Non-Invasive Stimulation for Improving Motor Function

NCT03592173 | Active Not Recruiting Phase 2 FDA Device

• 1 other identifier: BRC391
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine if spinal excitability is increased with a Spinal Associative Stimulation (SAS) protocol, and to determine the functional consequences of this technique on motor recovery.

Conditions

Spinal Cord Injuries

Outcome Measures

Primary Outcomes (1)

• Change in H-Reflex Threshold

  Assessment of muscle reaction after stimulation of sensory fibers

  Baseline compared with immediately after intervention

Secondary Outcomes (6)

• Lower Extremity Motor Score (LEMS)

  Baseline, immediately after intervention

• Walking Index for Spinal Cord Injury (WISCI II)

  Baseline, immediately after intervention

• 10 Meter Walk Test

  Baseline, immediately after intervention

• Spinal Cord Independence Measure, Version 3 (SCIM III)

  Baseline, immediately after intervention

• Muscle Force

  Baseline, immediately after intervention

Study Arms (3)

SAS20

EXPERIMENTAL

The paired stimulation (SAS) will be comprised of patient adjusted subthreshold TMS (80% of resting motor threshold over optimal site for soleus muscle), delivered 20ms prior to a peripheral nerve stimulus in the popliteal fossa and will be repeated at 0.1 Hz for 15 minutes (90 stimuli pairs).

Diagnostic Test: Paired TMS & Peripheral Nerve Stimulation

SAS0

ACTIVE COMPARATOR

The paired stimulation (SAS) will be comprised of patient adjusted subthreshold TMS (80% of resting motor threshold over optimal site for soleus muscle), delivered 0ms prior to a peripheral nerve stimulus in the popliteal fossa and will be repeated at 0.1 Hz for 15 minutes (90 stimuli pairs).

Diagnostic Test: Paired TMS & Peripheral Nerve Stimulation

SAS50

ACTIVE COMPARATOR

The paired stimulation (SAS) will be comprised of patient adjusted subthreshold TMS (80% of resting motor threshold over optimal site for soleus muscle), delivered 50ms prior to a peripheral nerve stimulus in the popliteal fossa and will be repeated at 0.1 Hz for 15 minutes (90 stimuli pairs).

Diagnostic Test: Paired TMS & Peripheral Nerve Stimulation

Interventions

Paired TMS & Peripheral Nerve Stimulation DIAGNOSTIC_TEST

Method of assessing neurophysiology and activity of the spinal cord

SAS0; SAS20; SAS50

Eligibility Criteria

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

You may qualify if:

• Spinal cord injury subjects with chronic lesions (\> 6 months after the injury)
• Motor incomplete lesion, measured by the American Spinal cord Injury Association (ASIA) Impairment Scale (AIS)
• Traumatic cause of lesion; d) Some degree of motor function in the ankle flexor and extensors (Low extremity Motor Score - LEMS≥3).

You may not qualify if:

• Motor and sensory complete lesion (AIS A); LEMS \< 3;
• Non-traumatic cause of lesion
• Medically unstable condition
• Other concurrent neurological illness
• Presence of a potential TMS risk factor (detailed below)
• Potential TMS risk factor:
• Damaged skin at the site of stimulation
• Presence of an electrically, magnetically or mechanically activated implant
• An intracerebral vascular clip, or any other electrically sensitive support system
• Metal in any part of the body, including metal injury to the eye
• A history of medication-resistant epilepsy in the family
• Past history of seizures or unexplained spells of loss of consciousness.

Sponsors & Collaborators

• Kathleen Friel: lead
• Burke Medical Research Institute: collaborator

Study Sites (1)

Burke Medical Research Institute

White Plains, New York, 10605, United States

Location

Related Publications (14)

• Pascual-Leone A. Disrupting the brain to guide plasticity and improve behavior. Prog Brain Res. 2006;157:315-329. doi: 10.1016/s0079-6123(06)57019-0.

  PMID: 17167918 BACKGROUND

• Deletis V, Schild JH, Beric A, Dimitrijevic MR. Facilitation of motor evoked potentials by somatosensory afferent stimulation. Electroencephalogr Clin Neurophysiol. 1992 Oct;85(5):302-10. doi: 10.1016/0168-5597(92)90106-l.

  PMID: 1385090 BACKGROUND

• Hiersemenzel LP, Curt A, Dietz V. From spinal shock to spasticity: neuronal adaptations to a spinal cord injury. Neurology. 2000 Apr 25;54(8):1574-82. doi: 10.1212/wnl.54.8.1574.

  PMID: 10762496 BACKGROUND

• Kumru H, Vidal J, Kofler M, Benito J, Garcia A, Valls-Sole J. Exaggerated auditory startle responses in patients with spinal cord injury. J Neurol. 2008 May;255(5):703-9. doi: 10.1007/s00415-008-0780-3. Epub 2008 Feb 21.

  PMID: 18286318 BACKGROUND

• Rothwell JC. Techniques and mechanisms of action of transcranial stimulation of the human motor cortex. J Neurosci Methods. 1997 Jun 27;74(2):113-22. doi: 10.1016/s0165-0270(97)02242-5.

  PMID: 9219881 BACKGROUND

• Kofler M, Valls-Sole J, Fuhr P, Schindler C, Zaccaria BR, Saltuari L. Sensory modulation of voluntary and TMS-induced activation in hand muscles. Exp Brain Res. 2008 Jul;188(3):399-409. doi: 10.1007/s00221-008-1372-2. Epub 2008 Apr 18.

  PMID: 18421450 BACKGROUND

• Pascual-Leone A, Tarazona F, Keenan J, Tormos JM, Hamilton R, Catala MD. Transcranial magnetic stimulation and neuroplasticity. Neuropsychologia. 1999 Feb;37(2):207-17. doi: 10.1016/s0028-3932(98)00095-5.

  PMID: 10080378 BACKGROUND

• Serranova T, Valls-Sole J, Munoz E, Genis D, Jech R, Seeman P. Abnormal corticospinal tract modulation of the soleus H reflex in patients with pure spastic paraparesis. Neurosci Lett. 2008 May 23;437(1):15-9. doi: 10.1016/j.neulet.2008.03.068. Epub 2008 Mar 28.

  PMID: 18434014 BACKGROUND

• Boorman G, Becker WJ, Morrice BL, Lee RG. Modulation of the soleus H-reflex during pedalling in normal humans and in patients with spinal spasticity. J Neurol Neurosurg Psychiatry. 1992 Dec;55(12):1150-6. doi: 10.1136/jnnp.55.12.1150.

  PMID: 1479394 BACKGROUND

• Poon DE, Roy FD, Gorassini MA, Stein RB. Interaction of paired cortical and peripheral nerve stimulation on human motor neurons. Exp Brain Res. 2008 Jun;188(1):13-21. doi: 10.1007/s00221-008-1334-8. Epub 2008 Mar 11.

  PMID: 18330548 BACKGROUND

• Stefan K, Kunesch E, Benecke R, Cohen LG, Classen J. Mechanisms of enhancement of human motor cortex excitability induced by interventional paired associative stimulation. J Physiol. 2002 Sep 1;543(Pt 2):699-708. doi: 10.1113/jphysiol.2002.023317.

  PMID: 12205201 BACKGROUND

• Ridding MC, McKay DR, Thompson PD, Miles TS. Changes in corticomotor representations induced by prolonged peripheral nerve stimulation in humans. Clin Neurophysiol. 2001 Aug;112(8):1461-9. doi: 10.1016/s1388-2457(01)00592-2.

  PMID: 11459686 BACKGROUND

• Valls-Sole J, Alvarez R, Tolosa ES. Responses of the soleus muscle to transcranial magnetic stimulation. Electroencephalogr Clin Neurophysiol. 1994 Dec;93(6):421-7. doi: 10.1016/0168-5597(94)90148-1.

  PMID: 7529691 BACKGROUND

• Hoffken O, Veit M, Knossalla F, Lissek S, Bliem B, Ragert P, Dinse HR, Tegenthoff M. Sustained increase of somatosensory cortex excitability by tactile coactivation studied by paired median nerve stimulation in humans correlates with perceptual gain. J Physiol. 2007 Oct 15;584(Pt 2):463-71. doi: 10.1113/jphysiol.2007.140079. Epub 2007 Aug 16.

  PMID: 17702814 BACKGROUND

MeSH Terms

Conditions

Spinal Cord Injuries

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Trauma, Nervous System; Wounds and Injuries

Study Officials

• Kathleen Friel, PhD

  Burke Medical Research Institute

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Laboratory Director

Model Details: Thirty chronic SCI participants will given the SAS intervention and a control intervention in a randomized cross-over study, with at least one week between interventions. Each patient will be required to attend the Burke Medical Research Institute on three occasions. We will use a within-subjects design, to test changes in neurophysiologic and voluntary measures after intervention with respect to baseline.

Study Record Dates

• First Submitted: May 16, 2018
• First Posted: July 19, 2018
• Study Start: July 1, 2013
• Primary Completion: September 1, 2025
• Study Completion: December 1, 2025
• Last Updated: August 6, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)