Testosterone and Long-Pulse-Width Stimulation (TLPS) on Denervated Muscles and Cardio-Metabolic Risk Factors After Spinal Cord Injury: A Pilot Randomized Trial.

Compliance and adherence were greater in the TT + NMES group compared to the TT + LPWS group.

• Ten SCI participants with chronic lower motor neuron injury were randomized into either TT + LPWS (n = 5) or TT + NMES (n = 5).
• Stimulation was applied twice weekly for 12 months in both groups.
• The TT + LPWS group had lower compliance rates, suggesting practical challenges with the intervention.

There was a 25% increase in rectus femoris muscle cross-sectional area (CSA) following the 6-month measurement in the TT + LPWS group.

• Muscle size was assessed using magnetic resonance imaging (MRI).
• The 25% increase in RF muscle CSA was observed at post-intervention 1 (P1), corresponding to 6 months of training.
• Effects on muscle size were described as 'modest between groups' overall.
• Long pulse width stimulation parameters were 120–150 ms.

There was a recognizable but non-significant decrease in intramuscular fat in both groups.

• Intramuscular fat changes were observed in both the TT + LPWS and TT + NMES groups.
• The decrease did not reach statistical significance.
• Body composition was assessed using both MRI and dual x-ray absorptiometry (DXA).

There was a trend toward decreased trunk fat mass following TT + LPWS.

• The trend for decrease in trunk fat mass in the TT + LPWS group had a p-value of 0.07.
• An interaction in android lean mass between groups was statistically significant (p = 0.037).
• These measurements were conducted using DXA.

There was a trend in mean differences in DXA-visceral adipose tissue (VAT) between groups at the 6-month measurement.

• The trend in DXA-VAT between groups at P1 measurements had a p-value of 0.08.
• Metabolic profile assessment also encompassed measurements of resting metabolic rate and carbohydrate and lipid profiles.
• The finding did not reach conventional statistical significance.

TT + LPWS showed a trending decline in MURF1 and FOXO3 gene expression, with levels returning toward those seen in the TT + NMES group before 12 months.

• MURF1 and FOXO3 are genes targeting muscle atrophy pathways.
• The decline was described as a 'trending' change, not reaching statistical significance.
• Gene expression was measured from muscle biopsies analyzing RNA signaling pathways.
• Signaling pathway analysis suggested downregulation of genes involved in muscle atrophy pathways in the TT + LPWS group.

The pilot data demonstrated the safety of applying long pulse width stimulation in persons with spinal cord injury.

• Participants had chronic lower motor neuron injury.
• Measurements were conducted at baseline (week 0), 6 months (post-intervention 1), and one week following 12 months of training (post-intervention 2).
• No adverse safety events precluded continuation of the study, supporting feasibility of the approach.

Mitochondrial oxidative phosphorylation was assessed via muscle biopsy as part of the outcome measures.

• Muscle biopsies were captured to measure RNA signaling pathways and mitochondrial oxidative phosphorylation.
• The study hypothesized that combined TT + LPWS would increase mitochondrial health in SCI persons with lower motor neuron injury.
• Both upregulation of hypertrophy gene expression and downregulation of atrophy gene expression were hypothesized outcomes.