Spinal Cord Injuries Clinical Trial
— STIMO-PHARMAOfficial title:
Acute Effects of Pharmacological Neuromodulation on Leg Motor Activity in Patients With Spinal Cord Injury Treated With Epidural Electrical Stimulation
Verified date | October 2023 |
Source | Centre Hospitalier Universitaire Vaudois |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
In a current first-in-man study, called Stimulation Movement Overground (STIMO) (NCT02936453; CER-VD: 04-2014; Swissmedic: 2016-MD-0002), epidural electrical stimulation (EES) of the spinal cord is applied to enable individuals with severe spinal cord injury (SCI) to complete intensive locomotor neurorehabilitation training. In this clinical feasibility study, it was demonstrated that EES results in an immediate enhancement of locomotor functions and that when applied repeatedly as part of a neurorehabilitation program, EES can progressively improve leg motor control in individuals with severe SCI. Mechanistically, EES acts trans-synaptically upon spinal circuitries through the electrical stimulation of proprioceptive fibers. It is assumed that this stimulation does not increase the level of availability of monoamine neurotransmitters below the SCI level, which are essential for lower extremity movement generation. Specifically, in a non-injured individual, dopamine and serotonin synthesized in the brain and brainstem are released by fibers diffusely innervating the spinal cord, serving to critically mediate excitability of motor neurons and interneurons in lumbar and sacral spinal level. Spinal cord injury would partially or entirely disrupt these modulation pathways, resulting in a detrimental lack of crucial neurotransmitters below the injury level. This lack of endogenous neurotransmitters could potentially be compensated for by pharmacological agents promoting the neurochemical environment necessary for locomotion.
Status | Completed |
Enrollment | 3 |
Est. completion date | October 4, 2023 |
Est. primary completion date | October 4, 2023 |
Accepts healthy volunteers | Accepts Healthy Volunteers |
Gender | All |
Age group | 18 Years to 65 Years |
Eligibility | Inclusion Criteria: - Completed the main phase of the STIMO study - Enrolled in the STIMO study extension - Age 18-65 (women or men) - Sensorimotor or motor complete and incomplete SCI graded as AIS A, B, C & D - Stable medical, physical and psychological condition as considered by Investigators - Able to understand and interact with the study team in French or English - Adequate caregiver support and access to appropriate medical care in the patient's home community - Agree to comply with all conditions of the study and to attend all required study training and visit - Must provide and sign Informed Consent prior to any study-related procedures Exclusion Criteria: - Epilepsy - Women who are pregnant (pregnancy test obligatory for women of childbearing potential) or breastfeeding or not willing to take contraception. - Known or suspected non-compliance, drug or alcohol abuse. - Gastrointestinal ulcers in the last five years - Known or suspected eye disorders or diseases - Known or suspected allergies or hypersensitivity to buspirone, levodopa or carbidopa. - Taking selective and non-selective serotonin reuptake inhibitors or any other treatments acting upon serotonergic transmission, such as the following: - Selective serotonin reuptake inhibitors (SSRIs) - Serotonin-norepinephrine reuptake inhibitors (SNRIs) - Serotonin antagonists and reuptake inhibitors (SARIs) - Tricyclic antidepressants (TCAs) - Tetracyclic antidepressants (TeCAs) - Norepinephrine-dopamine reuptake inhibitors (NDRIs) - Monoamine oxidase inhibitors (MAOIs) - Patients who are receiving treatments altering the noradrenergic and dopaminergic transmission (e.g., bupropion and levodopa/carbidopa) - Patients who are taking narcotic pain killers (e.g., opioids) and neuropathic medication (e.g., gabapentin, pregabalin) - Patients who are taking antihypertensive drugs and diuretics (e.g., furosemide or hydrochlorothiazide) - Patients who are taking hypnotic drugs (e.g., Zolpidem). - Patients receiving D2 antagonists or antipsychotic drugs (e.g., butyrophenone, phenothiazines, risperidone) - Other clinically significant concomitant disease states (e.g., renal failure, hepatic dysfunction, cardiovascular disease, etc.) |
Country | Name | City | State |
---|---|---|---|
Switzerland | CHUV | Lausanne | Vaud |
Lead Sponsor | Collaborator |
---|---|
Centre Hospitalier Universitaire Vaudois | Ecole Polytechnique Fédérale de Lausanne |
Switzerland,
Formento E, Minassian K, Wagner F, Mignardot JB, Le Goff-Mignardot CG, Rowald A, Bloch J, Micera S, Capogrosso M, Courtine G. Electrical spinal cord stimulation must preserve proprioception to enable locomotion in humans with spinal cord injury. Nat Neurosci. 2018 Dec;21(12):1728-1741. doi: 10.1038/s41593-018-0262-6. Epub 2018 Oct 31. — View Citation
Wagner FB, Mignardot JB, Le Goff-Mignardot CG, Demesmaeker R, Komi S, Capogrosso M, Rowald A, Seanez I, Caban M, Pirondini E, Vat M, McCracken LA, Heimgartner R, Fodor I, Watrin A, Seguin P, Paoles E, Van Den Keybus K, Eberle G, Schurch B, Pralong E, Becce F, Prior J, Buse N, Buschman R, Neufeld E, Kuster N, Carda S, von Zitzewitz J, Delattre V, Denison T, Lambert H, Minassian K, Bloch J, Courtine G. Targeted neurotechnology restores walking in humans with spinal cord injury. Nature. 2018 Nov;563(7729):65-71. doi: 10.1038/s41586-018-0649-2. Epub 2018 Oct 31. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Rate of AEs/SAEs/Side effects | Evaluate the safety of oral, single-dose administration of levodopa/carbidopa, buspirone, the combination of buspirone and levodopa/carbidopa, and placebo.
The frequency and the severity AEs and SAEs will be collected thoughout the treatment session Reported side effects throughout the treatment sessions will also be collected by a tailored quantitative/qualitative questionnaire |
Changes from baseline condition over a treatment session of 4 hours | |
Primary | Changes in blood pressure | Evaluate the safety of oral, single-dose administration of levodopa/carbidopa, buspirone, the combination of buspirone and levodopa/carbidopa, and placebo
-Vitals signs will be monitored throughout the treatment session to evaluate the fluctuations from baseline condition. |
Changes from baseline condition over a treatment session of 4 hours | |
Primary | Changes in heart rate | Evaluate the safety of oral, single-dose administration of levodopa/carbidopa, buspirone, the combination of buspirone and levodopa/carbidopa, and placebo
-Vitals signs will be monitored throughout the treatment session to evaluate the fluctuations from baseline condition. |
Changes from baseline condition over a treatment session of 4 hours | |
Secondary | Spasticity of the Lower Extremities (score according to the Pendulum test) | Explore preliminary efficacy of oral, single-dose administration of levodopa/carbidopa, buspirone, the combination of buspirone and levodopa/carbidopa, and placebo.
-Assessment of the lower extremities' spasticity. |
Changes from baseline condition over a treatment session of 4 hours | |
Secondary | Lower Extremity Motor Strength (M0-M5 score according to the AIS) | Explore preliminary efficacy of oral, single-dose administration of levodopa/carbidopa, buspirone, the combination of buspirone and levodopa/carbidopa, and placebo.
-Assessment of the lower extremities' motor strength by a clinician. |
Changes from baseline condition over a treatment session of 4 hours | |
Secondary | Lower Extremity Motor Strength (muscle activity) | Explore preliminary efficacy of oral, single-dose administration of levodopa/carbidopa, buspirone, the combination of buspirone and levodopa/carbidopa, and placebo.
-Assessment of the lower extremities' motor strength by EMGs. |
Changes from baseline condition over a treatment session of 4 hours | |
Secondary | Lower Extremity Voluntary Movements (kinematics assessment through VICON) | Explore preliminary efficacy of oral, single-dose administration of levodopa/carbidopa, buspirone, the combination of buspirone and levodopa/carbidopa, and placebo.
-Participants' voluntary movements will be assessed by kinematics analyses through the VICON) |
Changes from baseline condition over a treatment session of 4 hours | |
Secondary | Lower Extremity Voluntary Movements (muscle activity) | Explore preliminary efficacy of oral, single-dose administration of levodopa/carbidopa, buspirone, the combination of buspirone and levodopa/carbidopa, and placebo.
-Participants' muscles during the voluntary movements will be assessed by EMGs. |
Changes from baseline condition over a treatment session of 4 hours | |
Secondary | Walking speed (10MWT) | Explore preliminary efficacy of oral, single-dose administration of levodopa/carbidopa, buspirone, the combination of buspirone and levodopa/carbidopa, and placebo.
-Participants' velocity will be assessed with a 10MWT with and without EES |
Changes from baseline condition over a treatment session of 4 hours | |
Secondary | Gait pattern (kinematics assessment through VICON) | Explore preliminary efficacy of oral, single-dose administration of levodopa/carbidopa, buspirone, the combination of buspirone and levodopa/carbidopa, and placebo.
-Participants' gait pattern during a 10MWT will be assessed by kinematics analyses through the VICON |
Changes from baseline condition over a treatment session of 4 hours | |
Secondary | Gait pattern (muscle activity) | Explore preliminary efficacy of oral, single-dose administration of levodopa/carbidopa, buspirone, the combination of buspirone and levodopa/carbidopa, and placebo.
-Participants' muscle activity will be assessed during a 10MWT with EMGs. |
Changes from baseline condition over a treatment session of 4 hours |
Status | Clinical Trial | Phase | |
---|---|---|---|
Active, not recruiting |
NCT06321172 -
Muscle and Bone Changes After 6 Months of FES Cycling
|
N/A | |
Completed |
NCT03457714 -
Guided Internet Delivered Cognitive-Behaviour Therapy for Persons With Spinal Cord Injury: A Feasibility Trial
|
||
Recruiting |
NCT05484557 -
Prevention of Thromboembolism Using Apixaban vs Enoxaparin Following Spinal Cord Injury
|
N/A | |
Suspended |
NCT05542238 -
The Effect of Acute Exercise on Cardiac Autonomic, Cerebrovascular, and Cognitive Function in Spinal Cord Injury
|
N/A | |
Recruiting |
NCT05503316 -
The Roll of Balance Confidence in Gait Rehabilitation in Persons With a Lesion of the Central Nervous System
|
N/A | |
Not yet recruiting |
NCT05506657 -
Early Intervention to Promote Return to Work for People With Spinal Cord Injury
|
N/A | |
Recruiting |
NCT04105114 -
Transformation of Paralysis to Stepping
|
Early Phase 1 | |
Recruiting |
NCT03680872 -
Restoring Motor and Sensory Hand Function in Tetraplegia Using a Neural Bypass System
|
N/A | |
Completed |
NCT04221373 -
Exoskeletal-Assisted Walking in SCI Acute Inpatient Rehabilitation
|
N/A | |
Completed |
NCT00116337 -
Spinal Cord Stimulation to Restore Cough
|
N/A | |
Completed |
NCT03898700 -
Coaching for Caregivers of Children With Spinal Cord Injury
|
N/A | |
Recruiting |
NCT04883463 -
Neuromodulation to Improve Respiratory Function in Cervical Spinal Cord Injury
|
N/A | |
Active, not recruiting |
NCT04881565 -
Losing Balance to Prevent Falls After Spinal Cord Injury (RBT+FES)
|
N/A | |
Completed |
NCT04864262 -
Photovoice for Spinal Cord Injury to Prevent Falls
|
N/A | |
Recruiting |
NCT04007380 -
Psychosocial, Cognitive, and Behavioral Consequences of Sleep-disordered Breathing After SCI
|
N/A | |
Active, not recruiting |
NCT04544761 -
Resilience in Persons Following Spinal Cord Injury
|
||
Terminated |
NCT03170557 -
Randomized Comparative Trial for Persistent Pain in Spinal Cord Injury: Acupuncture vs Aspecific Needle Skin Stimulation
|
N/A | |
Completed |
NCT03220451 -
Use of Adhesive Elastic Taping for the Therapy of Medium/Severe Pressure Ulcers in Spinal Cord Injured Patients
|
N/A | |
Recruiting |
NCT04811235 -
Optical Monitoring With Near-Infrared Spectroscopy for Spinal Cord Injury Trial
|
N/A | |
Recruiting |
NCT04736849 -
Epidural and Dorsal Root Stimulation in Humans With Spinal Cord Injury
|
N/A |