Acute Effects of Pharmacological Neuromodulation on Leg Motor Activity in Patients With SCI Treated With EES — STIMO-PHARMA  

Spinal Cord Injuries Clinical Trial

Official title: Acute Effects of Pharmacological Neuromodulation on Leg Motor Activity in Patients With Spinal Cord Injury Treated With Epidural Electrical Stimulation

Status Completed

Clinical Trial Summary

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.

Clinical Trial Description

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:

1. Spasticity

2. Lower Extremity Motor score (LEMS)

3. Voluntary movements

4. 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. ;

Related Conditions & MeSH terms

• Drug Effect
• Spinal Cord Injuries

• NCT number: NCT04052776
• Study type: Interventional
• Source: Centre Hospitalier Universitaire Vaudois
• Status: Completed
• Phase: Phase 1
• Start date: September 11, 2020
• Completion date: October 4, 2023