Neural Operant Conditioning

Neural Operant Conditioning to Improve Walking After Stroke

The goal of this clinical trial is to learn if operant conditioning can reduce spasticity in order to improve walking in stroke patient. The main questions it aims to answer are:

• Can participants self-regulate reflex excitability
• Can participants self-regulate reflex, reduce spasticity and improve walking Participants will undergo surface stimulation to evoke spinal reflexes and will be asked to control these reflexes therefore reducing spasticity.

Researchers will compare result to able bodied participants to see if [insert effects]

Study Overview

• Status: Recruiting
• Conditions: Stroke; Gait, Hemiplegic; Gait, Spastic; Chronic Stroke; Walking, Difficulty
• Intervention / Treatment: Other: Peripheral Nerve Stimulation

Detailed Description

The study purpose is to investigate the possibility and later effect of spinal reflex self-regulation in post-stroke stiff-knee gait. The intervention will consist of direct current surface stimulation of the peripheral nerves using electrical stimulation. Stimulation will evoke a motor response that will be collected through surface EMG electrodes and processed to depict a measure of the response as feedback to the participant to complete the loop of operant conditioning. The participant will attempt to modulate their responses over multiple sessions to cause this depiction to either increase or decrease its value depending on an established target.

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• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Kristine Hansen, PT; Phone Number: 216-957-3584; Email: khansen1@metrohealth.org

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44109
      • Recruiting
      • MetroHealth Medical Center
      • Contact: Kristine Hansen, PT; Phone Number: 216-957-3584; Email: khansen1@metrohealth.org
      • Principal Investigator: James Sulzer, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Sign and date consent form
2. At least 3 months since stroke event
3. Over 18 years of age at time of eligibility
4. Ability to stand upright and walk for at least 5 minutes
5. Premorbidly independent
6. Mild to moderate gait impairment
7. Reduced knee flexion during walking relative to the unimpaired side
8. Unilateral hemiparesis of the lower limbs
9. Ability to evoke muscle responses through peripheral nerve stimulation, spinal cord stimulation, and transcranial magnetic stimulation
10. Medically stable
11. Skin intact on hemiparetic leg, abdomen, and scalp
12. Ability to evoke muscle responses and/or reflex responses through peripheral nerve stimulation, spinal cord stimulation, and/or transcranial magnetic stimulation

Exclusion Criteria:

1. Co-existing neurological condition other than prior stroke involving the hemiparetic lower limb (e.g., peripheral nerve injury, PD, SCI, TBI, MS).
2. History of lower limb musculoskeletal injury
3. Functionally relevant osteoarthritis and weight bearing restriction
4. Functionally relevant polyneuropathy resulting in lack of sensation in the lower leg
5. Functionally relevant cognitive impairment
6. Functionally relevant vision impairment
7. Pregnant
8. Botox injection to the ipsilateral leg in the last 12 weeks or taking oral anti-spasticity medications
9. Taking part in physical therapy for any walking-related impairment
10. Cardiac pacemaker or other implanted electronic systems
11. Uncontrolled seizure disorder
12. Use of seizure lowering threshold medications and the discretion of the study physician
13. Deficits in communication that interfere with reasonable study participation
14. Severely impaired cognition and communication
15. Severe lower limb pain

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental: Post-stroke Stiff-Knee Gait Participants; Individuals with post-stroke Stiff-Knee gait	Other: Peripheral Nerve Stimulation; Electrical stimulation of peripheral nerves to measure resulting gait kinematics and surface muscle activity

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Surface electromyographic recording of leg muscles	Recording electrical activity of leg muscles during walking in response to peripheral nerve stimulation	baseline, week 6 -mid-treatment, week 12 - end of treatment, 4-week post treatment, 12 weeks post treatment, 24 weeks post treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
10 meter walk test	10 meter walk test with collection of gait kinematics captured using an inertial motion capture camera system	baseline, week 6 -mid-treatment, week 12 - end of treatment, 4-week post treatment, 12 weeks post treatment, 24 weeks post treatment
quadriceps pendulum test	This is a method of evaluating spasticity using gravity to provoke the muscular stretch reflex allowing for the collection of joint angle data. This data will aid in assessing changes in joint angles as a result of training.	baseline, week 6 -mid-treatment, week 12 - end of treatment, 4-week post treatment, 12 weeks post treatment, 24 weeks post treatment
Five Times Sit to Stand Test	measures lower extremity functional strength. This test will measure your leg strength by asking you to sit down and stand up from a chair 5 times as fast as possible.	baseline, week 6 -mid-treatment, week 12 - end of treatment, 4-week post treatment, 12 weeks post treatment, 24 weeks post treatment
TMS	non-invasive brain stimulation device, will be used to elicit a motor evoked response in participants via low frequency stimulation to the cortical regions associated with the muscles being investigated. This approach will test the integrity of the participant's CST in relation to the intervention and assessments being conducted	Baseline, Week 12 - end of treatment

Collaborators and Investigators

• Sponsor: MetroHealth Medical Center
• Investigators: Principal Investigator: James Sulzer, PhD, MetroHealth Medical Center

Publications and helpful links

General Publications

• Li S, Francisco GE. New insights into the pathophysiology of post-stroke spasticity. Front Hum Neurosci. 2015 Apr 10;9:192. doi: 10.3389/fnhum.2015.00192. eCollection 2015.
• Stoquart GG, Detrembleur C, Palumbo S, Deltombe T, Lejeune TM. Effect of botulinum toxin injection in the rectus femoris on stiff-knee gait in people with stroke: a prospective observational study. Arch Phys Med Rehabil. 2008 Jan;89(1):56-61. doi: 10.1016/j.apmr.2007.08.131.
• Thompson AK, Chen XY, Wolpaw JR. Acquisition of a simple motor skill: task-dependent adaptation plus long-term change in the human soleus H-reflex. J Neurosci. 2009 May 6;29(18):5784-92. doi: 10.1523/JNEUROSCI.4326-08.2009.
• Burpee JL, Lewek MD. Biomechanical gait characteristics of naturally occurring unsuccessful foot clearance during swing in individuals with chronic stroke. Clin Biomech (Bristol, Avon). 2015 Dec;30(10):1102-7. doi: 10.1016/j.clinbiomech.2015.08.018. Epub 2015 Sep 2.
• Akbas T, Kim K, Doyle K, Manella K, Lee R, Spicer P, Knikou M, Sulzer J. Rectus femoris hyperreflexia contributes to Stiff-Knee gait after stroke. J Neuroeng Rehabil. 2020 Aug 26;17(1):117. doi: 10.1186/s12984-020-00724-z.
• Li S, Francisco GE, Zhou P. Post-stroke Hemiplegic Gait: New Perspective and Insights. Front Physiol. 2018 Aug 2;9:1021. doi: 10.3389/fphys.2018.01021. eCollection 2018.
• Dehnadi Moghadam A, Hasanzadeh H, Dehnadi Moghadam F. Evaluation of the Effect of Intranasal Lidocaine in the Treatment of Spasticity in Patients with Traumatic Brain Injury. Anesth Pain Med. 2021 Aug 15;11(4):e115849. doi: 10.5812/aapm.115849. eCollection 2021 Aug.
• Navarrete-Opazo AA, Gonzalez W, Nahuelhual P. Effectiveness of Oral Baclofen in the Treatment of Spasticity in Children and Adolescents With Cerebral Palsy. Arch Phys Med Rehabil. 2016 Apr;97(4):604-618. doi: 10.1016/j.apmr.2015.08.417. Epub 2015 Aug 28.
• Wolpaw JR, Braitman DJ, Seegal RF. Adaptive plasticity in primate spinal stretch reflex: initial development. J Neurophysiol. 1983 Dec;50(6):1296-311. doi: 10.1152/jn.1983.50.6.1296.
• Wolpaw JR, Lee CL. Motoneuron response to dorsal root stimulation in anesthetized monkeys after spinal cord transection. Exp Brain Res. 1987;68(2):428-33. doi: 10.1007/BF00248809.
• Chen XY, Wolpaw JR. Operant conditioning of H-reflex in freely moving rats. J Neurophysiol. 1995 Jan;73(1):411-5. doi: 10.1152/jn.1995.73.1.411.

Study record dates

Study Major Dates

• Study Start (Estimated): May 31, 2024
• Primary Completion (Estimated): May 31, 2027
• Study Completion (Estimated): May 31, 2028

Study Registration Dates

• First Submitted: October 23, 2023
• First Submitted That Met QC Criteria: October 27, 2023
• First Posted (Actual): November 2, 2023

Study Record Updates

• Last Update Posted (Actual): November 2, 2023
• Last Update Submitted That Met QC Criteria: October 27, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Stroke; Gait Disorders, Neurologic; Mobility Limitation
• Other Study ID Numbers: StudyID00000301

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No