Non-Invasive Stimulation for Improving Motor Function

NCT ID: NCT03592173

Last Updated: 2024-08-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE2

Total Enrollment

30 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-07-31

Study Completion Date

2025-12-31

Brief Summary

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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.

Detailed Description

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Recovery of motor function continues to be a problem following Spinal Cord Injury. Non-invasive brain stimulation techniques, targeting cortical areas, have been shown to enhance the excitability in the human motor cortex, and these changes in the motor cortex may be of significance for the rehabilitation of brain injured patients. However, little is known about the adaptational changes in the excitability/plasticity of spinal neural circuits in spinal cord injury patients.

The purpose of this study is to investigate the excitability of cortical and spinal inhibitory and excitatory mechanisms before and following a period of repetitive and synchronized dual peripheral nerve and brain stimulation. Repetitive, paired brain and peripheral nerve stimulation as a neuromodulatory tool, paired associative stimulation (PAS), has been well described. In this technique, stimuli are timed such that afferent and efferent volleys interact at the level of the cortex, that lead to a temporary enhancement of Motor Evoked Potential (MEP) amplitude in target muscles, and when applied repeatedly, lead to a sustained effect, outlasting the intervention period. This repetitive technique has been done in healthy subjects and patients with neurological diseases. By modifying the time between paired stimuli, the investigators will generate afferent/efferent interactions in the spinal cord.

The working hypothesis of this study is that the acute facilitation of the H-reflex during Paired TMS and peripheral nerve stimulation, may be harnessed to modulate spinal excitability (sustained increase in the MEP amplitude). That is, the investigators will test if similar to PAS, a change in excitability outlasting the stimulation/intervention period may occur with afferent/efferent interactions, although at the level of the spinal cord rather than the cortex, and be useful to strengthen residual pathways after damage to the spinal cord.

Conditions

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Spinal Cord Injuries

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

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.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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SAS20

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).

Group Type EXPERIMENTAL

Paired TMS & Peripheral Nerve Stimulation

Intervention Type DIAGNOSTIC_TEST

Method of assessing neurophysiology and activity of the spinal cord

SAS0

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).

Group Type ACTIVE_COMPARATOR

Paired TMS & Peripheral Nerve Stimulation

Intervention Type DIAGNOSTIC_TEST

Method of assessing neurophysiology and activity of the spinal cord

SAS50

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).

Group Type ACTIVE_COMPARATOR

Paired TMS & Peripheral Nerve Stimulation

Intervention Type DIAGNOSTIC_TEST

Method of assessing neurophysiology and activity of the spinal cord

Interventions

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Paired TMS & Peripheral Nerve Stimulation

Method of assessing neurophysiology and activity of the spinal cord

Intervention Type DIAGNOSTIC_TEST

Eligibility Criteria

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Inclusion Criteria

* 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).

Exclusion Criteria

* 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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Burke Medical Research Institute

OTHER

Sponsor Role collaborator

Kathleen Friel

OTHER

Sponsor Role lead

Responsible Party

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Kathleen Friel

Laboratory Director

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Kathleen Friel, PhD

Role: STUDY_DIRECTOR

Burke Medical Research Institute

Locations

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Burke Medical Research Institute

White Plains, New York, United States

Site Status

Countries

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United States

References

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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.

Reference Type BACKGROUND
PMID: 17167918 (View on PubMed)

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.

Reference Type BACKGROUND
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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.

Reference Type BACKGROUND
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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.

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PMID: 18286318 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 9219881 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18421450 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 10080378 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18434014 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 1479394 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18330548 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 12205201 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11459686 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 7529691 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 17702814 (View on PubMed)

Other Identifiers

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BRC391

Identifier Type: -

Identifier Source: org_study_id

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