimulation (tsDCS) is expected to produce a multitude of neurophysiological changes. Here, we asked how tsDCS differentially affects synaptic and nonsynaptic transmission. We investigated the effects of tsDCS on synaptically mediated responses by stimulating the medullary longitudinal fascicle and recording responses in the sciatic nerve and triceps and tibialis anterior muscles. Response amplitude was increased during cathodal-tsDCS (c-tsDCS), but reduced during anodal-tsDCS (a-tsDCS). After-effects were dependent on the frequency of the test stimulation. c-tsDCS-reduced responses evoked by low-frequency (0.5 Hz) test stimulation and increased responses evoked by high-frequency (400 Hz) test stimulation. a-tsDCS had opposite effects. During and after c-tsDCS, excitability of the lateral funiculus tract (LFT) and dorsal root fibers was increased. However, a-tsDCS caused a complex response, reducing the excitability of LFT and increasing dorsal root fiber responses. Local DC application on the sciatic nerve showed that the effects of DC on axonal excitability were dependent on polarity, duration of stimulation, temporal profile (during vs. after stimulation), orientation of the current direction relative to the axon and relative to the direction of action potential propagation, distance from the DC electrode, and the local environment of the nervous tissue. Collectively, these results indicate that synaptic as well as axonal mechanisms might play a role in tsDCS-induced effects. Therefore, this study identified many factors that should be considered in interpreting results of DCS and in designing tsDCS-based interventions.
An unexpected target of spinal direct current stimulation: Interhemispheric connectivity in humans. [2022]Transcutaneous spinal Direct Current Stimulation (tsDCS) is a noninvasive technique based on the application of weak electrical currents over spinal cord.
Modulation of temporal summation threshold of the nociceptive withdrawal reflex by transcutaneous spinal direct current stimulation in humans. [2017]Transcutaneous spinal direct current stimulation (tsDCS) modulates spinal cord pain pathways. The study is aimed to clarify the neurophysiology of the tsDCS-induced modulation of the spinal cord pain processing by evaluating the effect of the tsDCS on temporal summation threshold (TST) of the nociceptive withdrawal reflex (NWR).
Modeling Electric Fields in Transcutaneous Spinal Direct Current Stimulation: A Clinical Perspective. [2023]Clinical findings suggest that transcutaneous spinal direct current stimulation (tsDCS) can modulate ascending sensitive, descending corticospinal, and segmental pathways in the spinal cord (SC). However, several aspects of the stimulation have not been completely understood, and realistic computational models based on MRI are the gold standard to predict the interaction between tsDCS-induced electric fields and anatomy. Here, we review the electric fields distribution in the SC during tsDCS as predicted by MRI-based realistic models, compare such knowledge with clinical findings, and define the role of computational knowledge in optimizing tsDCS protocols. tsDCS-induced electric fields are predicted to be safe and induce both transient and neuroplastic changes. This could support the possibility to explore new clinical applications, such as spinal cord injury. For the most applied protocol (2-3 mA for 20-30 min, active electrode over T10-T12 and the reference on the right shoulder), similar electric field intensities are generated in both ventral and dorsal horns of the SC at the same height. This was confirmed by human studies, in which both motor and sensitive effects were found. Lastly, electric fields are strongly dependent on anatomy and electrodes' placement. Regardless of the montage, inter-individual hotspots of higher values of electric fields were predicted, which could change when the subjects move from a position to another (e.g., from the supine to the lateral position). These characteristics underlines the need for individualized and patient-tailored MRI-based computational models to optimize the stimulation protocol. A detailed modeling approach of the electric field distribution might contribute to optimizing stimulation protocols, tailoring electrodes' configuration, intensities, and duration to the clinical outcome.