Amyotrophic Lateral Sclerosis (ALS)
Conditions
Keywords
Transcranial Pulse Stimulation (TPS), Amyotrophic Lateral Sclerosis (ALS)
Brief summary
The goal of this clinical trial is to assess the efficacy of TPS of the motor cortex on biomarkers and clinical endpoints in patients with ALS. The main questions it aims to answer are: * Stage 1: Is there a change in the short intracortical inhibition (SICI) of the motor cortex from baseline to week 8? * Stage 2: Is there a change from baseline to month 6 in the ALS functional rating scale-revised (ALSFRS-R) total score? In stage 2, researchers will compare the group receiving the stimulation vs the group receiving a sham stimulation to see if there is a difference in motor cortex activity and in the ALSFRS-R score Participants will receive either: * the TPS treatment * a sham TPS treatment
Interventions
low intensity shock-waves stimulation of the motor cortex, bilateral
Sponsors
Parc de Salut Mar
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Intervention model description
randomised, double blind, sham controlled clinical study
Eligibility
Sex/Gender
ALL
Age
21 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Patients with diagnosis of sporadic ALS (definite or clinically probable) as defined by the World Federation of Neurology revised El Escorial criteria * SVC of 50% or greater of estimated measure and presence of measurable motor evoked potential * 21 to 80 years old and male or female
Exclusion criteria
* patients with fALS (based on medical history) that are unable to tolerate TMS and MRI studies or have a contraindication as described below
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in the short intracortical inhibition (SICI) of the motor cortex from baseline to week 8. | baseline to week 8 | — |
| Change from baseline to month 6 in the ALS functional rating scale-revised (ALSFRS-R) total score | baseline to week 24 | The ALS Functional Rating Scale-Revised Each function is scored from 4 (normal) to 0 (no ability), with a maximum total score of 48 and a minimum total score of 0. Higher scores mean a better outcome. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Motor Evoked Potential (MEP) Amplitudes | baseline to week 4 and 8 | ppTMS will be used to assess changes in motor cortex excitability via MEP amplitude (measured in millivolts) |
| Differences (treated vs sham) and change in plasma NfL levels | baseline to month 6 | Candidate biomarkers are: SOD1, Ataxin 2, C90rf72, UNC13A, TDP43, stathmin 2, NfL and NfH levels |
| Change in Resting Motor Threshold | baseline to week 4 and 8 | RMT will be recorded to assess baseline motor cortex excitability (measured as a percentage of maximum stimulator output) |
| Change in Intra-Cortical Facilitation | baseline to week 4 and 8 | ICF will be measured to assess synaptic excitability |
| Change plasma neurofilament light chain (NfL) levels | baseline to week 4 and 8 | — |
| Changes in muscle strength, assessed by the Medical Research Council (MRC) sum score | baseline to week 4 and 8 | — |
| Changes in hand-held dynamometry | baseline to week 8 | — |
| Differences (treated vs sham) and change in the slow vital capacity (SVC) | from baseline to month 6 | — |
Other
| Measure | Time frame |
|---|---|
| Change in biomarker UNC13A Levels in nEVs from Plasma | baseline to week 4 and 8 |
| Change in biomarker TDP43 Levels in nEVs from Plasma | baseline to week 4 and 8 |
| Change in biomarker Stathmin 2 Levels in nEVs from Plasma | baseline to week 4 and 8 |
| Change in NfH Levels in nEVs from Plasma | baseline to week 4 and 8 |
| Change in biomarker Ataxin 2 Levels in nEVs from Plasma | baseline to week 4 and 8 |
| Change in biomarker SOD1 Levels in nEVs from Plasma | baseline to week 4 and 8 |
| Change in biomarker C9orf72 Levels in nEVs from Plasma | baseline to week 4 and 8 |
Countries
Spain
Contacts
Primary ContactAlba Leon, MD
Outcome results
None listed