Trial results for a study investigating the neural mechanisms of split-belt treadmill adaptation in people with Multiple Sclerosis were posted on ClinicalTrials.gov on 2025-07-03. A key finding from the analysis was that Transcutaneous Electrical Nerve Stimulation (TENS) reduced cortical activation by a mean difference of -0.078 (p=0.007) in people with multiple sclerosis when comparing TENS ON and TENS OFF conditions.
Background
Many individuals with multiple sclerosis experience challenges with balance and mobility, which can significantly increase their risk of falls. Understanding the brain activity involved in walking adaptation is crucial for developing effective rehabilitation strategies. This study aimed to explore these neural mechanisms and to assess whether nerve stimulation could enhance walking performance and adaptation in this population.
Trial design
This completed study, identified as Phase NA, enrolled 51 participants with Multiple Sclerosis. The trial's objectives included identifying the brain areas most active during walking adaptation and determining if nerve stimulation could make walking adaptation more effective. Participants engaged in split-belt treadmill training, with comparisons made between training sessions with and without Transcutaneous Electrical Nerve Stimulation (TENS).
Key results
The trial results included several key measurements and analyses:
- For Change in Cortical Activation (Unitless GLM beta weight (HbO)), the Least Squares Mean was 0.054 (Standard Error 0.021) for Split-belt Treadmill Training Without TENS, and -0.024 (Standard Error 0.021) for Split-belt Treadmill Training With TENS. Another measurement showed 0.074 (Standard Error 0.025) without TENS and -0.016 (Standard Error 0.025) with TENS.
- A Mixed Models Analysis comparing cortical activation between TENS ON and TENS OFF conditions in people with multiple sclerosis showed a Mean Difference (Net) of -0.078 (p=0.007). For healthy controls, this comparison yielded a Mean Difference (Net) of -0.089 (p=0.008).
- For Change in Adaptation Savings (Unitless Relative Step Length Asymmetry), the Least Squares Mean was 0.0032 (Standard Error 0.0103) for Split-belt Treadmill Training With TENS First, and 0.0451 (Standard Error 0.0096) for Split-belt Treadmill Training With TENS Second. Other measurements showed 0.0221 (Standard Error 0.0124) with TENS First and 0.0278 (Standard Error 0.0112) with TENS Second.
- A Mixed Models Analysis comparing adaptation savings between TENS ON and TENS OFF conditions in people with multiple sclerosis showed a Mean Difference (Net) of 0.042 (p=0.014). For healthy controls, this comparison showed a Mean Difference (Net) of -0.0058 (p=0.878).
- For Rate of Step Length Asymmetry Adaptation (Unitless Relative Step Length Asymmetry), the Least Squares Mean was -0.090 (Standard Error 0.012) for Split-belt Treadmill Training Without TENS, and -0.088 (Standard Error 0.013) for Split-belt Treadmill Training With TENS. Another measurement showed -0.095 (Standard Error 0.014) without TENS and -0.103 (Standard Error 0.016) with TENS.
- A Mixed Models Analysis comparing the rate of adaptation between TENS ON and TENS OFF conditions in people with multiple sclerosis showed a Mean Difference (Final Values) of 0.002 (p=0.898). For healthy controls, this comparison showed a Mean Difference (Final Values) of -0.008 (p=0.698).
What this means
The posted results suggest that Transcutaneous Electrical Nerve Stimulation (TENS) can significantly reduce cortical activation during walking adaptation in both people with multiple sclerosis (p=0.007) and healthy controls (p=0.008). Furthermore, in individuals with multiple sclerosis, TENS was associated with a significant increase in adaptation savings (p=0.014). These findings indicate that TENS may be a valuable tool to modulate brain activity and improve motor learning, potentially enhancing the effectiveness of walking rehabilitation programs for patients with multiple sclerosis. The lack of significant difference in the rate of adaptation suggests that TENS primarily impacts the efficiency of learning and neural effort rather than the speed of initial adaptation.
Source
The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for the study NCT05878873, titled "The Neural Mechanisms of Split-belt Treadmill Adaptation in People With Multiple Sclerosis", were posted on 2025-07-03 on clinicaltrials.gov.