Trial Outcomes & Findings for Spinal Cord Stimulation in Spinal Muscular Atrophy (NCT NCT05430113)

Population: 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.

Population: 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.

Population: 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);

Population: 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.

Population: 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.

Population: 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.

Population: We report the number of participants who reported discomfort/pain ≥ 3/10 on the 1-10 scale

Population: 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.

Population: 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.

Population: 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.

Population: 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.

Population: 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).

Population: 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)

Population: 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.

Population: 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