Spinal Cord Associative Plasticity for ALS

NCT06172621 | Recruiting

• 2 other identifiers: B4258-R1I01RX004258
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

Veterans are at higher risk than non-Veterans of falling ill with amyotrophic lateral sclerosis (ALS). The investigators have shown that synchronized stimulation over the brain and cervical spinal cord can temporarily strengthen weakened nerve circuits between the brain and hand muscles in people with ALS. The current proposal will take the next step of individualizing this intervention, then applying it repetitively in an attempt to achieve direct clinical benefit on hand strength and function. Following an initial 2-3 month period of optimizing the intervention for each individual, the investigators will compare the effects of two-week programs of paired brain-spinal stimulation with or without hand exercises.

Conditions

Amyotrophic Lateral Sclerosis

Keywords

neuromodulation; spinal cord stimulation; task-oriented exercise; transcranial magnetic stimulation

Outcome Measures

Primary Outcomes (2)

• Amplitude of intrinsic hand muscle response to single-pulse transcranial magnetic stimulation (TMS)

  The primary neurophysiological outcome will be corticospinal excitability measured at the first dorsal interosseous (FDI) muscle. If no suitable FDI muscle, will substitute with abductor pollicis brevis (APB) muscle.

  Through study completion, up to 6 months

• Hand dexterity on the nine-hole peg test

  Time to complete placement of nine pegs into their respective holes using the target hand.

  Through study completion, up to 6 months

Secondary Outcomes (3)

• Volitional strength assessed by isometric dynamometry (key-pinch configuration)

  Through study completion, up to 6 months

• Volitional strength assessed by isometric dynamometry (tip-to-tip configuration)

  Through study completion, up to 6 months

• Volitional strength assessed by isometric dynamometry (grip configuration)

  Through study completion, up to 6 months

Study Arms (2)

SCAP alone

ACTIVE COMPARATOR

After a run-in phase of 2-4 months to determine individualized stimulation parameters, participants will be randomized into a comparator group of two weeks (6 sessions) of SCAP intervention alone.

Procedure: Spinal Cord Associative Plasticity (SCAP)

SCAP plus task-oriented exercise

EXPERIMENTAL

After a run-in phase of 2-4 months to determine individualized stimulation parameters, participants will be randomized into a comparator group of two weeks (6 sessions) of SCAP intervention plus upper extremity task-oriented exercise.

Procedure: Spinal Cord Associative Plasticity (SCAP); Procedure: Upper extremity task-oriented exercise

Interventions

Spinal Cord Associative Plasticity (SCAP) PROCEDURE

Paired non-invasive brain and spinal cord stimulation.

SCAP alone; SCAP plus task-oriented exercise

Upper extremity task-oriented exercise PROCEDURE

Participants will perform a range of exercises composed of tasks resembling daily home/community activities such as stacking and sorting small objects, manipulating writing utensils, keys, buttons, etc.

SCAP plus task-oriented exercise

Eligibility Criteria

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

You may qualify if:

• Diagnosis of ALS by Gold Coast Criteria (Shefner et al. 2020) or "definite" or "probable" ALS by revised El Escorial Criteria (Brooks et al. 2000)
• Incomplete weakness: Score of 1, 2, 3, or 4 (out of 5) on manual muscle testing of finger extension, finger flexion, or finger abduction in left or right hand
• TSCS-evoked potential amplitude of at least 25 V in left or right abductor pollicis brevis (APB) or first dorsal interosseous (FDI) muscles with a resting motor threshold of 55 mA or lower
• TMS-evoked potential amplitude of at least 25 V in left or right abductor pollicis brevis (APB) or first dorsal interosseous (FDI) muscles with a resting motor threshold of 65% MSO or lower

You may not qualify if:

• History of seizures
• Ventilator dependence or patent tracheostomy site
• Use of medications that significantly lower seizure threshold, such as amphetamines and dalfampridine
• History of severe head trauma (evidence of brain contusion or hemorrhage or depressed skull fracture on prior imaging)
• History of implanted brain/spine/nerve stimulators, aneurysm clips, ferromagnetic metallic implants in the head (except for inside mouth); cochlear implants; cardiac pacemaker/defibrillator; intracardiac lines; currently increased intracranial pressure; or other contraindications to brain or spine stimulation
• Significant coronary artery or cardiac conduction disease; heart failure with an ejection fraction of less than 30% or with a New York Heart Association Functional Classification of Class III or IV
• History of significant tinnitus
• History of bipolar disorder
• History of suicide attempt
• Active psychosis
• Ongoing illicit drug or alcohol abuse in the past 6 months
• Heavy alcohol consumption (greater than equivalent of 5 ounces of liquor) within previous 48 hours
• Open skin lesions over the neck, shoulders, or arm stimulation or recording sites
• Pregnancy

Sponsors & Collaborators

• VA Office of Research and Development: lead

Study Sites (1)

James J. Peters VA Medical Center, Bronx, NY

The Bronx, New York, 10468-3904, United States

RECRUITING

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis

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

Study Officials

• Noam Y. Harel, MD PhD

  James J. Peters Veterans Affairs Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Francisco E Castano, MPH

CONTACT

(718) 584-9000; francisco.castano@va.gov

Noam Y Harel, MD PhD

CONTACT

(718) 584-9000; Noam.Harel@va.gov

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Model Details: After a run-in phase of 2-4 months to determine individualized stimulation parameters, participants will be randomized into Group A and Group B. Group A will undergo 2 weeks (6 sessions) of SCAP alone. Group B will undergo 2 weeks (6 sessions) of SCAP plus upper extremity task-oriented exercise.

Study Record Dates

• First Submitted: December 6, 2023
• First Posted: December 15, 2023
• Study Start: April 1, 2024
• Primary Completion (Estimated): November 30, 2027
• Study Completion (Estimated): February 29, 2028
• Last Updated: March 20, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Within 1 year after study completion.
• Access Criteria: Permanent

Locations

US (1)