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| ID | Type | Description | Link |
|---|---|---|---|
| FUSF-RAP-S-23-00096 | Other Grant/Funding Number | Focused Ultrasound Foundation and ALS Foundation. USA |
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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:
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:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Transcranial Pulse Stimulation | Device | low intensity shock-waves stimulation of the motor cortex, bilateral |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Alba Leon, MD | Contact | +34932 48 30 00 | aleonjorba@psmar.cat |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hospital del Mar | Recruiting | Barcelona | Catalonia | 08003 | Spain |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 29396478 | Background | 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. | |
| 34588588 | Background |
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we will provide access to protocol, SAP and ICF
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protocol will be published as supplementary material. SAP and ICF will be provided upon reasonable request
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jul 4, 2024 | Nov 5, 2024 | Prot_000.pdf |
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| ID | Term |
|---|---|
| D000690 | Amyotrophic Lateral Sclerosis |
| ID | Term |
|---|---|
| D013118 | Spinal Cord Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D016472 | Motor Neuron Disease |
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| ID | Term |
|---|---|
| D050781 | Transcranial Magnetic Stimulation |
| ID | Term |
|---|---|
| D055909 | Magnetic Field Therapy |
| D013812 | Therapeutics |
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randomised, double blind, sham controlled clinical study
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| 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 | Candidate biomarkers are: SOD1, Ataxin 2, C90rf72, UNC13A, TDP43, stathmin 2, NfL and NfH levels | baseline to month 6 |
| Change in Motor Evoked Potential (MEP) Amplitudes | ppTMS will be used to assess changes in motor cortex excitability via MEP amplitude (measured in millivolts) | baseline to week 4 and 8 |
| Change in Resting Motor Threshold | RMT will be recorded to assess baseline motor cortex excitability (measured as a percentage of maximum stimulator output) | baseline to week 4 and 8 |
| Change in Intra-Cortical Facilitation | ICF will be measured to assess synaptic excitability | baseline to week 4 and 8 |
| baseline to week 4 and 8 |
| 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 |
| 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. |
| 36116464 | 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. |
| D019636 | Neurodegenerative Diseases |
| D057177 | TDP-43 Proteinopathies |
| D009468 | Neuromuscular Diseases |
| D057165 | Proteostasis Deficiencies |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |