Clinical trial NCT06681610: Testing Pulse Stimulation to Improve Motor Function in People With ALS: A Pilot Study
Official title: Modulation of the Motor Pathway by Transcranial Pulse Stimulation in People With ALS: a Pilot Randomized Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Amyotrophic Lateral Sclerosis (ALS)
Keywords: Transcranial Pulse Stimulation (TPS)
Amyotrophic Lateral Sclerosis (ALS)
Lead sponsor: Parc de Salut Mar
Sponsor class: OTHER
First posted: 2024-11-08
Enrollment: 50
Sex: ALL
Minimum age (years): 21
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: randomised, double blind, sham controlled clinical study
Primary purpose: TREATMENT

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


Eligibility criteria: 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

Primary outcomes:
measure: Change in the short intracortical inhibition (SICI) of the motor cortex from baseline to week 8.
timeFrame: baseline to week 8
measure: Change from baseline to month 6 in the ALS functional rating scale-revised (ALSFRS-R) total score
timeFrame: baseline to week 24
Secondary outcomes:
measure: Change plasma neurofilament light chain (NfL) levels
timeFrame: baseline to week 4 and 8
measure: Changes in muscle strength, assessed by the Medical Research Council (MRC) sum score
timeFrame: baseline to week 4 and 8
measure: Changes in hand-held dynamometry
timeFrame: baseline to week 8
measure: Differences (treated vs sham) and change in the slow vital capacity (SVC)
timeFrame: from baseline to month 6
measure: Differences (treated vs sham) and change in plasma NfL levels
timeFrame: baseline to month 6
measure: Change in Motor Evoked Potential (MEP) Amplitudes
timeFrame: baseline to week 4 and 8
measure: Change in Resting Motor Threshold
timeFrame: baseline to week 4 and 8
measure: Change in Intra-Cortical Facilitation
timeFrame: baseline to week 4 and 8
Other outcomes:
measure: Change in biomarker SOD1 Levels in nEVs from Plasma
timeFrame: baseline to week 4 and 8
measure: Change in biomarker Ataxin 2 Levels in nEVs from Plasma
timeFrame: baseline to week 4 and 8
measure: Change in biomarker C9orf72 Levels in nEVs from Plasma
timeFrame: baseline to week 4 and 8
measure: Change in biomarker UNC13A Levels in nEVs from Plasma
timeFrame: baseline to week 4 and 8
measure: Change in biomarker TDP43 Levels in nEVs from Plasma
timeFrame: baseline to week 4 and 8
measure: Change in biomarker Stathmin 2 Levels in nEVs from Plasma
timeFrame: baseline to week 4 and 8
measure: Change in NfH Levels in nEVs from Plasma
timeFrame: baseline to week 4 and 8
Locations:
city: Barcelona
country: Spain
facility: Hospital del Mar
state: Catalonia
Study officials:
References:
citation: Voroslakos M, Takeuchi Y, Brinyiczki K, Zombori T, Oliva A, Fernandez-Ruiz A, Kozak G, Kincses ZT, Ivanyi B, Buzsaki G, Berenyi A. Direct effects of transcranial electric stimulation on brain circuits in rats and humans. Nat Commun. 2018 Feb 2;9(1):483. doi: 10.1038/s41467-018-02928-3.
citation: Kim HC, Lee W, Kunes J, Yoon K, Lee JE, Foley L, Kowsari K, Yoo SS. Transcranial focused ultrasound modulates cortical and thalamic motor activity in awake sheep. Sci Rep. 2021 Sep 29;11(1):19274. doi: 10.1038/s41598-021-98920-x.
citation: Feldman EL, Goutman SA, Petri S, Mazzini L, Savelieff MG, Shaw PJ, Sobue G. Amyotrophic lateral sclerosis. Lancet. 2022 Oct 15;400(10360):1363-1380. doi: 10.1016/S0140-6736(22)01272-7. Epub 2022 Sep 15.