Back to resultsNeurobiological Principles Applied to the Rehabilitation of Stroke Patients
Primary Purpose
Stroke
Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Transcranial Magnetic Stimulation (TMS)
Carbidopa-Levodopa
Methylphenidate
Amphetamine Sulfate
Placebo
Sham Transcranial Magnetic Stimulation (TMS)
Transcranial Magnetic Stimulation (TMS) Training
Sponsored by
About this trial
This is an interventional treatment trial for Stroke focused on measuring Transcranial Magnetic Stimulation, Rehabilitation, Stroke, Plasticity
Eligibility Criteria
Aims 1 and 2
Inclusion Criteria:
- Normal neurological examination
- Ability to meet criteria of inclusion experiment
- Ability to give informed consent.
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:
Inclusion Criteria:
- 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, 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
Sites / Locations
- Emory University School of Medicine
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
Aim 1
Aim 2
Aim 3
Arm Description
Healthy adult female and male subjects will receive study drugs and TMS training to measure M1 excitability.
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.
Female and male subjects who have experienced a cerebral ischemic infarction, will receive study drugs and TMS to measure M1 excitability.
Outcomes
Primary Outcome Measures
Aim 1: Mean Parameter Estimate for Maximal Motor Evoked Potential (MEPmax) Derived From Stimulus Response Curves (SRC)
Motor evoked potential (MEP) amplitudes were measured prior to treatment (baseline), immediately after the treatment (post-training 1), 30 minutes after the treatment (post-training 2), and 60 minutes after the treatment (post-training 3).The MEP is elicited by transcranial magnetic stimulation (TMS) at increased intensity. Its amplitude is measured from peak to peak and expressed in millivolts (mV). Measured MEP amplitudes were plotted against the intensity to create a stimulus response curve (SRC). SRCs were modeled by a 3- parameter sigmoid function and MEPmax was extracted. Long-lasting increases in MEP amplitude indicate increases in motor cortex excitability and are associated with motor learning.
Aim 1: Mean Peak Acceleration of Wrist Extension Movements
Mean peak acceleration was measured across study drug conditions prior to treatment (baseline), immediately after the treatment (post-training 1), 30 minutes after the treatment (post-training 2) and 60 minutes after the treatment (post-training 3). Increases in the mean peak acceleration of the trained wrist extension movements indicate motor learning. Acceleration was measured in g; a symbol for the average acceleration produced by gravity at the Earth's surface.
Secondary Outcome Measures
Aim 2: Mean Sum of Normalized Motor Evoked Potentials (MEPs) With Respect to Pulse
Mean sum of normalized MEP for repeated TMS (rTMS) conditions with respect to the pulse (-100, +300, placebo, zero) prior to treatment (baseline), immediately after the treatment (post-training 1), 30 minutes after the treatment (post-training 2) and 60 minutes after the treatment (post-training 3). Its amplitude is measured from peak to peak and expressed in mV. Long- lasting increases in MEP amplitude indicate increases in motor cortex excitability and are associated with motor learning.
Aim 2: Mean Peak Acceleration of Wrist Extension Movements With Respect to Pulse
Mean peak acceleration of wrist movements for repeated TMS (rTMS) conditions with respect of the TMS pulse (-100, +300, placebo, zero) prior to treatment (baseline), immediately after the treatment (post-training 1), 30 minutes after the treatment (post-training 2) and 60 minutes after the treatment (post-training 3). Increases in the mean peak acceleration of the trained wrist extension movements indicate motor learning. Acceleration was measured in g; a symbol for the average acceleration produced by gravity at the Earth's surface.
Aim 2: Mean Sum of Normalized Motor Evoked Potentials (MEPs) for rTMS Treatment With Respect to Frequency
Mean sum of normalized MEP for the different frequencies of rTMS treatment (placebo at 0.1 Hz, 0.1 Hz, 0.25 Hz, 0.5 Hz) prior to treatment (baseline), immediately after the treatment (post-training 1), 30 minutes after the treatment (post-training 2) and 60 minutes after the treatment (post-training 3). Increases in the mean peak acceleration of the trained wrist extension movements indicate motor learning.
Aim 2: Mean Peak Acceleration for rTMS Treatment With Respect to Frequency
Mean peak acceleration for the different frequencies of rTMS treatment (placebo, 0.1 Hz, 0.25 Hz, 0.5 Hz) prior to treatment (baseline), immediately after the treatment (post-training 1), 30 minutes after the treatment (post-training 2) and 60 minutes after the treatment (post-training 3). Increases in the mean peak acceleration of the trained wrist extension movements indicate motor learning. Acceleration was measured in g; a symbol for the average acceleration produced by gravity at the Earth's surface.
Aim 3: Mean Parameter Estimate for Maximal Motor Evoked Potential (MEPmax) Derived From Stimulus Response Curves (SRC)
Motor evoked potential (MEP) amplitudes were measured prior to treatment (baseline), immediately after the treatment (post-training 1), 30 minutes after the treatment (post-training 2), and 60 minutes after the treatment (post-training 3).The MEP is elicited by transcranial magnetic stimulation (TMS) at increased intensity. Its amplitude is measured from peak to peak and expressed in millivolts (mV). Measured MEP amplitudes were plotted against the intensity to create a stimulus response curve (SRC). SRCs were modeled by a 3- parameter sigmoid function and MEPmax was extracted. Long-lasting increases in MEP amplitude indicate increases in motor cortex excitability and are associated with motor learning.
Aim 3: Mean Peak Acceleration of Wrist Extension Movements
Mean peak acceleration was measured across study drug conditions prior to treatment (baseline), immediately after the treatment (post-training 1), 30 minutes after the treatment (post-training 2) and 60 minutes after the treatment (post-training 3). Increases in the mean peak acceleration of the trained wrist extension movements indicate motor learning. Acceleration was measured in g; a symbol for the average acceleration produced by gravity at the Earth's surface.
Full Information
NCT ID
NCT00715520
First Posted
July 11, 2008
Last Updated
October 12, 2017
Sponsor
Emory University
Collaborators
National Institutes of Health (NIH), National Institute of Neurological Disorders and Stroke (NINDS)
1. Study Identification
Unique Protocol Identification Number
NCT00715520
Brief Title
Neurobiological Principles Applied to the Rehabilitation of Stroke Patients
Official Title
Neurobiological Principles Applied to the Rehabilitation of Stroke Patients
Study Type
Interventional
2. Study Status
Record Verification Date
October 2017
Overall Recruitment Status
Completed
Study Start Date
April 2007 (undefined)
Primary Completion Date
September 2016 (Actual)
Study Completion Date
September 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Emory University
Collaborators
National Institutes of Health (NIH), National Institute of Neurological Disorders and Stroke (NINDS)
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Stroke
Keywords
Transcranial Magnetic Stimulation, Rehabilitation, Stroke, Plasticity
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Factorial Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
33 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Aim 1
Arm Type
Experimental
Arm Description
Healthy adult female and male subjects will receive study drugs and TMS training to measure M1 excitability.
Arm Title
Aim 2
Arm Type
Experimental
Arm Description
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.
Arm Title
Aim 3
Arm Type
Experimental
Arm Description
Female and male subjects who have experienced a cerebral ischemic infarction, will receive study drugs and TMS to measure M1 excitability.
Intervention Type
Other
Intervention Name(s)
Transcranial Magnetic Stimulation (TMS)
Intervention Description
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
Drug
Intervention Name(s)
Carbidopa-Levodopa
Other Intervention Name(s)
Sinemet
Intervention Description
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
Intervention Name(s)
Methylphenidate
Intervention Description
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
Intervention Name(s)
Amphetamine Sulfate
Intervention Description
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
Intervention Name(s)
Placebo
Intervention Description
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
Other
Intervention Name(s)
Sham Transcranial Magnetic Stimulation (TMS)
Intervention Description
Sham TMS pulses will be randomly administered during TMS sessions.
Intervention Type
Other
Intervention Name(s)
Transcranial Magnetic Stimulation (TMS) Training
Intervention Description
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.
Primary Outcome Measure Information:
Title
Aim 1: Mean Parameter Estimate for Maximal Motor Evoked Potential (MEPmax) Derived From Stimulus Response Curves (SRC)
Description
Motor evoked potential (MEP) amplitudes were measured prior to treatment (baseline), immediately after the treatment (post-training 1), 30 minutes after the treatment (post-training 2), and 60 minutes after the treatment (post-training 3).The MEP is elicited by transcranial magnetic stimulation (TMS) at increased intensity. Its amplitude is measured from peak to peak and expressed in millivolts (mV). Measured MEP amplitudes were plotted against the intensity to create a stimulus response curve (SRC). SRCs were modeled by a 3- parameter sigmoid function and MEPmax was extracted. Long-lasting increases in MEP amplitude indicate increases in motor cortex excitability and are associated with motor learning.
Time Frame
Baseline, Post-Training 1 (Immediately), Post-Training 2 (30 Minutes), Post-Training 3 (60 Minutes)
Title
Aim 1: Mean Peak Acceleration of Wrist Extension Movements
Description
Mean peak acceleration was measured across study drug conditions prior to treatment (baseline), immediately after the treatment (post-training 1), 30 minutes after the treatment (post-training 2) and 60 minutes after the treatment (post-training 3). Increases in the mean peak acceleration of the trained wrist extension movements indicate motor learning. Acceleration was measured in g; a symbol for the average acceleration produced by gravity at the Earth's surface.
Time Frame
Baseline, Post-Training 1 (Immediately), Post-Training 2 (30 Minutes), Post-Training 3 (60 Minutes)
Secondary Outcome Measure Information:
Title
Aim 2: Mean Sum of Normalized Motor Evoked Potentials (MEPs) With Respect to Pulse
Description
Mean sum of normalized MEP for repeated TMS (rTMS) conditions with respect to the pulse (-100, +300, placebo, zero) prior to treatment (baseline), immediately after the treatment (post-training 1), 30 minutes after the treatment (post-training 2) and 60 minutes after the treatment (post-training 3). Its amplitude is measured from peak to peak and expressed in mV. Long- lasting increases in MEP amplitude indicate increases in motor cortex excitability and are associated with motor learning.
Time Frame
Baseline, Post-Training 1(Immediately), Post-Training 2 (30 Minutes), Post-Training 3 (60 Minutes)
Title
Aim 2: Mean Peak Acceleration of Wrist Extension Movements With Respect to Pulse
Description
Mean peak acceleration of wrist movements for repeated TMS (rTMS) conditions with respect of the TMS pulse (-100, +300, placebo, zero) prior to treatment (baseline), immediately after the treatment (post-training 1), 30 minutes after the treatment (post-training 2) and 60 minutes after the treatment (post-training 3). Increases in the mean peak acceleration of the trained wrist extension movements indicate motor learning. Acceleration was measured in g; a symbol for the average acceleration produced by gravity at the Earth's surface.
Time Frame
Baseline, Post-Training 1(Immediately), Post-Training 2 (30 Minutes), Post-Training 3 (60 Minutes)
Title
Aim 2: Mean Sum of Normalized Motor Evoked Potentials (MEPs) for rTMS Treatment With Respect to Frequency
Description
Mean sum of normalized MEP for the different frequencies of rTMS treatment (placebo at 0.1 Hz, 0.1 Hz, 0.25 Hz, 0.5 Hz) prior to treatment (baseline), immediately after the treatment (post-training 1), 30 minutes after the treatment (post-training 2) and 60 minutes after the treatment (post-training 3). Increases in the mean peak acceleration of the trained wrist extension movements indicate motor learning.
Time Frame
Baseline, Post-Training 1(Immediately), Post-Training 2 (30 Minutes), Post-Training 3 (60 Minutes)
Title
Aim 2: Mean Peak Acceleration for rTMS Treatment With Respect to Frequency
Description
Mean peak acceleration for the different frequencies of rTMS treatment (placebo, 0.1 Hz, 0.25 Hz, 0.5 Hz) prior to treatment (baseline), immediately after the treatment (post-training 1), 30 minutes after the treatment (post-training 2) and 60 minutes after the treatment (post-training 3). Increases in the mean peak acceleration of the trained wrist extension movements indicate motor learning. Acceleration was measured in g; a symbol for the average acceleration produced by gravity at the Earth's surface.
Time Frame
Baseline, Post-Training 1(Immediately), Post-Training 2 (30 Minutes), Post-Training 3 (60 Minutes)
Title
Aim 3: Mean Parameter Estimate for Maximal Motor Evoked Potential (MEPmax) Derived From Stimulus Response Curves (SRC)
Description
Motor evoked potential (MEP) amplitudes were measured prior to treatment (baseline), immediately after the treatment (post-training 1), 30 minutes after the treatment (post-training 2), and 60 minutes after the treatment (post-training 3).The MEP is elicited by transcranial magnetic stimulation (TMS) at increased intensity. Its amplitude is measured from peak to peak and expressed in millivolts (mV). Measured MEP amplitudes were plotted against the intensity to create a stimulus response curve (SRC). SRCs were modeled by a 3- parameter sigmoid function and MEPmax was extracted. Long-lasting increases in MEP amplitude indicate increases in motor cortex excitability and are associated with motor learning.
Time Frame
Baseline, Post-Training 1(Immediately), Post-Training 2 (30 Minutes), Post-Training 3 (60 Minutes)
Title
Aim 3: Mean Peak Acceleration of Wrist Extension Movements
Description
Mean peak acceleration was measured across study drug conditions prior to treatment (baseline), immediately after the treatment (post-training 1), 30 minutes after the treatment (post-training 2) and 60 minutes after the treatment (post-training 3). Increases in the mean peak acceleration of the trained wrist extension movements indicate motor learning. Acceleration was measured in g; a symbol for the average acceleration produced by gravity at the Earth's surface.
Time Frame
Baseline, Post-Training 1(Immediately), Post-Training 2 (30 Minutes), Post-Training 3 (60 Minutes)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Aims 1 and 2
Inclusion Criteria:
Normal neurological examination
Ability to meet criteria of inclusion experiment
Ability to give informed consent.
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:
Inclusion Criteria:
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, 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Cathrin M Buetefisch, MD
Organizational Affiliation
Emory University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Emory University School of Medicine
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Neurobiological Principles Applied to the Rehabilitation of Stroke Patients
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