Testing Pulse Stimulation to Improve Motor Function in People With ALS: A Pilot Study

NCT06681610 | Recruiting

• 2 other identifiers: NEU-TPS-ALS-01FUSF-RAP-S-23-00096
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

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

Conditions

Amyotrophic Lateral Sclerosis (ALS)

Keywords

Transcranial Pulse Stimulation (TPS); Amyotrophic Lateral Sclerosis (ALS)

Outcome Measures

Primary Outcomes (2)

• 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

  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.

  baseline to week 24

Secondary Outcomes (8)

• 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

• Differences (treated vs sham) and change in plasma NfL levels

  baseline to month 6

Other Outcomes (7)

• Change in biomarker SOD1 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 C9orf72 Levels in nEVs from Plasma

  baseline to week 4 and 8

Study Arms (2)

TPS

EXPERIMENTAL

The stimulation will be 20 min duration as indicated in the CE mark approval. Each session involves 6,000 pulses in the hand region of the motor cortex with 3,000 on each side of the brain. The system uses a low energy flux density maximum of 0.25 mJ/mm2 accordingly with EMA and FDA guidelines (high energy is defined as \> 0.5 mJ/mm2). The standard therapy involves 6 sessions in 2 weeks as indicated in the CE mark.

Device: Transcranial Pulse Stimulation

sham

SHAM COMPARATOR

The transcranial pulse stimulation with the same device and the same protocol uses a membrane on the device that blocks the sound waves. Participants' motor cortex is not stimulated.

Device: Transcranial Pulse Stimulation

Interventions

Transcranial Pulse Stimulation DEVICE

low intensity shock-waves stimulation of the motor cortex, bilateral

TPS; sham

Eligibility Criteria

• Age: 21 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• to 80 years old and male or female

You may not qualify if:

• patients with fALS (based on medical history) that are unable to tolerate TMS and MRI studies or have a contraindication as described below

Sponsors & Collaborators

• Parc de Salut Mar: lead

Study Sites (1)

Hospital del Mar

Barcelona, Catalonia, 08003, Spain

RECRUITING

Related Publications (3)

• 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.

  PMID: 29396478 BACKGROUND

• 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.

  PMID: 34588588 BACKGROUND

• 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.

  PMID: 36116464 BACKGROUND

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis

Interventions

Transcranial Magnetic Stimulation

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Magnetic Field Therapy; Therapeutics

Central Study Contacts

Alba Leon, MD

CONTACT

+34932 48 30 00; aleonjorba@psmar.cat

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: randomised, double blind, sham controlled clinical study

Study Record Dates

• First Submitted: November 6, 2024
• First Posted: November 8, 2024
• Study Start: October 24, 2024
• Primary Completion: April 1, 2025
• Study Completion (Estimated): December 1, 2026
• Last Updated: November 8, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Access Criteria: protocol will be published as supplementary material. SAP and ICF will be provided upon reasonable request

Locations

ES (1)