A Phase 1 interventional study of Buspirone and Levodopa-Carbidopa in Spinal Cord Injuries and Drug Effect, sponsored by Centre Hospitalier Universitaire Vaudois. Completed at 1 site in Switzerland. Open to participants aged 18 Years to 65 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2023-10-05.
Sponsored by Centre Hospitalier Universitaire Vaudois · Phase 1, Interventional, and Treatment
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.
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:
1,950 studies on the registry are indexed under Spinal Cord Injuries; 507 are open to participants now.
This study's enrollment of 3 is below the median of 24 across 1,567 interventional studies indexed under Spinal Cord Injuries.
Browse Spinal Cord Injuries studies →Centre Hospitalier Universitaire Vaudois is the lead sponsor of 203 studies on the registry; 47 are open to participants now.
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Exclusion Criteria:
Taking selective and non-selective serotonin reuptake inhibitors or any other treatments acting upon serotonergic transmission, such as the following:
40mg
Drug: Buspirone
400mg/100mg
Drug: Levodopa-Carbidopa
40mg + 400mg/100mg
Drug: Buspirone + Levodopa-Carbidopa
Mannitol pill
Drug: Placebo oral tablet
40mg
400mg/100mg
40mg + 400mg/100mg
Non-active metabolite
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
Time frame: Changes from baseline condition over a treatment session of 4 hours
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.
Time frame: Changes from baseline condition over a treatment session of 4 hours
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.
Time frame: Changes from baseline condition over a treatment session of 4 hours
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.
Time frame: Changes from baseline condition over a treatment session of 4 hours
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.
Time frame: Changes from baseline condition over a treatment session of 4 hours
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.
Time frame: Changes from baseline condition over a treatment session of 4 hours
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)
Time frame: Changes from baseline condition over a treatment session of 4 hours
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.
Time frame: Changes from baseline condition over a treatment session of 4 hours
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
Time frame: Changes from baseline condition over a treatment session of 4 hours
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
Time frame: Changes from baseline condition over a treatment session of 4 hours
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.
Time frame: Changes from baseline condition over a treatment session of 4 hours
Plan to share: Yes — The SAP, CSR, AEs, SAEs will be made available to other researchers once the study is completed and data have been analyzed
Supporting information: Sap, Csr
This study is completed, as verified in Oct 2023. You cannot join it, but the record below documents what was studied.
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Centre Hospitalier Universitaire Vaudois