Spinal Cord Stimulation in Spinal Muscular Atrophy

NCT ID: NCT05430113

Last Updated: 2025-05-16

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 3 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-04-05
• Study Completion Date: 2027-08-31

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.

Conditions

Spinal Muscular Atrophy Type 3; Spinal Muscular Atrophy Type 4

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Spinal Cord Stimulator (octopolar Medtronic Vectris Leads)

Intervention Type: DEVICE

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

Interventions

Spinal Cord Stimulator (octopolar Medtronic Vectris Leads)

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

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

1. 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.

2. Subject has a diagnosis of 5q-autosomal recessive SMA confirmed by determination of a genetic deletion in the SMN1 gene (5q12.2-q13.3)

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

4. Subject is ≥16 years of age and < 65 years of age

5. Subject is able to stand independently for ≥3 seconds

6. RHS score lower or equal to 65

7. 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

1. Subject has deformation of the spinal canal preventing lead implantation as judged by the study neurosurgeon

2. Subject has size of spinal canal that is insufficient for lead implantation as judged by the study neurosurgeon

3. Subject has moderate or severe joint contractures that would affect ability to perform study measures

4. Subject has severe behavioral or cognitive problems that preclude participation in the study, in the opinion of the investigator

5. 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

6. Female subjects are pregnant or breastfeeding

7. Subject has severe claustrophobia

8. 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

9. Subject has medical implant that precludes magnetic resonance imaging

• Minimum Eligible Age: 16 Years
• Maximum Eligible Age: 64 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Roche-Genentech

INDUSTRY

Sponsor Role: collaborator

Marco Capogrosso

OTHER

Sponsor Role: lead

Responsible Party

Marco Capogrosso

Assistant Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Marco Capogrosso

Role: PRINCIPAL_INVESTIGATOR

University of Pittsburgh

Locations

University of Pittsburgh

Pittsburgh, Pennsylvania, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 39910271 (View on PubMed)

Other Identifiers

STUDY21080158

Identifier Type: -

Identifier Source: org_study_id