Clinical trial NCT05430113: Spinal Cord Stimulation in Spinal Muscular Atrophy
Official title: Spinal Cord Stimulation for the Treatment of Motor Deficits in People With Spinal Muscular Atrophy
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Spinal Muscular Atrophy Type 3
Spinal Muscular Atrophy Type 4
Keywords: Spinal Muscular Atrophy
Spinal Cord Stimulation
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
Collaborators: name: Roche-Genentech
First posted: 2022-06-24
Enrollment: 3
Sex: ALL
Minimum age (years): 16
Maximum age (years): 64
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention 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.
Primary purpose: BASIC_SCIENCE

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.

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

Primary outcomes:
measure: Muscle Weakness
timeFrame: 29 days
measure: Number and Severity of Adverse Events
timeFrame: 29 days
Secondary outcomes:
measure: Muscle Weakness 2
timeFrame: 29 days
measure: Motor Function ROM
timeFrame: 29 days
measure: Motor Function: 6-Minute Walk Teset
timeFrame: 29 days
measure: Motor Function RHS
timeFrame: 29 days
measure: Motor Function: Fatigue
timeFrame: 29 days
measure: Discomfort/Pain
timeFrame: 29 days
measure: Sensorimotor Network Structure Density
timeFrame: 29 days
measure: Impression
timeFrame: 29 days
measure: Sensorimotor Network Structure Integrity
timeFrame: 29 days
measure: Sensorimotor Network Function
timeFrame: 29 days
measure: Cortico-spinal Tract Integrity
timeFrame: 29 days
measure: Spinal Circuit Excitability
timeFrame: 29 days
measure: Motoneuron Firing Rates
timeFrame: 29 days
measure: Motor Firing Number
timeFrame: 29 days
Other outcomes:
Locations:
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
Study officials:
affiliation: University of Pittsburgh
name: Marco Capogrosso
role: PRINCIPAL_INVESTIGATOR
References: