Spinal Cord InjuriesNCT04967274
Reticulospinal Control of Movements
A study testing Startling acoustic stimulus in people with Spinal Cord Injuries and Healthy, run by University of Zurich at 1 site in Switzerland.
Trial summary
Accurate movement execution is a result of a complex interplay between various muscle groups whose activity is controlled by different areas of the central nervous system. Besides the corticospinal system, the phylogenetically old reticulospinal system is a key motor system controlling different elementary movements… Read more about this study
- Who is it for?
- Ages 18 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- Spinal Cord Injuries, Healthy
- What is being tested?
- Startling acoustic stimulus
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 248 participants
- Where
- 1 siteSwitzerland
- Study dates
- 15 Jan 2022to 30 Jun 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Written informed consent as documented by signature
- For SCI patients:
- ASIA Impairment scale (AIS) A-D
- Focal damage at cervical (C4-C7; i.e. damage rostral of the spi-nal segments innervating the examined hand and leg muscles) or thoracic (T4-T12; i.e. damage caudal of the spinal segments innervating the m. abductor digiti minimi, but rostral of the spi-nal segments innervating the m. tibialis anterior)
- Patients with cervical SCI must reveal bilaterally intact ulnar nerves as demonstrated by normal compound motor action potential (cMAP), nerve conduction velocity (NCV) and F-wave latencies in clinical neurography.
- Patients with thoracic SCI must reveal bilaterally intact tibial and peroneal nerves as demonstrated by normal cMAP, NCV and F-wave latencies
Who cannot join
- Women who are pregnant or breast feeding
- Current neurological problems other than SCI and related impairments
- Current orthopaedic problems affecting upper and lower extremity movements
- History of alcohol abuse or the intake of psychotropic drugs
- History of major cardiac condition (e.g., infarction, insufficiency (NYHA II-IV))
- History of major pulmonary condition (e.g., chronic obstructive pulmonary disease (GOLD II-IV))
- Current major depression or psychosis
- Fever of unknown origin
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Switzerland1 site, 1 recruiting
- Recruiting
Balgrist University Hospital
Zurich, 8008
Linard Filli, Dr., +41 44 510 72 12, linard.filli@balgrist.ch
About this study
Official title: Contributions of the Reticulospinal System to Movement Control and Functional Recovery in Patients With Spinal Cord Injury
Accurate movement execution is a result of a complex interplay between various muscle groups whose activity is controlled by different areas of the central nervous system. Besides the corticospinal system, the phylogenetically old reticulospinal system is a key motor system controlling different elementary movements including posture, locomotion and reaching across all mammals. In contrast to the extensively investigated corticospinal system, there is only sparse knowledge on the motor physiology of the functionally important reticulospinal system in humans. Reticulospinal motor control can be assessed with the StartReact paradigm which is based on the activation of reticulospinal motor circuitries by startling acoustic stimuli. The StartReact phenomenon is characterized by a shortening in movement reaction time which is mediated by a startle-triggered, early release of a planned motor program by the reticulospinal system. Thus, StartReact is a unique tool to examine reticulospinal involvement on human motor control under physiological and pathological conditions. StartReact assessments will be supplemented by comprehensive 3-D kinematic analysis and muscle activity recordings (i.e. electromyography) to gain quantitative insights into reticulospinal movement control.
The first objective of this clinical study is to gain more insights into the mechanisms underlying StartReact and to advance the knowledge on reticulo-spinal motor physiology regarding different movement tasks (i.e. simple single-joint movements, complex multi-joint movements and bilateral hand movements) in healthy subjects. The findings of these experiments will provide new insights into proximal-distal, flexor-extensor and upper-lower extremity gradients in reticulospinal motor control of healthy subjects. Moreover, the results will expand the StartReact paradigm to complex, functionally more relevant movements (i.e. reaching and stepping tasks requiring endpoint accuracy; co-operative, bilateral hand movements) for which the involvement of the reticulo-spinal system is not yet understood.
Read more
The second goal of this project is to use the StartReact paradigm to shed more light onto the role of reticulospinal plasticity in functional recovery of patients with spinal cord injury (SCI). Whereas preclinical findings emphasize a remarkable potential of the reticulospinal system for neuroplastic adaptations underlying functional recovery, there is only little evidence from clinical trials in the field of SCI. First, the study aims at monitoring StartReact effects in hand and leg muscles of patients with acute SCI over a period of 6 months. Simultaneous tracking of StartReact effects and motor recovery will allow to closely relate processes of reticulospinal plasticity to functional recovery in patients with acute SCI. Second, the focus will be on the re-weighting of descending motor control (i.e. cortico- vs. reticulospinal system) in response to SCI and investigate the distinct contributions of the cortico- and reticulospinal system to motor recovery in patients with chronic SCI.
The findings of this project will advance the mechanistic understanding on the motor physiology and neurorestorative capacity of the reticulospinal system in humans. New insights from these projects will hopefully translate into a better exploitation of this important motor system in clinical trials that aim to improve motor recovery in patients with SCI.
- Conditions
- Spinal Cord Injuries, Healthy
- Being tested
- Startling acoustic stimulus
- 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.
Startling acoustic stimulusProcedure or surgery
StartReact: involuntary triggering of a planed movement by a loud acoustic stimulus (Transcranial magnetic stimulation).
| Study group | Role | What they receive |
|---|---|---|
| Spinal cord injured subjects | Experimental | Not described Receives: Procedure: Startling acoustic stimulus |
What is being measured
The primary outcome is the main question the study is designed to answer.
EMG analysis (i.e. shortening of movement reaction time of target muscle(s)) during Loud vs. Moderate Acoustic Stimuli (LAS vs. MAS)
Measured: Baseline
Change in EMG analysis (i.e. shortening of movement reaction time of target muscle(s))
Measured: Change in shortening of movement reaction time between baseline and visit 1 (7-14 days).
Change in EMG analysis (i.e. shortening of movement reaction time of target muscle(s))
Measured: Change in shortening of movement reaction time at 3 and 6 months relative to baseline.
Intramuscular coherence of paired EMG signals of the tibialis anterior muscle to assess corticospinal drive in the StartReact paradigm.
Measured: Baseline
Modulation of EMG reflex responses (as induced by electrical ulnar nerve stimulation) by simultaneous acoustic stimulation with LAS
Measured: Baseline
Transcranial magnetic stimulation (TMS) to investigate corticospinal physiology/ integrity.
Measured: Baseline
Secondary outcomes (7)
Analysis of movement patterns of fast vs. slow movements based on 3D kinematics.
Measured: Baseline
Endpoint accuracy of fast vs. slow reaching and stepping movements based on a combined Virtual Reality (VR)/ kinematic system.
Measured: Baseline
Graded Redefined Assessment of Strength, Sensibility, and Prehension (GRASSP) to measure upper extremity function (only for SCI)
Measured: The outcome is used for 2 sub-projects of this study: one sub-project conducts GRASSP at > 12 months after spinal cord injury, whereas the other sub-project conducts GRASSP at 3 visits (at < 1, 3 and 6 months after spinal cord injury).
International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) (only for SCI)
Measured: The outcome is used for 2 sub-projects of this study: one sub-project conducts ISNCSCI at > 12 months after spinal cord injury, whereas the other sub-project conducts ISNCSCI at 3 visits (at < 1, 3 and 6 months after spinal cord injury).
10-meter walk test (only for SCI)
Measured: Baseline
6-minute walk test (only for SCI)
Measured: Baseline
Modified Ashworth Scale (MAS) (only for SCI)
Measured: Baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jul 2021
- Study start15 Jan 2022
- Primary completion30 Jun 2026 (estimated)
- Study completion30 Jun 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Spinal Cord InjuriesStudies of the same condition, open and under way.
- More trials run by University of ZurichThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 N/A
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Each participants receives real and control interventions.
- Masking
- None (open label)
- Enrolment
- 248 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Zurich
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Patrick Freund, Prof. Dr., Principal investigator, University of Zurich
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04967274
- Sponsor's protocol ID
- 2021-00973
- Status last verified
- Oct 2025
- First submitted
- 26 May 2021
- Last updated
- 8 Oct 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Contributions of the Reticulospinal System to Movement Control and Functional Recovery in Patients With Spinal Cord Injury
- ClinicalTrials.gov ID
- NCT04967274
- Acronym / sponsor ID
- 2021-00973
- Conditions
- Spinal Cord Injuries, Healthy
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 248 participants (estimated)
- Lead sponsor
- University of ZurichUniversity, hospital or other
- Study start
- 15 Jan 2022 (actual)
- Primary completion
- 30 Jun 2026 (estimated)
- Study completion
- 30 Jun 2026 (estimated)
- First posted
- 19 Jul 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Accurate movement execution is a result of a complex interplay between various muscle groups whose activity is controlled by different areas of the central nervous system. Besides the corticospinal system, the phylogenetically old reticulospinal system is a key motor system controlling different elementary movements including posture, locomotion and reaching across all mammals. In contrast to the extensively investigated corticospinal system, there is only sparse knowledge on the motor physiology of the functionally important reticulospinal system in humans. Reticulospinal motor control can be assessed with the StartReact paradigm which is based on the activation of reticulospinal motor circuitries by startling acoustic stimuli. The StartReact phenomenon is characterized by a shortening in movement reaction time which is mediated by a startle-triggered, early release of a planned motor program by the reticulospinal system. Thus, StartReact is a unique tool to examine reticulospinal involvement on human motor control under physiological and pathological conditions. StartReact assessments will be supplemented by comprehensive 3-D kinematic analysis and muscle activity recordings (i.e. electromyography) to gain quantitative insights into reticulospinal movement control.
The first objective of this clinical study is to gain more insights into the mechanisms underlying StartReact and to advance the knowledge on reticulo-spinal motor physiology regarding different movement tasks (i.e. simple single-joint movements, complex multi-joint movements and bilateral hand movements) in healthy subjects. The findings of these experiments will provide new insights into proximal-distal, flexor-extensor and upper-lower extremity gradients in reticulospinal motor control of healthy subjects. Moreover, the results will expand the StartReact paradigm to complex, functionally more relevant movements (i.e. reaching and stepping tasks requiring endpoint accuracy; co-operative, bilateral hand movements) for which the involvement of the reticulo-spinal system is not yet understood.
The second goal of this project is to use the StartReact paradigm to shed more light onto the role of reticulospinal plasticity in functional recovery of patients with spinal cord injury (SCI). Whereas preclinical findings emphasize a remarkable potential of the reticulospinal system for neuroplastic adaptations underlying functional recovery, there is only little evidence from clinical trials in the field of SCI. First, the study aims at monitoring StartReact effects in hand and leg muscles of patients with acute SCI over a period of 6 months. Simultaneous tracking of StartReact effects and motor recovery will allow to closely relate processes of reticulospinal plasticity to functional recovery in patients with acute SCI. Second, the focus will be on the re-weighting of descending motor control (i.e. cortico- vs. reticulospinal system) in response to SCI and investigate the distinct contributions of the cortico- and reticulospinal system to motor recovery in patients with chronic SCI.
The findings of this project will advance the mechanistic understanding on the motor physiology and neurorestorative capacity of the reticulospinal system in humans. New insights from these projects will hopefully translate into a better exploitation of this important motor system in clinical trials that aim to improve motor recovery in patients with SCI.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Each participants receives real and control interventions.
| Arm | Type | Receives |
|---|---|---|
| Spinal cord injured subjects | Experimental | Procedure: Startling acoustic stimulus |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Written informed consent as documented by signature
- ASIA Impairment scale (AIS) A-D
- Focal damage at cervical (C4-C7; i.e. damage rostral of the spi-nal segments innervating the examined hand and leg muscles) or thoracic (T4-T12; i.e. damage caudal of the spinal segments innervating the m. abductor digiti minimi, but rostral of the spi-nal segments innervating the m. tibialis anterior)
- Patients with cervical SCI must reveal bilaterally intact ulnar nerves as demonstrated by normal compound motor action potential (cMAP), nerve conduction velocity (NCV) and F-wave latencies in clinical neurography.
- Patients with thoracic SCI must reveal bilaterally intact tibial and peroneal nerves as demonstrated by normal cMAP, NCV and F-wave latencies
Key exclusion criteria (8 listed)
- Women who are pregnant or breast feeding
- Current neurological problems other than SCI and related impairments
- Current orthopaedic problems affecting upper and lower extremity movements
- History of alcohol abuse or the intake of psychotropic drugs
- History of major cardiac condition (e.g., infarction, insufficiency (NYHA II-IV))
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Startling acoustic stimulusStartReact: involuntary triggering of a planed movement by a loud acoustic stimulus (Transcranial magnetic stimulation). | Procedure or surgery | Spinal cord injured subjects |
Primary outcome
EMG analysis (i.e. shortening of movement reaction time of target muscle(s)) during Loud vs. Moderate Acoustic Stimuli (LAS vs. MAS)
Time frame: Baseline
Change in EMG analysis (i.e. shortening of movement reaction time of target muscle(s))
Time frame: Change in shortening of movement reaction time between baseline and visit 1 (7-14 days).
Change in EMG analysis (i.e. shortening of movement reaction time of target muscle(s))
Time frame: Change in shortening of movement reaction time at 3 and 6 months relative to baseline.
Intramuscular coherence of paired EMG signals of the tibialis anterior muscle to assess corticospinal drive in the StartReact paradigm.
Time frame: Baseline
Modulation of EMG reflex responses (as induced by electrical ulnar nerve stimulation) by simultaneous acoustic stimulation with LAS
Time frame: Baseline
Transcranial magnetic stimulation (TMS) to investigate corticospinal physiology/ integrity.
Time frame: Baseline
7 secondary outcomes
Analysis of movement patterns of fast vs. slow movements based on 3D kinematics.
Time frame: Baseline
Endpoint accuracy of fast vs. slow reaching and stepping movements based on a combined Virtual Reality (VR)/ kinematic system.
Time frame: Baseline
Graded Redefined Assessment of Strength, Sensibility, and Prehension (GRASSP) to measure upper extremity function (only for SCI)
Time frame: The outcome is used for 2 sub-projects of this study: one sub-project conducts GRASSP at > 12 months after spinal cord injury, whereas the other sub-project conducts GRASSP at 3 visits (at < 1, 3 and 6 months after spinal cord injury).
International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) (only for SCI)
Time frame: The outcome is used for 2 sub-projects of this study: one sub-project conducts ISNCSCI at > 12 months after spinal cord injury, whereas the other sub-project conducts ISNCSCI at 3 visits (at < 1, 3 and 6 months after spinal cord injury).
10-meter walk test (only for SCI)
Time frame: Baseline
6-minute walk test (only for SCI)
Time frame: Baseline
Modified Ashworth Scale (MAS) (only for SCI)
Time frame: Baseline
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Oct 2025.
Related trials for Spinal Cord Injuries
Recruiting
Implant for Walking After Incomplete SCI
Spinal Cord Injury (SCI), Gait
Recruiting
MindEx: A Novel, Multifocal, Cognitive Brain-Machine Interface System
Paralysis; Quadriplegic, Quadraplegia
Recruiting
tSCS Combined With Rehabilitation Training in Treating Paraplegic Patients After SCI
Spinal Cord Injury, Paraplegia, Spinal
Active, not recruitingObservational study
Natural History of Shoulder Pathology in Manual Wheelchair Users
Paraplegia, Spinal Cord Injuries
Recruiting
Neuromodulation for Metabolic Dysfunction
Spinal Cord Injuries (SCI), Prediabetes / Type 2 Diabetes
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Patrick Freund, Prof. Dr. principal investigator
University of Zurich
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Startling acoustic stimulus in people with Spinal Cord Injuries and Healthy, run by University of Zurich 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 6 inclusion and 8 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: looking for participants now, as of the sponsor's last update on 8 Oct 2025. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Linard Filli, Dr. (+41 44 510 72 12, linard.filli@balgrist.ch), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
EMG analysis (i.e. shortening of movement reaction time of target muscle(s)) during Loud vs. Moderate Acoustic Stimuli (LAS vs. MAS) (time frame: Baseline). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 8 Oct 2025.