Altered Connections in the Spinal Cord to Reduce Hand Impairment After Stroke

Stroke Clinical Trial

Official title:

Spinal Plasticity to Reduce Hand Impairment After Stroke

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT03638570
• Other study ID #: Pro00002490
• Status: Not yet recruiting
• Phase: N/A
• Start date: October 2018
• Est. completion date: October 2022

Study information

• Verified date: August 2018
• Source: University of Pittsburgh
• Contact: Debbie Harrington
• Phone: 412-383-1355
• Email: debbie.harrington[@]pitt.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of the study is to induce plasticity in corticospinal-motoneuronal synapses serving an intrinsic hand muscle of the hemiparetic limb in humans with stroke. Neurologically-intact controls are included to verify that an effect was present in absence of stroke. Outcome measures in controls also provide a reference point that help us to understand the size of the effect and mechanisms mediating the effect in the neurologically-intact system.

Description:

Stroke is a leading cause of serious long-term disability in the United States with 795,000 individuals suffering a new or recurrent stroke each year. In most cases, disability is associated with incomplete motor recovery of the paretic limb. Even with intensive therapy, full recovery is often not achieved. Thus, there is a need for mechanistic approaches that drive the impaired neuronal targets of retraining to fully harness the corticospinal system's adaptive capacity.

The goals of this study are to leverage principles of spike timing-dependent plasticity (STDP) via non-invasive stimulation techniques to strengthen corticospinal transmission. Few studies have targeted the cortex after stroke in humans, and none have targeted the corticospinal-motoneuronal synapse in the spinal cord. This study, therefore, is a novel approach to studying neuroplasticity after stroke. Previous work in humans with incomplete spinal cord injury demonstrates that the resulting plasticity transiently enhances motor output, indicating that there is also therapeutic potential.

This study will attempt to induce bi-directional STDP in corticospinal-motoneuronal synapses serving an intrinsic hand muscle of the hemiparetic limb. Control experiments will be completed to provide evidence of the neurophysiological mechanism(s) mediating the effect and to examine behavioral effects.

Individuals who are at least 6 months post first-ever subcortical stroke and have at least partial range of motion of the paretic index finger will be recruited to participate.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 48
• Est. completion date: October 2022
• Est. primary completion date: October 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

INCLUSION CRITERIA

Individuals who have had a stroke:

1. Diagnosis of first ever subcortical stroke

2. At least 6 months after stroke onset

3. Score of 1 or greater on MRC Scale for the FDI muscle

4. Subjects must show an understanding of the study goals and have the ability to follow simple directions as judged by the investigators.

All individuals:

5. Between the ages of 18 and 75 years old

6. U. S. Veterans

EXCLUSION CRITERIA

Individuals who have had a stroke:

1. Hemispatial neglect, aphasia, or cognitive impairment that would impact testing and would interfere with the ability to follow simple instructions, as judged by the investigators

2. Diagnosis of neurological disorder(s) other than stroke influence movement

All individuals:

3. History of seizure or epilepsy

4. Metallic brain implants

5. Implantable cardioverter defibrillators, insulin pumps, or ventriculoperitoneal shunts

6. Pregnant or expecting to become pregnant

7. Difficulty maintaining alertness and/or remaining still.

Related Conditions & MeSH terms

• Central Nervous System Haemorrhage
• Cerebrovascular Accident
• Hemiparesis
• Hemorrhage
• Paresis
• Post-stroke
• Stroke

Intervention

Procedure:
• Stimulation
This study is a novel approach to studying neuroplasticity after stroke. Previous work in humans with incomplete spinal cord injury demonstrates that the resulting plasticity transiently enhances motor output, indicating that there is also therapeutic potential. This study will attempt to induce bi-directional plasticity in corticospinal-motoneuronal synapses serving an intrinsic hand muscle of the hemiparetic limb. Control experiments will be completed to provide evidence of the neurophysiological mechanism(s) mediating the effect and to examine behavioral effects.

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
University of Pittsburgh	US Department of Veterans Affairs

References & Publications (8)

Bunday KL, Perez MA. Motor recovery after spinal cord injury enhanced by strengthening corticospinal synaptic transmission. Curr Biol. 2012 Dec 18;22(24):2355-61. doi: 10.1016/j.cub.2012.10.046. Epub 2012 Nov 29. Erratum in: Curr Biol. 2013 Jan 7;23(1):94. — View Citation

Castel-Lacanal E, Gerdelat-Mas A, Marque P, Loubinoux I, Simonetta-Moreau M. Induction of cortical plastic changes in wrist muscles by paired associative stimulation in healthy subjects and post-stroke patients. Exp Brain Res. 2007 Jun;180(1):113-22. Epub 2007 Jan 31. — View Citation

Castel-Lacanal E, Marque P, Tardy J, de Boissezon X, Guiraud V, Chollet F, Loubinoux I, Moreau MS. Induction of cortical plastic changes in wrist muscles by paired associative stimulation in the recovery phase of stroke patients. Neurorehabil Neural Repair. 2009 May;23(4):366-72. doi: 10.1177/1545968308322841. Epub 2008 Dec 5. — View Citation

Lum PS, Mulroy S, Amdur RL, Requejo P, Prilutsky BI, Dromerick AW. Gains in upper extremity function after stroke via recovery or compensation: Potential differential effects on amount of real-world limb use. Top Stroke Rehabil. 2009 Jul-Aug;16(4):237-53. doi: 10.1310/tsr1604-237. — View Citation

Marsden J, Greenwood R. Physiotherapy after stroke: define, divide and conquer. J Neurol Neurosurg Psychiatry. 2005 Apr;76(4):465-6. — View Citation

Roger VL, Go AS, Lloyd-Jones DM, Benjamin EJ, Berry JD, Borden WB, Bravata DM, Dai S, Ford ES, Fox CS, Fullerton HJ, Gillespie C, Hailpern SM, Heit JA, Howard VJ, Kissela BM, Kittner SJ, Lackland DT, Lichtman JH, Lisabeth LD, Makuc DM, Marcus GM, Marelli A, Matchar DB, Moy CS, Mozaffarian D, Mussolino ME, Nichol G, Paynter NP, Soliman EZ, Sorlie PD, Sotoodehnia N, Turan TN, Virani SS, Wong ND, Woo D, Turner MB; American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics--2012 update: a report from the American Heart Association. Circulation. 2012 Jan 3;125(1):e2-e220. doi: 10.1161/CIR.0b013e31823ac046. Epub 2011 Dec 15. Erratum in: Circulation. 2012 Jun 5;125(22):e1002. — View Citation

Taylor JL, Martin PG. Voluntary motor output is altered by spike-timing-dependent changes in the human corticospinal pathway. J Neurosci. 2009 Sep 16;29(37):11708-16. doi: 10.1523/JNEUROSCI.2217-09.2009. — View Citation

TWITCHELL TE. The restoration of motor function following hemiplegia in man. Brain. 1951 Dec;74(4):443-80. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Corticospinal Transmission (evoked potentials will be recorded via electromyography.)	Different neural elements will be stimulated and evoked potentials will be recorded via electromyography.	12 months
Secondary	Motor Output	The subject will modulate force by holding a force transducer between the paretic index finger and thumb to control the path of a virtual object through targets displayed on a computer monitor. Subjects will modify force applied to transducer in order to align the path of the object through spatial boundaries of ten targets. All ten targets will appear at once. Ten repetitions of the ten targets (orientation of targets changed slightly each time) will be performed. Performance will be quantified by taking the total actual time the object is overlaid with any part of each target, expressed as a percentage of maximum possible time on target.	12 months