Spinal Cord Stimulation for Parkinson's Disease Rehabilitation
ConditionParkinson Disease
Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age18-80
SponsorUniversity of Louisville
About this trial
This study explores the use of multifunctional, non-invasive spinal cord transcutaneous stimulation (scTS) to address axial motor symptoms, particularly gait dysfunction, in Parkinson's disease (PD). These symptoms, resistant to levodopa and inadequately managed by deep brain stimulation (DBS), arise from maladaptive spinal network changes. A non-invasive approach like scTS could overcome limitations associated with invasive spinal cord stimulation (SCS), which requires surgical implantation and lacks adaptability in stimulation site adjustments.
Gait dysfunction in PD stems from disrupted interactions between spinal and supraspinal networks. scTS provides a non-invasive alternative, shown to enhance locomotor functions in conditions such as spinal cord injury, stroke, and cerebral palsy. This study hypothesizes that scTS applied at multiple spinal levels-cervical (C3-C4), thoracic (T11-T12), and lumbar (L1, L2-L3)-can synergistically activate locomotor central pattern generators (CPGs) and improve gait and postural control in PD. Additionally, it is hypothesized that proprioceptive input, combined with scTS, can counteract disruptions in spinal networks and restore voluntary movement.
The primary goal is to evaluate the effects of scTS on stepping performance, postural control, and locomotor recovery in PD. Specific objectives include:
1. Enhancing Locomotor Networks
* Determine optimal scTS parameters for inducing rhythmic stepping in PD patients. * Assess interactions between spinal and supraspinal networks during imagined stepping under scTS in a gravity-neutral setting. 2. Improving Postural Networks
o Evaluate the effectiveness of scTS in restoring postural control and integrating postural-locomotor functions. 3. Facilitating Neuroplasticity for Movement Recovery o Combine scTS with activity-based recovery training to promote adaptive plasticity in spinal and cortical networks, reducing freezing of gait (FOG).
The research will measure scTS's capacity to generate coordinated stepping and postural movements, integrate proprioceptive feedback, and induce long-term improvements in gait parameters. By targeting spinal locomotor and postural systems, scTS offers a novel, non-invasive approach to addressing gaps in the management of PD gait dysfunction. This work has the potential to significantly enhance the quality of life for individuals with PD, providing a safe, adaptable, and patient-centered therapeutic solution.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Diagnosis of Parkinson's disease;
Adults aged 18 to 80 years;
Competent to give informed consent for the research protocol;
Able to understand instructions;
Disqualifiers
Co-morbidities affecting gait;
Clinically significant cognitive dysfunction;
Clinically significant depression or major active psychiatric illness such as schizophrenia, bipolar disorder, or major depressive disorder;
Terminal illness associated with <12-month survival;
Trial design
Design model
Single group
Treatments tested in this trial
Spinal cord transcutaneous stimulation (scTS)
DevicescTS mapping: Each intervention session will be approximately 2 hours each which includes time to place the scTS stimulating pads and other sensors as needed. Participants will be asked to train 3 days per week during the intervention periods so that they achieve at least 12 sessions. In instances in which availability is limited or they must cancel a session, the intervention period will need to be extended slightly (up to a maximum of four weeks) so that they can achieve at least 12 sessions (1-month intervention period) or 24 sessions (2-month intervention periods) of training. The main study interventions are described below. Step-scTS: Step-scTS is spinal cord transcutaneous stimulation (scTS) targeted for stepping function. The scTS mapping assessment(s) will assist the study team in determining optimized stimulation parameters for each body and f
Treatment groups
20 Participants
are divided into 1 treatment groupGroup A: Non-invasive spinal neuromodulation trainingExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
A. Assessment of Multisegmental Motor Responses (MMR)
Multisegmental motor responses in different leg muscles evoked by non-invasive stimulation of the dorsal lumbosacral spinal cord will be recorded. Such responses are the basic components of the lower-limb muscle responses that are elicited by transcutaneous stimulation of posterior lumbar cord structures. Multi-Segmental Motor Responses will be evoked transcutaneously by using a constant current stimulator (Cosyma, Inc. or Digitimer-Constant Current Stimulator, e.g., DS8R) between the C2 spinous process and the Coccyx. Small cathodes (pre-gelled, soft surface electrodes) will be placed over the skin between the C2 spinous process and Coccyx (midline with a single cathode or left and right of midline with a split cathode) while larger anode(s) will be placed over the anterior spine at different levels, at segments just below the cathode, on the abdomen, or along the pelvis.
Time frame
From date of screening until the date of data is analyzed, up to 48 months.2
Spinal Cord Transcutaneous Stimulation (scTS) Mapping electromyography (EMG)
Mapping will be carried out through assessment of electrophysiological and functional changes. EMG will be used to assess muscle activity. The mapping assessment may take place with the participant in supine, side-lying in a gravity-neutral device, upright while standing, or upright while stepping. Assistance will be provided as needed. A safety limit of 250 mA will be implemented. Other stimulation parameters include: 5-10 kHz carrier frequency for modulation of discomfort from stimulation, 0.25-3.0 ms pulse width duration, and 10-100 Hz.
Time frame
From date of screening until the date of data is analyzed, up to 48 months.3
Spinal Cord Transcutaneous Stimulation (scTS) Mapping electroencephalography (EEG)
Mapping will be carried out through assessment of electrophysiological and functional changes. EEG will be used to assess brain activity. The mapping assessment may take place with the participant in supine, side-lying in a gravity-neutral device, upright while standing, or upright while stepping. Assistance will be provided as needed. A safety limit of 250 mA will be implemented. Other stimulation parameters include: 5-10 kHz carrier frequency for modulation of discomfort from stimulation, 0.25-3.0 ms pulse width duration, and 10-100 Hz.
Time frame
From date of screening until the date of data is analyzed, up to 48 months.4
Stepping Performance in a Gravity-Neutral Device (GND) with electromyography (EMG).
Limb coordination and muscle activation during visual imaginary stepping and gravity-neutral ambulation will be assessed with surface EMG of multiple trunk and lower extremity muscles including pelvic stabilizers (quadratus lumborum), hip extensors (gluteus), hip flexors (iliopsoas), knee extensor (rectus femoris), knee flexor (biceps femoris), ankle dorsiflexor (tibialis anterior), and ankle plantar flexor (medial gastrocnemius and soleus) without and with scTS.
Time frame
From date of screening until the date of data is analyzed, up to 48 months.Secondary outcomes
1
Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS)
The Movement Disorder Society (MDS)-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Task Force revised and expanded the UPDRS. It has four parts: I: Non-motor Experiences of Daily Living; II: Motor Experiences of Daily Living; III: Motor Examination; IV: Motor Complications. Twenty questions are completed by the participant. The Non-motor Experiences of Daily Living (part I) include questions on cognitive impairment, hallucinations and psychosis, depressed mood, anxious mood, apathy, dopamine dysregulation syndrome, sleep, pain and other sensations, urinary problems, constipation problems, orthostatic hypotension, and fatigue. Motor Experiences of Daily Living (part II) include questions related to speech, saliva and drooling, chewing and swallowing, eating tasks, dressing, hygiene, handwriting, participating in hobbies and other activities, turning in bed, tremor, getting out of bed, walking and balance, and freezing.
Time frame
From date of screening until the date of data is analyzed, up to 48 months.2
Time to Navigate (TTN) Test
The Time to Navigate (TTN) test was developed as a practical and objective clinical measure of FOG severity. The TTN test involves similar situations as those in the Rating Instrument to Assess Festination and Freezing of Gait with single-tasking and dual-tasking. The TTN does not include navigating through a door but instead includes a longer walking pass and navigating around an object and a narrow corridor. Completing both assessments with participants who opt into participating will allow comparison between the two clinical measures and additional information about participants' functional presentation and what kinds of activities elicit FOG.
Time frame
From date of screening until the date of data is analyzed, up to 48 months.3
Modified Ashworth Scale (MAS) and Range of Motion (ROM) Testing
The modified Ashworth Scale scores muscle spasticity by assessing the resistance observed during passive muscle stretching. A six-category ordinal scale (0 = no increase in muscle tone; 1 = Slight increase in muscle tone with catch and release; 1+ = Slight increase in tone with catch; 2 = Marked increase in muscle tone but affected parts move easily; 3 = considerable increase in muscle tone and passive movement is difficult; 4 = affected part(s) rigid in flexion or extension) is used to score the participant's spasticity in the muscles of interest. During the MAS, range of motion (ROM) testing will also be completed to track any musculoskeletal abnormalities and/or improvements in ROM. sEMG, fine wire EMG, joint kinematics, and body weight force will be measured.
Time frame
From date of screening until the date of data is analyzed, up to 48 months.4
10-Meter Walk Test
The 10-meter walk test (10MWT) assesses walking speed in meters per second over a short duration. Assistive devices can be used during this test. Participants will be given space to accelerate to their preferred walking speed before the start of the 10-meter distance. sEMG, fine wire EMG, joint kinematics, and body weight force will be measured. Following an initial 10MWT without stimulation and adequate rest, participants who are able will repeat the test with multi-site scTS.
Time frame
From date of screening until the date of data is analyzed, up to 48 months.Other outcomes
1
Propriospinal Pathway Assessment (PSPA)
Propriospinal pathways will be assessed by electrically or magnetically stimulating a variety of peripheral nerves such as, but not limited to, the ulnar, superficial radial, common and superficial peroneal, and femoral nerves. We will then record interlimb reflexes/responses from various muscles at rest. Surface or fine-wire electrodes to record this activity will be utilized. Additionally, nerve stimulation could be paired with various other types of stimulation, which could be the Hoffman reflex, multisegmental motor responses (MMRs), or in the presence of transcutaneous electrical stimulation. Conditioning of these responses will allow us to identify the effects of propriospinal pathways in the human spinal cord under conditions when we typically might not be able to see these responses in resting muscles.
Time frame
From date of screening until the date of data is analyzed, up to 48 months.2
Supraspinal Connectivity Assessment (SSCA)
Test responses will be evoked using sub maximal transcutaneous electrical spinal cord stimulation of 1 ms duration at intensities of up to 100 mA delivered over the intra-spinous space between the spinous processes of the T10 and Coccyx vertebrae, with participants lying in a supine position. Stimulation will be delivered using Digitimer constant current stimulator (Digitimer Ltd., UK). Reponses will be recorded via surface EMG electrodes placed bilaterally over the proximal and distal lower extremities' muscles. The conditioning stimulation will precede the test pulse to assess the Long propriospinal pathways: Electrical stimulus over the lateral epicondyle as well as between the intra-spinous space between C3 and C5 or ulnar nerve stimulation using a Digitimer constant current stimulator (Digitimer Ltd., UK). The intervals between the conditioning and test stimuli will vary from 5 to 200 ms.
Time frame
From date of screening until the date of data is analyzed, up to 48 months.3
Reticulospinal Pathway Assessment (RSPA)
The reticulospinal pathway has been attributed to widespread muscle contractions in response to sudden unexpected auditory stimuli. The latency, habituation after repeated stimuli and characteristics of muscular contraction suggest that the most likely mediating structure is the reticular formation in the medulla and pons. Implementing an acoustic startle reaction has been shown to result in muscles responses in facial, arm and sometimes leg muscles that are attributed to the reticulospinal pathways. After SCI it appears that the reticulospinal pathway is strengthened as a compensatory mechanism. The reticulospinal pathway will be evaluated either while the participant is at rest or through paired conditioning studies.
Time frame
From date of screening until the date of data is analyzed, up to 48 months.4
Voluntary Motor Control of Hip, Knee, Ankle, and Toe Assessment
This novel assessment paradigm was developed to evaluate the state of the corticospinal pathway by using stimulation pulses timed with a task-driven movement attempt. Force levels will be assessed with a force transducer secured to a cable and/or a dynamometer that is attached to the appropriate limb segment and the associated muscle activity patterns will be assessed from surface EMG recordings of the appropriate muscles: hip extensor (gluteus), hip flexor (iliopsoas), knee extensor (rectus femoris), knee flexor (biceps femoris), ankle dorsiflexor (tibialis anterior), and ankle plantar flexors (medial gastrocnemius and soleus). Participants will be lying supine on a bed, supine or seated on an adjustable reclining chair with their leg strapped to a dynamometer to measure force, or side-lying in the GND. Spinal stimulation will be provided over the thoracolumbosacral spinal cord (e.g., between L1-L2 vertebral bodies).
Time frame
From date of screening until the date of data is analyzed, up to 48 months.Sponsors and contacts
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Source ClinicalTrials.gov