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Spinal Cord Stimulation in Spinal Muscular Atrophy (SCSinSMA)

Primary Purpose

Spinal Muscular Atrophy Type 3, Spinal Muscular Atrophy Type 4

Status

Recruiting

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

Spinal Cord Stimulator (octopolar Medtronic Vectris Leads)

About this trial

This is an interventional basic science trial for Spinal Muscular Atrophy Type 3 focused on measuring Spinal Muscular Atrophy, Spinal Cord Stimulation

Eligibility Criteria

16 Years - 64 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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
1. Disease manifested after 18 months of age
2. Disease manifested after ambulation was acquired
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:

Subject has deformation of the spinal canal preventing lead implantation as judged by the study neurosurgeon
Subject has size of spinal canal that is insufficient for lead implantation as judged by the study neurosurgeon
Subject has moderate or severe joint contractures that would affect ability to perform study measures
Subject has severe behavioral or cognitive problems that preclude participation in the study, in the opinion of the investigator
Subject has previous or ongoing medical condition, medical history, physical findings or laboratory abnormalities that could affect safety of anesthesia or the procedures, make it unlikely that intervention or follow-up will be correctly completed or impair the assessment of study results, in the opinion of the investigator
Female subjects are pregnant or breastfeeding
Subject has severe claustrophobia
Subject is on anticoagulant, anti-spasticity or anti-seizure medication within 4 weeks of lead implantation or requires these medications during the treatment phase of the study
Subject has medical implant that precludes magnetic resonance imaging

Sites / Locations

University of PittsburghRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Spinal Cord Stimulation

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

Number and Severity of Adverse Events

Success Criteria: no serious adverse event related to the stimulation or intolerable adverse event reported

Secondary Outcome Measures

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.

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.

Motor Function: 6-Minute Walk Teset

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 ambulator, any increased ambulation distance from SCS-off condition.

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.

Motor Function: Fatigue

Fatigue will be assessed during motor function tests.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Full Information

NCT ID

NCT05430113

First Posted

April 12, 2022

Last Updated

June 13, 2023

Sponsor

Marco Capogrosso

Collaborators

Roche-Genentech

1. Study Identification

Unique Protocol Identification Number

NCT05430113

Brief Title

Spinal Cord Stimulation in Spinal Muscular Atrophy

Acronym

SCSinSMA

Official Title

Spinal Cord Stimulation for the Treatment of Motor Deficits in People With Spinal Muscular Atrophy

Study Type

Interventional

2. Study Status

Record Verification Date

June 2023

Overall Recruitment Status

Recruiting

Study Start Date

April 5, 2022 (Actual)

Primary Completion Date

September 2026 (Anticipated)

Study Completion Date

August 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Marco Capogrosso

Collaborators

Roche-Genentech

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Yes

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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.

Detailed Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Spinal Muscular Atrophy Type 3, Spinal Muscular Atrophy Type 4

Keywords

Spinal Muscular Atrophy, Spinal Cord Stimulation

7. Study Design

Primary Purpose

Basic Science

Study Phase

Not Applicable

Interventional Study Model

Single Group Assignment

Model Description

Single-arm, open-label study performed to quantify variables that are predictive of the efficacy of spinal cord stimulation to improve motor control.

Masking

None (Open Label)

Allocation

N/A

Enrollment

10 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Spinal Cord Stimulation

Arm Type

Experimental

Arm Description

Intervention Type

Device

Intervention Name(s)

Spinal Cord Stimulator (octopolar Medtronic Vectris Leads)

Intervention Description

2-4 leads FDA-approved for treatment of symptoms of refractory pain

Primary Outcome Measure Information:

Title

Muscle Weakness

Description

Time Frame

29 days

Title

Number and Severity of Adverse Events

Description

Success Criteria: no serious adverse event related to the stimulation or intolerable adverse event reported

Time Frame

29 days

Secondary Outcome Measure Information:

Title

Muscle Weakness 2

Description

Time Frame

29 days

Title

Motor Function ROM

Description

Time Frame

29 days

Title

Motor Function: 6-Minute Walk Teset

Description

Time Frame

29 days

Title

Motor Function RHS

Description

Time Frame

29 days

Title

Motor Function: Fatigue

Description

Fatigue will be assessed during motor function tests.

Time Frame

29 days

Title

Discomfort/Pain

Description

Time Frame

29 days

Title

Sensorimotor Network Structure Density

Description

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.

Time Frame

29 days

Title

Impression

Description

Time Frame

29 days

Title

Sensorimotor Network Structure Integrity

Description

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.

Time Frame

29 days

Title

Sensorimotor Network Function

Description

Time Frame

29 days

Title

Cortico-spinal Tract Integrity

Description

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.

Time Frame

29 days

Title

Spinal Circuit Excitability

Description

Time Frame

29 days

Title

Motoneuron Firing Rates

Description

The investigators will use high-density EMGs on leg muscles to calculate firing rates of single spinal motoneuron discharge during isometric maximal voluntary contractions.

Time Frame

29 days

Title

Motor Firing Number

Description

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.

Time Frame

29 days

10. Eligibility

Sex

All

Minimum Age & Unit of Time

16 Years

Maximum Age & Unit of Time

64 Years

Accepts Healthy Volunteers

Eligibility Criteria

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 Disease manifested after 18 months of age Disease manifested after ambulation was acquired 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: Subject has deformation of the spinal canal preventing lead implantation as judged by the study neurosurgeon Subject has size of spinal canal that is insufficient for lead implantation as judged by the study neurosurgeon Subject has moderate or severe joint contractures that would affect ability to perform study measures Subject has severe behavioral or cognitive problems that preclude participation in the study, in the opinion of the investigator Subject has previous or ongoing medical condition, medical history, physical findings or laboratory abnormalities that could affect safety of anesthesia or the procedures, make it unlikely that intervention or follow-up will be correctly completed or impair the assessment of study results, in the opinion of the investigator Female subjects are pregnant or breastfeeding Subject has severe claustrophobia Subject is on anticoagulant, anti-spasticity or anti-seizure medication within 4 weeks of lead implantation or requires these medications during the treatment phase of the study Subject has medical implant that precludes magnetic resonance imaging

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Sydney Bader, MS

Phone

412-648-4196

syb17@pitt.edu

First Name & Middle Initial & Last Name or Official Title & Degree

Amy Boos, MSBME

amy.boos@pitt.edu

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Marco Capogrosso

Organizational Affiliation

University of Pittsburgh

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of Pittsburgh

City

Pittsburgh

State/Province

Pennsylvania

ZIP/Postal Code

15213

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Sydney Bader, MS

syb17@pitt.edu

First Name & Middle Initial & Last Name & Degree

Amy Boos, MSBME

amy.boos@pitt.edu

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

Data may be shared with other researchers for the purpose of data analysis and collaboration.

IPD Sharing Time Frame

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

IPD Sharing Access Criteria

Data must be directly requested to the PI and will be shared upon completion of necessary data sharing agreement to protect confidential patient information

Learn more about this trial

Spinal Cord Stimulation in Spinal Muscular Atrophy

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