Neurobiological Principles Applied to the Rehabilitation of Stroke Patients

NCT ID: NCT00715520

Last Updated: 2017-10-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 33 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-04-30
• Study Completion Date: 2016-09-30

Brief Summary

The purpose of this study is to use (Transcranial Magnetic Stimulation) TMS or drugs to improve learning of movement skills and the adaptation processes in patients after stroke. Once investigators have determined the improving effect of TMS and the drugs on learning of movement skills, the study team may be able to provide information that improves rehabilitative treatment and helps to improve recovery after stroke.

Detailed Description

Previous studies have shown, that when patients learn a new motor movement, it may cause a change in the way the nerves act in the area of the brain that controls movement. This change is called use-dependent plasticity. The ability of that part of the brain, called the motor cortex (M1), to reorganize plays a major role in the recovery of motor deficits post-stroke; hence the importance for further development of rehabilitative strategies that utilize this potential for recovery. In this proposed study, investigators will further examine influences of use-dependent plasticity in the non-injured M1 of healthy subjects and injured M1 of stroke subjects using a combination of non-invasive cortical stimulation, medication, and exercise techniques. In Aim 1, investigators will test the effect of drugs that interact specifically with different neurotransmitter systems on use-dependent plasticity in intact M1 of healthy humans. In Aim 2, investigators will identify the parameters for non-invasive transcranial magnetic stimulation (TMS) of M1 that are most effective to enhance use-dependent plasticity in intact healthy human M1. In Aim 3, investigators will test the drugs and rTMS protocols that were demonstrated to be most effective to enhance use- dependent plasticity in the Specific Aim 1 and 2 and apply them to participants who have experienced a stroke. Results from this study will help to inform future research about the efficacy of plasticity enhancing methods in injured M1 of stroke patients.

Conditions

Stroke

Keywords

Transcranial Magnetic Stimulation; Rehabilitation; Stroke; Plasticity

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Aim 1

Healthy adult female and male subjects will receive study drugs and TMS training to measure M1 excitability.

Group Type: EXPERIMENTAL

Carbidopa-Levodopa

Intervention Type: DRUG

Participants will receive one oral dose of carbidopa-levodopa 25mg one hour prior to measuring wrist extension movements.

The order in which Carbidopa-Levodopa is given will be randomized per participant.

Methylphenidate

Intervention Type: DRUG

Participants will receive one oral dose of methylphenidate 40mg 2 hours prior to measuring wrist extension movements.

The order in which Methylphenidate is given will be randomized per participant.

Amphetamine Sulfate

Intervention Type: DRUG

Participants will receive one oral dose of amphetamine sulfate 10mg 2 hours prior to measuring wrist extension movements.

The order in which Amphetamine Sulfate is given will be randomized per participant.

Placebo

Intervention Type: DRUG

Participants will receive one oral tablet of placebo 2 hours prior to measuring wrist extension movements.

The order in which Placebo is given will be randomized per participant.

Transcranial Magnetic Stimulation (TMS) Training

Intervention Type: OTHER

TMS surface electromyographic activity will be recorded with surface electrodes mounted on the skin overlaying a forearm muscle. Single pulses of TMS at increasing intensity will be delivered to measure motor cortex excitability. Peak acceleration and TMS evoked responses in the muscle will be measured prior to the training, after completion of the training and again one hour after completion of the training.

Aim 2

Healthy adult female and male subjects will receive repetitive TMS (rTMS) at different times or frequencies with respect to the training movement or sham stimulation.

Group Type: EXPERIMENTAL

Transcranial Magnetic Stimulation (TMS)

Intervention Type: OTHER

Each TMS training session will begin with a baseline measurement lasting about 30 minutes in which brief magnetic pulses will be generated by the single-pulse and paired pulse TMS stimulator and the responses are recorded with surface EMG electrodes. Participants will be instructed to move their wrist for up to ½ hour. After these measures, rTMS will be applied to the scalp during training. Stimulation will occur at a low rate of different frequencies and different times with respect to the training movement depending on the experimental condition. In the last phase of the session post-training measurements will be done using single TMS pulses. TMS pulses and intensity with be given in random order.

Sham Transcranial Magnetic Stimulation (TMS)

Intervention Type: OTHER

Sham TMS pulses will be randomly administered during TMS sessions.

Aim 3

Female and male subjects who have experienced a cerebral ischemic infarction, will receive study drugs and TMS to measure M1 excitability.

Group Type: EXPERIMENTAL

Carbidopa-Levodopa

Intervention Type: DRUG

Participants will receive one oral dose of carbidopa-levodopa 25mg one hour prior to measuring wrist extension movements.

The order in which Carbidopa-Levodopa is given will be randomized per participant.

Methylphenidate

Intervention Type: DRUG

Participants will receive one oral dose of methylphenidate 40mg 2 hours prior to measuring wrist extension movements.

The order in which Methylphenidate is given will be randomized per participant.

Amphetamine Sulfate

Intervention Type: DRUG

Participants will receive one oral dose of amphetamine sulfate 10mg 2 hours prior to measuring wrist extension movements.

The order in which Amphetamine Sulfate is given will be randomized per participant.

Placebo

Intervention Type: DRUG

Participants will receive one oral tablet of placebo 2 hours prior to measuring wrist extension movements.

The order in which Placebo is given will be randomized per participant.

Sham Transcranial Magnetic Stimulation (TMS)

Intervention Type: OTHER

Sham TMS pulses will be randomly administered during TMS sessions.

Transcranial Magnetic Stimulation (TMS) Training

Intervention Type: OTHER

TMS surface electromyographic activity will be recorded with surface electrodes mounted on the skin overlaying a forearm muscle. Single pulses of TMS at increasing intensity will be delivered to measure motor cortex excitability. Peak acceleration and TMS evoked responses in the muscle will be measured prior to the training, after completion of the training and again one hour after completion of the training.

Interventions

Transcranial Magnetic Stimulation (TMS)

Each TMS training session will begin with a baseline measurement lasting about 30 minutes in which brief magnetic pulses will be generated by the single-pulse and paired pulse TMS stimulator and the responses are recorded with surface EMG electrodes. Participants will be instructed to move their wrist for up to ½ hour. After these measures, rTMS will be applied to the scalp during training. Stimulation will occur at a low rate of different frequencies and different times with respect to the training movement depending on the experimental condition. In the last phase of the session post-training measurements will be done using single TMS pulses. TMS pulses and intensity with be given in random order.

Intervention Type: OTHER

Carbidopa-Levodopa

Participants will receive one oral dose of carbidopa-levodopa 25mg one hour prior to measuring wrist extension movements.

The order in which Carbidopa-Levodopa is given will be randomized per participant.

Intervention Type: DRUG

Methylphenidate

Participants will receive one oral dose of methylphenidate 40mg 2 hours prior to measuring wrist extension movements.

The order in which Methylphenidate is given will be randomized per participant.

Intervention Type: DRUG

Amphetamine Sulfate

Participants will receive one oral dose of amphetamine sulfate 10mg 2 hours prior to measuring wrist extension movements.

The order in which Amphetamine Sulfate is given will be randomized per participant.

Intervention Type: DRUG

Placebo

Participants will receive one oral tablet of placebo 2 hours prior to measuring wrist extension movements.

The order in which Placebo is given will be randomized per participant.

Intervention Type: DRUG

Sham Transcranial Magnetic Stimulation (TMS)

Sham TMS pulses will be randomly administered during TMS sessions.

Intervention Type: OTHER

Transcranial Magnetic Stimulation (TMS) Training

TMS surface electromyographic activity will be recorded with surface electrodes mounted on the skin overlaying a forearm muscle. Single pulses of TMS at increasing intensity will be delivered to measure motor cortex excitability. Peak acceleration and TMS evoked responses in the muscle will be measured prior to the training, after completion of the training and again one hour after completion of the training.

Intervention Type: OTHER

Other Intervention Names

Sinemet

Eligibility Criteria

Inclusion Criteria

• Normal neurological examination
• Ability to meet criteria of inclusion experiment
• Ability to give informed consent.

• Cerebral ischemic infarction more than 6 months prior to entering the study
• Single lesion as defined by MRI of the brain affecting the primary motor output system of the hand at a cortical (M1) level or subcortical level, or unilateral, and supratentorial in absence of history of a previous symptomatic stroke within 3 months of the current stroke
• Dense paresis of the hand for more than three days after cerebral infarction (MRC of < 4- of wrist- and finger extension/flexion movements)
• Good functional recovery of hand function as defined by MRC of 4 or 4+ of wrist- and finger extension/flexion movements
• Ability to perform wrist extension movements
• Ability to meet criteria of inclusion experiment
• Ability to give informed consent
• Ability of TMS to elicit a measurable MEP of > 100 μV and an increase in MEP amplitude with increasing stimulus intensity (up to 100% of MSO) of at least 20% over MEP amplitude at MT

Exclusion Criteria

• History or neurological or psychiatric disease
• Abnormal MRI of brain
• Abnormal neuropsychological testing
• Intake of CNS active drugs
• History of seizure disorder
• History of migraine headaches
• History of anaphylaxis or allergic reactions
• Contraindication to TMS

Aim 3:

• History or neurological or psychiatric disease, including bipolar disorder
• Intake of CNS active drugs
• History of seizure disorder
• History of migraine headaches
• History of anaphylaxis or allergic reactions
• Contraindication to TMS

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institutes of Health (NIH)

NIH

Sponsor Role: collaborator

National Institute of Neurological Disorders and Stroke (NINDS)

NIH

Sponsor Role: collaborator

Emory University

OTHER

Sponsor Role: lead

Responsible Party

Cathrin Buetefisch

Dr. Cathrin Buetefisch

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Cathrin M Buetefisch, MD

Role: PRINCIPAL_INVESTIGATOR

Emory University

Locations

Emory University School of Medicine

Atlanta, Georgia, United States

Countries

United States

Other Identifiers

R01NS060830-01A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NPARR01

Identifier Type: OTHER

Identifier Source: secondary_id

IRB00046953

Identifier Type: -

Identifier Source: org_study_id