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Spinal Cord InjuriesPhase 1STIMO-PHARMANCT04052776

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

A Phase 1 study testing Buspirone, Levodopa-Carbidopa and Buspirone + Levodopa-Carbidopa in people with Spinal Cord Injuries and Drug Effect, run by Centre Hospitalier Universitaire Vaudois at 1 site in Switzerland.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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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… Read more about this study

Who is it for?
Ages 18 to 65 yearsHealthy volunteers can take part
Conditions the study is for
Spinal Cord Injuries, Drug Effect
What is being tested?
Buspirone, Levodopa-Carbidopa and Buspirone + Levodopa-Carbidopa
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
3 participants
Where
1 siteSwitzerland
Study dates
11 Sep 2020to 4 Oct 2023
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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.
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  • 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.)

Trial locations and contacts

1 site in 1 country.

Switzerland1 site
  • CHUV

    Lausanne, Canton of Vaud, 1011

Other trials in Switzerland

About this study

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

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.

Read the detailed 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.
Being tested
Buspirone, Levodopa-Carbidopa, Buspirone + Levodopa-Carbidopa, Placebo oral tablet
Keywords
Pharmacology, Neuromodulation, Epidural electrical stimulation
Medical subject headings
Spinal Cord Injuries

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BuspironeDrug

    40mg

  • Levodopa-CarbidopaDrug

    400mg/100mg

  • Buspirone + Levodopa-CarbidopaDrug

    40mg + 400mg/100mg

  • Placebo oral tabletDrug

    Non-active metabolite

Study groups in NCT04052776
Study groupRoleWhat they receive
BuspironeActive comparator40mg
Receives: Drug: Buspirone
Levodopa-CarbidopaActive comparator400mg/100mg
Receives: Drug: Levodopa-Carbidopa
Buspirone + Levodopa-CarbidopaActive comparator40mg + 400mg/100mg
Receives: Drug: Buspirone + Levodopa-Carbidopa
PlaceboPlacebo comparatorMannitol pill
Receives: Drug: Placebo oral tablet

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: Changes from baseline condition over a treatment session of 4 hours

  2. 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.

    Measured: Changes from baseline condition over a treatment session of 4 hours

  3. 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.

    Measured: Changes from baseline condition over a treatment session of 4 hours

Secondary outcomes (8)
  1. 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.

    Measured: Changes from baseline condition over a treatment session of 4 hours

  2. 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.

    Measured: Changes from baseline condition over a treatment session of 4 hours

  3. 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.

    Measured: Changes from baseline condition over a treatment session of 4 hours

  4. 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)

    Measured: Changes from baseline condition over a treatment session of 4 hours

  5. 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.

    Measured: Changes from baseline condition over a treatment session of 4 hours

  6. 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

    Measured: Changes from baseline condition over a treatment session of 4 hours

  7. 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

    Measured: Changes from baseline condition over a treatment session of 4 hours

  8. 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.

    Measured: Changes from baseline condition over a treatment session of 4 hours

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Aug 2019
  2. Study start11 Sep 2020
  3. Primary completion4 Oct 2023
  4. Study completion4 Oct 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Crossover
Model description
This study will be monocentric, randomized, double-blind, placebo-controlled with a four-sequence crossover design. All participants will undergo the 4 treatment arms. and each of them will be their own control.
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
3 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04052776
Sponsor's protocol ID
2019-01057
Other IDs
2019
Acronym
STIMO-PHARMA
Status last verified
Oct 2023
First submitted
29 Jul 2019
Last updated
5 Oct 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: The SAP, CSR, AEs, SAEs will be made available to other researchers once the study is completed and data have been analyzed

Publications

  • 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.

    PubMed 30382197
  • 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.

    PubMed 30382196

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Buspirone, Levodopa-Carbidopa and Buspirone + Levodopa-Carbidopa in people with Spinal Cord Injuries and Drug Effect, run by Centre Hospitalier Universitaire Vaudois at 1 site in Switzerland.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 5 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Rate of AEs/SAEs/Side effects (time frame: Changes from baseline condition over a treatment session of 4 hours). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04052776, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Oct 2023.

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