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| Name | Class |
|---|---|
| Roche-Genentech | INDUSTRY |
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Spinal cord stimulation (SCS) has shown remarkable efficacy in restoring motor function in people with spinal cord injury by recruiting afferent input to enhance the responsiveness of spared neural circuits to residual cortical inputs. This pilot will test if SCS can show evidence to improve motor deficits in people with type 3 or 4 spinal muscular atrophy (SMA). The investigators will enroll up to six subjects with Type 3 or 4 SMA aged 16 or older that show quantifiable motor deficits of the legs but are able to stand independently. The investigators will then implant the subjects with percutaneous, bilateral, linear spinal leads near the lumbar spinal cord for a period of up to 29 days. Although these leads are not optimized for motor function but rather for their clinically approved indication of treating pain, the investigators believe they provide a safe technology enabling our team to perform scientific measurement necessary to evaluate potential for effects of SCS in motor paralysis with SMA. After the end of the study, the leads will be explanted.
The investigators plan to 1. verify that spinal cord stimulation increases hip muscle strength in subjects with SMA, 2. verify that spinal cord stimulation improves motor control in subjects with SMA, 3. verify that spinal cord stimulation induces measurable changes in spinal circuits and motoneuron recruitment properties in the 29 day course of implantation.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Spinal Cord Stimulation | Experimental | All patients will receive FDA-approved percutaneous spinal cord stimulation leads implanted in the epidural (T12-L2 vertebra) space. The leads will be connected to external stimulators (either FDA-approved or human-grade research stimulator with safety features) during research activities. |
|
| Control Arm | No Intervention | Healthy volunteers may be enrolled for comparison data for those who have received the spinal cord leads. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Spinal Cord Stimulator (octopolar Medtronic Vectris Leads) | Device | 2-4 leads FDA-approved for treatment of symptoms of refractory pain |
|
| Measure | Description | Time Frame |
|---|---|---|
| Muscle Weakness | Isometric torque: measure the isometric torque produced by the subject at the hip during hip-flexion. Comparison of SCS-on with SCS-off performance. Success Criteria: ≥20% increased torque production over SCS-off baseline as measured during single-joint isometric torque. | 29 days |
| Number of Participants With Adverse Events | Success Criteria: no serious adverse event related to the stimulation or intolerable adverse event reported | 29 days |
| Measure | Description | Time Frame |
|---|---|---|
| Motor Function ROM | Range of Motion (ROM): Meaningful Change: increase of >20% of the hip joint (if available) and the knee joint (if available) during SCS against SCS-off as measured by the HUMAC NORM during single-joint isotonic trials. | 29 days |
| Muscle Weakness 2 |
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Inclusion Criteria:
Subject or subject's parent or legal guardian (for minor subjects) has provided written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization, where applicable, prior to any study-related procedures. Minor subjects will be asked to give written assent according to local requirements.
Subject has a diagnosis of 5q-autosomal recessive SMA confirmed by determination of a genetic deletion in the SMN1 gene (5q12.2-q13.3)
Subject is diagnosed as having Type 3 or Type 4 SMA based on the following criteria
Subject is ≥16 years of age and < 65 years of age
Subject is able to stand independently for ≥3 seconds
RHS score lower or equal to 65
Subject (and subject's parent or legal guardian if subject is a minor) is willing and able to comply with scheduled visits and study procedures
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Marco Capogrosso | University of Pittsburgh | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Pittsburgh | Pittsburgh | Pennsylvania | 15213 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 39910271 | Derived | Prat-Ortega G, Ensel S, Donadio S, Borda L, Boos A, Yadav P, Verma N, Ho J, Carranza E, Frazier-Kim S, Fields DP, Fisher LE, Weber DJ, Balzer J, Duong T, Weinstein SD, Eliasson MJL, Montes J, Chen KS, Clemens PR, Gerszten P, Mentis GZ, Pirondini E, Friedlander RM, Capogrosso M. First-in-human study of epidural spinal cord stimulation in individuals with spinal muscular atrophy. Nat Med. 2025 Apr;31(4):1246-1256. doi: 10.1038/s41591-024-03484-8. Epub 2025 Feb 5. |
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Data may be shared with other researchers for the purpose of data analysis and collaboration.
Data will become available at the end of the trial upon publication of the first manuscript. Estimation is 2 years from enrollment of first participant
Data must be directly requested to the PI and will be shared upon completion of necessary data sharing agreement to protect confidential patient information
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| ID | Title | Description |
|---|---|---|
| FG000 | Spinal Cord Stimulation | All patients will receive FDA-approved percutaneous spinal cord stimulation leads implanted in the epidural (T12-L2 vertebra) space. The leads will be connected to external stimulators (either FDA-approved or human-grade research stimulator with safety features) during research activities. The control arm was not executed, as there was a lack of funding. Therefore, this was a single arm study only implanting the leads into participants with SMA. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
All participants enrolled were implanted with the spinal cord stimulator.
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| ID | Title | Description |
|---|---|---|
| BG000 | Spinal Cord Stimulation | All patients will receive FDA-approved percutaneous spinal cord stimulation leads implanted in the epidural (T12-L2 vertebra) space. The leads will be connected to external stimulators (either FDA-approved or human-grade research stimulator with safety features) during research activities. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Muscle Weakness | Isometric torque: measure the isometric torque produced by the subject at the hip during hip-flexion. Comparison of SCS-on with SCS-off performance. Success Criteria: ≥20% increased torque production over SCS-off baseline as measured during single-joint isometric torque. | Isometric hip flexion torque during maximum voluntary contraction was measured using a HUMAC NORM dynamometer. Assistive effects were assessed by comparing SCS-ON vs SCS-OFF within the same session, and therapeutic effects by comparing post-explant vs pre-implant torque. For both assistive and therapeutic analyses, we report the number of participants who achieved a ≥20% increase in hip flexion torque. | Posted | Count of Participants | Participants | 29 days |
|
29 days
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Spinal Cord Stimulation | All patients will receive FDA-approved percutaneous spinal cord stimulation leads implanted in the epidural (T12-L2 vertebra) space. The leads will be connected to external stimulators (either FDA-approved or human-grade research stimulator with safety features) during research activities. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Fall | General disorders | Non-systematic Assessment | Fall would indicate any loss of stability resulting in participant losing their balance and may or may not reach the ground. No falls in this study resulted in any injury. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Marco Capogrosso - PI | University of Pittsburgh | +14123702435 | mcapo@pitt.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jan 13, 2025 | Jan 8, 2026 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D014897 | Spinal Muscular Atrophies of Childhood |
| D009134 | Muscular Atrophy, Spinal |
| ID | Term |
|---|---|
| D013118 | Spinal Cord Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D020271 | Heredodegenerative Disorders, Nervous System |
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Single-arm, open-label study performed to quantify variables that are predictive of the efficacy of spinal cord stimulation to improve motor control.
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Muscle activation: measure surface EMGs produced by the subjects during isometric movements of the hip, knee, and ankle in the HUMAC Norm and compare SCS-on with SCS-off performances. Meaningful Change:<20% EMG RMS compared to SCS-on. |
| 29 days |
| Motor Function: 6-Minute Walk Test | 6 minute walk test: perform the 6-minute walk test with SCS-on and SCS-off and distance between SCS-on and SCS-off is set to 24 m. If not ambulatory, any increased ambulation distance from SCS-off condition. | 29 days |
| Motor Function: Fatigue | Fatigue will be assessed during motor function tests. | 29 days |
| Motor Function RHS | The Revised Hammersmith Functional Scale is a further refined version of the Hammersmith Functional Motor Scale Extended and includes specific items focused on lower-limb motor control such as hip-flexion, standing and walking a that are particularly relevant for the type III population of study. The scale is a 36 item performance evaluation, with a score range from 0-69 in which higher scores indicate better performance. Meaningful Change: ≥2 point improvement. Compare outcomes between SCS-on and SCS-off. Motor Function Measure 32. The 32 items MFM is often used in trials of neuromuscular disorders, hence it provides a meaningful comparison against outcomes of other trials. Meaningful Change: ≥2 point improvement. Compare outcomes between SCS-on and SCS-off. | 29 days |
| Number of Participants With Discomfort/Pain | Patients will be asked to provide a score from 1 to 10 where a greater number indicates a greater amount of discomfort for each stimulation configuration. Spinal cord stimulation produces tingling sensations and other type of sensory phenomena. It is important to document that stimulation intensities required to improve motor function remain within a range of non-painful sensations. | 29 days |
| Sensorimotor Network Structure Density | The investigators will perform High-definition Diffusion Weighted Imaging to quantify Fractional Anisotropy as a measurement of axon density in the brain and spinal cord pre and post study. | 29 days |
| Impression | The investigators will collect subjects and therapist feedback on how the technology is performing and what they would want to modify using The Clinical Global Impression Scale, a scale of 1-7 where a lower number indicates better performance and a higher number indicates more greatly impacted by their disease. | 29 days |
| Sensorimotor Network Structure Integrity | The investigators will perform High-definition Diffusion Weighted Imaging to quantify Fractional Anisotropy as a measurement of axon integrity in the brain and spinal cord pre and post study. | 29 days |
| Sensorimotor Network Function | The investigators will perform resting state and motor-task functional MRI of the brain and spinal cord to quantify neural network activation at rest and during the execution of simple motor task such as leg muscle contraction. | 29 days |
| Cortico-spinal Tract Integrity | The investigators will measure muscle evoked potential consequent to Transcranial Magnetic Stimulation of the cortico-spinal tract to assess integrity of the cortico-spinal tract. | 29 days |
| Spinal Circuit Excitability | The investigators will measure H-reflexes of leg muscles to quantify excitability of spinal motoneurons to stimulation of primary sensory afferents pre and post-study. Expected Result: Our main scientific hypothesis is that SCS will restore monosynaptic responses of weak spinal motoneurons, thus increasing H-reflex responses pre and post-study. | 29 days |
| Motoneuron Firing Rates | The investigators will use high-density EMGs on leg muscles to calculate firing rates of single spinal motoneuron discharge during isometric maximal voluntary contractions. | 29 days |
| Motor Firing Number | The investigators will use high-density EMGs on leg muscles to calculate the number of firing rates of single spinal motoneuron discharge during isometric maximal voluntary contractions. | 29 days |
| Participants |
| No |
|
| Sex: Female, Male | Count of Participants | Participants | No |
|
| Motor Function: 6-Minute Walk Test | The 6-Minute Walk Test (6MWT) is a submaximal assessment of endurance and aerobic capacity. Participants are instructed to walk as far as possible for 6 minutes, and total distance covered is recorded in a standardized setting. The same licensed therapist administered and scored the 6MWT at both the pre-study baseline and post-study assessment. | We reported for each participant the total distance walked at the pre-study assessment. | Number | meter |
|
| Motor Function RHS | The Revised Hammersmith Scale (RHS) is a 36-item performance measure with scores ranging from 0 to 69, where higher scores indicate better motor function. The same licensed therapist administered and scored the assessment throughout the study. Here we report the baseline RHS scores to illustrate the heterogeneity of the participants enrolled. | We reported the score independently for each participant. | Number | Score |
|
| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
|
|
|
| Primary | Number of Participants With Adverse Events | Success Criteria: no serious adverse event related to the stimulation or intolerable adverse event reported | Posted | Count of Participants | Participants | 29 days |
|
|
|
| Secondary | Motor Function ROM | Range of Motion (ROM): Meaningful Change: increase of >20% of the hip joint (if available) and the knee joint (if available) during SCS against SCS-off as measured by the HUMAC NORM during single-joint isotonic trials. | Therapeutic changes in hip and knee range of motion were assessed by comparing pre- and post-study measurements, and we reported the number of participants meeting the predefined success criteria. | Posted | Count of Participants | Participants | 29 days |
|
|
|
| Secondary | Muscle Weakness 2 | Muscle activation: measure surface EMGs produced by the subjects during isometric movements of the hip, knee, and ankle in the HUMAC Norm and compare SCS-on with SCS-off performances. Meaningful Change:<20% EMG RMS compared to SCS-on. | We assessed EMG RMS activity of the hip and knee extensors during walking pre-implant and post-explant. Post-explant EMG analysis was possible for 2 of the 3 participants. We report the number of participants with analyzable data who met the prespecified success criterion (>20% increase in EMG RMS post-explant vs pre-implant); | Posted | Count of Participants | Participants | 29 days |
|
|
|
| Secondary | Motor Function: 6-Minute Walk Test | 6 minute walk test: perform the 6-minute walk test with SCS-on and SCS-off and distance between SCS-on and SCS-off is set to 24 m. If not ambulatory, any increased ambulation distance from SCS-off condition. | The 6-minute walk test (6MWT) was conducted pre-implant and post-explant. For each participant, change in distance walked was calculated as the post-explant value minus the pre-implant value. We report the number of participants who increased 6MWT distance by ≥24 m. | Posted | Number | participants | 29 days |
|
|
|
| Secondary | Motor Function: Fatigue | Fatigue will be assessed during motor function tests. | Fatigability was quantified using a fatigability index, defined as the percent change in walking velocity from the first lap to the last lap of the 6-minute walk test (6MWT). For each participant, therapeutic change was calculated as the difference in fatigability index from pre-study to post-study (post - pre). We report the number of participants who showed a ≥10% decrease in the fatigability index. | Posted | Number | participants | 29 days |
|
|
|
| Secondary | Motor Function RHS | The Revised Hammersmith Functional Scale is a further refined version of the Hammersmith Functional Motor Scale Extended and includes specific items focused on lower-limb motor control such as hip-flexion, standing and walking a that are particularly relevant for the type III population of study. The scale is a 36 item performance evaluation, with a score range from 0-69 in which higher scores indicate better performance. Meaningful Change: ≥2 point improvement. Compare outcomes between SCS-on and SCS-off. Motor Function Measure 32. The 32 items MFM is often used in trials of neuromuscular disorders, hence it provides a meaningful comparison against outcomes of other trials. Meaningful Change: ≥2 point improvement. Compare outcomes between SCS-on and SCS-off. | We report the change in RHFS score from baseline to post-explant. End-of-study assessments were available for only two participants because SMA01 could not complete the final evaluation due to the explant surgery schedule. We report the number of assessed participants who met the prespecified success criterion, defined as an increase in RHFS score of ≥2 points from baseline. | Posted | Count of Participants | Participants | 29 days |
|
|
|
| Secondary | Number of Participants With Discomfort/Pain | Patients will be asked to provide a score from 1 to 10 where a greater number indicates a greater amount of discomfort for each stimulation configuration. Spinal cord stimulation produces tingling sensations and other type of sensory phenomena. It is important to document that stimulation intensities required to improve motor function remain within a range of non-painful sensations. | We report the number of participants who reported discomfort/pain ≥ 3/10 on the 1-10 scale | Posted | Count of Participants | Participants | 29 days |
|
|
|
| Secondary | Sensorimotor Network Structure Density | The investigators will perform High-definition Diffusion Weighted Imaging to quantify Fractional Anisotropy as a measurement of axon density in the brain and spinal cord pre and post study. | The sensorimotor network structure density analysis data were not collected because it required time-matched acquisition during the fMRI session. Collecting both measures in the same visit would have substantially increased scan duration; to minimize participant burden and discomfort, these data were not obtained. | Posted | Count of Participants | Participants | 29 days |
|
|
|
| Secondary | Impression | The investigators will collect subjects and therapist feedback on how the technology is performing and what they would want to modify using The Clinical Global Impression Scale, a scale of 1-7 where a lower number indicates better performance and a higher number indicates more greatly impacted by their disease. | CGI rating was not collected because adding this assessment would have extended study visits. To minimize participant burden and prioritize the prespecified study outcomes, CGI data were not obtained. | Posted | Count of Participants | Participants | 29 days |
|
|
|
| Secondary | Sensorimotor Network Structure Integrity | The investigators will perform High-definition Diffusion Weighted Imaging to quantify Fractional Anisotropy as a measurement of axon integrity in the brain and spinal cord pre and post study. | The sensorimotor network structure integrity analysis data were not collected because it required time-matched acquisition during the fMRI session. Collecting both measures in the same visit would have substantially increased scan duration; to minimize participant burden and discomfort, these data were not obtained. | Posted | Count of Participants | Participants | 29 days |
|
|
|
| Secondary | Sensorimotor Network Function | The investigators will perform resting state and motor-task functional MRI of the brain and spinal cord to quantify neural network activation at rest and during the execution of simple motor task such as leg muscle contraction. | Functional MRI (fMRI) sequences were developed to image the lumbosacral spinal cord while participants performed volitional knee flexion and extension. These scans yielded detectable blood-oxygenation-level-dependent (BOLD) signal changes during the motor task within lumbosacral regions associated with knee motor output. We report the number of participants with analyzable data whose task-evoked BOLD signal was statistically significantly higher at post-study than at pre-study. | Posted | Count of Participants | Participants | 29 days |
|
|
|
| Secondary | Cortico-spinal Tract Integrity | The investigators will measure muscle evoked potential consequent to Transcranial Magnetic Stimulation of the cortico-spinal tract to assess integrity of the cortico-spinal tract. | Motoneuron excitability was assessed using transcranial magnetic stimulation (TMS). Peak-to-peak motor evoked potential (MEP) amplitudes were recorded following single TMS pulses delivered to the leg area of the primary motor cortex. MEP amplitudes were measured at pre-study and post-study sessions. We report the number of participants who showed a statistically significant decrease in MEP peak-to-peak amplitude at post-explant compared with baseline (pre-implant). | Posted | Count of Participants | Participants | 29 days |
|
|
|
| Secondary | Spinal Circuit Excitability | The investigators will measure H-reflexes of leg muscles to quantify excitability of spinal motoneurons to stimulation of primary sensory afferents pre and post-study. Expected Result: Our main scientific hypothesis is that SCS will restore monosynaptic responses of weak spinal motoneurons, thus increasing H-reflex responses pre and post-study. | Changes in sensory-to-motoneuron synaptic responsiveness were assessed by measuring spinal sensory reflexes evoked by single-pulse of SCS delivered to the lower-limb muscles during the first and last week of the implant period. We report the number of participants with analyzable data who showed no decrease in reflex response over time (i.e., reflex responses were unchanged or increased at the last-week assessment compared with the first-week assessment) | Posted | Count of Participants | Participants | 29 days |
|
|
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| Secondary | Motoneuron Firing Rates | The investigators will use high-density EMGs on leg muscles to calculate firing rates of single spinal motoneuron discharge during isometric maximal voluntary contractions. | During maximum voluntary contractions, high-density EMG (HD-EMG) was recorded and the signals were decomposed to identify motor unit discharge times. Peak motor unit firing rate was quantified, and we report the number of participants who exhibited a statistically significant increase in peak firing rate post-explant compared with pre-implant. | Posted | Count of Participants | Participants | 29 days |
|
|
|
| Secondary | Motor Firing Number | The investigators will use high-density EMGs on leg muscles to calculate the number of firing rates of single spinal motoneuron discharge during isometric maximal voluntary contractions. | During maximum voluntary contractions, high-density EMG (HD-EMG) was recorded and the signals were decomposed to identify motor units. We report the number of participants who showed a statistically significant increase in the number of detected motor units at post-explant compared with pre-implant | Posted | Count of Participants | Participants | 29 days |
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| 0 |
| 3 |
| 0 |
| 3 |
| 3 |
| 3 |
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| D019636 | Neurodegenerative Diseases |
| D016472 | Motor Neuron Disease |
| D009468 | Neuromuscular Diseases |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |