Acute Effects of Pharmacological Neuromodulation on Leg Motor Activity in Patients With SCI Treated With EES

The aim is to test the effects of orally administered buspirone and levodopa/carbidopa taken individually and in combination. Both buspirone and levodopa can cross the blood-brain barrier, and reach the lumbar spinal cord where 5-HT1A receptors are expressed, and levodopa can presumably be synthesized by specialized dopaminergic into dopamine. Alternatively, levodopa effects might be mediated via noradrenaline, following dopamine metabolization. Therefore, it is hypothesized that the combination of pharmacological neuromodulation with EES would further improve locomotor functions and lower extremity motor score.

The primary and safety objective is to evaluate the safety and the tolerability of a single-dose of immediate-release levodopa/carbidopa, buspirone, the combination levodopa/carbidopa and buspirone, and the placebo in individuals with SCI.

The secondary objectives are to assess the following effects of levodopa/carbidopa, buspirone, the combination levodopa/carbidopa and buspirone, and the placebo on the lower extremities:

• Spasticity
• Lower Extremity Motor score (LEMS)
• Voluntary movements
• Gait patterns and velocity Participants' safety will be ensured with the usage of Rysen, which a CE-marked bodyweight support system robot, and the aid of locomotor assistive device.

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.)